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Abstract Although the metabolism of yolk lipids such as docosahexaenoic acid (DHA) is pivotal for embryonic development, the underlying mechanism remains elusive. Here we find that the zebrafish hydroxysteroid (17-β) dehydrogenase 12a (hsd17b12a), which encodes an intestinal epithelial-specific enzyme, is essential for the biosynthesis of long-chain polyunsaturated fatty acids in primitive intestine of larval fish. The deficiency of hsd17b12a leads to severe developmental defects in the primitive intestine and exocrine pancreas. Mechanistically, hsd17b12a deficiency interrupts DHA synthesis from essential fatty acids derived from yolk-deposited triglycerides, and consequently disrupts the intestinal DHA-phosphatidic acid (PA)-phosphatidylglycerol (PG) axis. This ultimately results in developmental defects of digestive organs, primarily driven by ferroptosis. Our findings indicate that the DHA-PA-PG axis in the primitive intestine facilitates the uptake of yolk lipids and promotes the expansion of digestive organs, thereby uncovering a mechanism through which DHA regulates embryonic development.

Highlights Nonflammable gel polymer electrolyte (SGPE) is developed by in situ polymerizing trifluoroethyl methacrylate (TFMA) monomers with flame-retardant triethyl phosphate (TEP) solvents and LiTFSI–LiDFOB dual lithium salts. Molecular polarity interaction between TEP and PTFMA mitigates interfacial reactions and changes the solvation of Li+. SGPE forms stable inorganic-rich solid electrolyte interface/cathode electrolyte interface layer, exhibiting well compatibility with Li anode and LiCoO2-type high-voltage cathode.

Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized primarily by cognitive impairment. The motivation of this paper is to explore the impact of the visual information transmission pathway (V–H pathway) on AD, and the following feature were observed: Hemoglobin expression on the V–H pathway becomes dysregulated as AD occurs so as to the pathway becomes dysfunctional. According to the feature, the following conclusion was proposed: As AD occurs, abnormal tau proteins penetrate bloodstream and arrive at the brain regions of the pathway. Then the tau proteins or other toxic substances attack hemoglobin molecules. Under the attack, hemoglobin expression becomes more dysregulated. The dysfunction of V–H pathway has an impact on early symptoms of AD, such as spatial recognition disorder and face recognition disorder.

Abstract Background Although sorafenib has been consistently used as a first-line treatment for advanced hepatocellular carcinoma (HCC), most patients will develop resistance, and the mechanism of resistance to sorafenib needs further study. Methods Using KAS-seq technology, we obtained the ssDNA profiles within the whole genome range of SMMC-7721 cells treated with sorafenib for differential analysis. We then intersected the differential genes obtained from the analysis of hepatocellular carcinoma patients in GSE109211 who were ineffective and effective with sorafenib treatment, constructed a PPI network, and obtained hub genes. We then analyzed the relationship between the expression of these genes and the prognosis of hepatocellular carcinoma patients. Results In this study, we identified 7 hub ERGs (ACTB, CFL1, ACTG1, ACTN1, WDR1, TAGLN2, HSPA8) related to drug resistance, and these genes are associated with the cytoskeleton. Conclusions The cytoskeleton is associated with sorafenib resistance in hepatocellular carcinoma. Using KAS-seq to analyze the early changes in tumor cells treated with drugs is feasible for studying the drug resistance of tumors, which provides reference significance for future research.

Carbon nanotubes (CNTs) reinforced cement based grouting material is an important part of green manufacturing industry. Our previous research showed that this material can effectively enhance the impact resistance of rock matrix. In this study, We conducted a comprehensive study and quantitative analysis of the changes in pore structure of this material under impact conditions. Dynamic impact testing and computed tomography (CT) revealed that CNTs significantly increased the cement content in the sample by 79.11 %. The CNTs group exhibited higher internal pore density and uniformity, effectively suppressing the formation of dynamic cracks in the sample. Compared to Non-carbon nanotubes (Non-CNTs) cement-based materials, the peak dynamic stress of the CNTs group increased by 4.76–21.54 %, while the porosity decreased by 57.26 %.This study further refined the enhancement behaviors of carbon nanotubes reinforced cement based, and making outstanding contributions to engineering practice.

Introduction: The herbal formula Chouchunpi San (CCPS) is a traditional formula that has been widely used and proven effective in various clinical cancer treatments. However, the mechanism of its anticancer effect remains unclear. This study aims to determine the anti-tumor effect of CCPS on colorectal cancer (CRC) in vivo and in vitro and to explore the underlying molecular mechanisms. Methods: Cell counting kit-8 assays, colony-forming assays, and flow cytometry for cell cycle and apoptosis assays were employed to determine the anti-tumor roles of CCPS. Liquid chromatography-mass spectrometry (LC-MS), network pharmacology, molecular docking, analysis of real-world clinical datasets of CRC, and western blotting were conducted to explore the molecular mechanism of CCPS on CRC. CRC xenografted mouse model, western blotting, and public CRC data analysis were conducted to evaluate the anti-tumor efficacy and mechanisms of CCPS on CRC. Results: CCPS suppresses the growth of CRC cells and increases the number of apoptotic cells dose-dependently. CCPS targets and significantly downregulates RPA1 and enhances the phosphorylation of its downstream effectors, ATR and CHK1, which are critical for CRC progression. Additionally, CCPS shows a comparable anti-tumor effect in CRC xenografted mouse models compared to Capecitabine, a chemotherapy drug commonly used in clinics. Discussion: Our findings demonstrate the potential use of CCPS in cancer treatment by suppressing cancer cell growth and modulating the RPA1/ATR/CHK1 signaling pathway in CRC. Further investigations on the application of CCPS in cancer therapies could be extended to evaluate the potential in vivo toxicity and adverse events, as well as the synergistic effect of CCPS in combination with other chemotherapeutic agents.

In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy (on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβ bond cleavage induced by electrochemical oxidations.

The regulatory mechanism of gonadal sex differentiation, which is complex and regulated by multiple factors, remains poorly understood in teleosts. Recently, we have shown that compromised androgen and estrogen synthesis with increased progestin leads to all-male differentiation with proper testis development and spermatogenesis in cytochrome P450 17a1 (cyp17a1)-/- zebrafish. In the present study, the phenotypes of female-biased sex ratio were positively correlated with higher Fanconi anemia complementation group L (fancl) expression in the gonads of doublesex and mab-3 related transcription factor 1 (dmrt1)-/- and cyp17a1-/-;dmrt1-/- fish. The additional depletion of fancl in cyp17a1-/-;dmrt1-/- zebrafish reversed the gonadal sex differentiation from all-ovary to all-testis (in cyp17a1-/-;dmrt1-/-;fancl-/- fish). Luciferase assay revealed a synergistic inhibitory effect of Dmrt1 and androgen signaling on fancl transcription. Furthermore, an interaction between Fancl and the apoptotic factor Tumour protein p53 (Tp53) was found in vitro. The interaction between Fancl and Tp53 was observed via the WD repeat domain (WDR) and C-terminal domain (CTD) of Fancl and the DNA binding domain (DBD) of Tp53, leading to the K48-linked polyubiquitination degradation of Tp53 activated by the ubiquitin ligase, Fancl. Our results show that testis fate in cyp17a1-/- fish is determined by Dmrt1, which is thought to stabilize Tp53 by inhibiting fancl transcription during the critical stage of sexual fate determination in zebrafish.

The study of formation pressure holds great significance for both exploration and development. The formation pressure coefficient is a crucial parameter in geology, encompassing various aspects. Numerous models exist to explore its influencing factors, yet they remain highly controversial. Our research has gathered data on formation pressure states and tectonic movement rates from dozens of large sedimentary basins worldwide. We delved into the patterns of formation pressure changes during basin deposition, subsidence, and tectonic uplift, taking into account the permeability of formation water. The findings reveal that during the Neogene and beyond, rapid deposition or tectonic uplift can cause the infiltration of formation water to lag behind tectonic movements, resulting in overpressure. Conversely, if recent tectonic movements are slow, formation water will complete its infiltration process ahead of tectonic changes, bringing the formation pressure to a hydrostatic state. Consequently, we have concluded that abnormal formation pressure primarily depends on the rate of tectonic movements during the Neogene and Quaternary periods. This study also proposes four formation pressure models, paving the way for a comprehensive understanding of formation pressure within a unified theoretical framework.

Cultivated beet (Beta vulgaris L. ssp. vulgaris) originated from sea beet (B. vulgaris ssp. maritima (L.) Arcang), a wild beet species widely distributed along the coasts of the Mediterranean Sea and Atlantic Ocean, as well as northern Africa. Understanding the evolution of sea beet will facilitate its efficient use in sugarbeet improvement. We used SNPs (single nucleotide polymorphisms) covering the whole genome to analyze 599 sea beet accessions collected from the north Atlantic Ocean and Mediterranean Sea coasts. All B. maritima accessions can be grouped into eight clusters with each corresponding to a specific geographic region. Clusters 2, 3 and 4 with accessions mainly collected from Mediterranean coasts are genetically close to each other as well as to Cluster 6 that contained mainly cultivated beet. Other clusters were relatively distinct from cultivated beets with Clusters 1 and 5 containing accessions from north Atlantic Ocean coasts, Clusters 7 and Cluster 8 mainly have accessions from northern Egypt and southern Europe, and northwest Morocco, respectively. Distribution of B. maritima subpopulations aligns well with the direction of marine currents that was considered a main dynamic force in spreading B. maritima during evolution. Estimation of genetic diversity indices supported the formation of B. maritima subpopulations due to local genetic drift, historic migration, and limited gene flow. Our results indicated that B. maritima originated from southern Europe and then spread to other regions through marine currents to form subpopulations. This research provides vital information for conserving, collecting, and utilizing wild sea beet to sustain sugarbeet improvement.

Summary: Functions of the SKP1-CUL1-F box (SCF) ubiquitin E3 ligases are essential in plants. The F box proteins (FBPs) are substrate receptors that recruit substrates and assemble an active SCF complex, but the regulatory mechanism underlying the FBPs binding to CUL1 to activate the SCF cycle is not fully understood. We show that Arabidopsis csn1-10 is defective in SCFEBF1-mediated PIF3 degradation during de-etiolation, due to impaired association of EBF1 with CUL1 in csn1-10. EBF1 preferentially associates with un-neddylated CUL1 that is deficient in csn1-10 and the EBF1-CUL1 binding is rescued by the neddylation inhibitor MLN4924. Furthermore, we identify a subset of FBPs with impaired binding to CUL1 in csn1-10, indicating their assembly to form SCF complexes may depend on COP9 signalosome (CSN)-mediated deneddylation of CUL1. This study reports that a key role of CSN-mediated CULLIN deneddylation is to gate the binding of the FBP-substrate module to CUL1, thus initiating the SCF cycle of substrate ubiquitination.

To study the creep minor damage evolution process and creep damage mechanism of mudstone, this paper establishes a numerical model of a two-media triple cementation particle flow procedure of mudstone, reproduces the tender damage destruction process of mudstone under creep based on a parallel bonded stress corrosion model, and explores the macroscopic creep characteristics and minor damage mechanism of mudstone specimens under different stress levels and surrounding pressure conditions. The results show that the intrinsic driving force for creep damage in mudstone is the micro-tensile force generated between non-homogeneous particles of mudstone, and the inter-particle cementation is continuously damaged and deteriorated with increasing time; the stable creep rate of mudstone specimens increases with increasing stress level and decreases with increasing surrounding pressure; high-stress levels diffuse microscopic damage in mudstone by increasing the magnitude of inter-particle microtension and the number of particles generating microtension, manifesting as multiple extensions of microcracks; the enclosing pressure dramatically reduces the creep characteristics by limiting the development of inter-particle micro-tensile forces; the microcrack distribution is more uniform and dispersed under the enclosing pressure conditions. The amount of mutual slip between particles increases.

As one of the three major components of woody biomass, lignin is a kind of natural organic polymer and the only abundant natural renewable resource with aromatic nucleus. Chemical catalysis induced depolymerization is an important and effective approach for lignin utilization. In particular, photocatalysis and electrocatalysis show great potential in accurately activating C–O/C–C bonds, which is a critical point of selective cleavage of lignin. In this contribution, we focus on radical and (photo)electron transfer induced reaction mechanisms of the photo(electro)catalytic depolymerization of lignin. Primarily, the general situation of Carbon-centered radicals and active oxygen species mediated lignin conversion has been discussed. Then the mechanisms for (photo)electron transfer mediated lignin depolymerization have been summarized. At the end of this review, the challenges and opportunities of photo(electro)catalysis in the applications of lignin valorization have been forecasted.

Abstract The reaction efficiency of reactants near plasmonic nanostructures can be enhanced significantly because of plasmonic effects. Herein, we propose that the catalytic activity of molecular catalysts near plasmonic nanostructures may also be enhanced dramatically. Based on this proposal, we develop a highly efficient and stable photocatalytic system for the hydrogen evolution reaction (HER) by compositing a molecular catalyst of cobalt porphyrin together with plasmonic gold nanoparticles, around which plasmonic effects of localized electromagnetic field, local heating, and enhanced hot carrier excitation exist. After optimization, the HER rate and turn-over frequency (TOF) reach 3.21 mol g−1 h−1 and 4650 h−1, respectively. In addition, the catalytic system remains stable after 45-hour catalytic cycles, and the system is catalytically stable after being illuminated for two weeks. The enhanced reaction efficiency is attributed to the excitation of localized surface plasmon resonance, particularly plasmon-generated hot carriers. These findings may pave a new and convenient way for developing plasmon-based photocatalysts with high efficiency and stability.

Against the background of the prevailing green development paradigm, numerous coal mines have embraced the adoption of gob-side entry retaining mining technology. The most commonly employed form of gob-side entry retaining involves building an artificial wall along the edge of the goaf behind the working face to maintain the roadway. The pivotal challenge in gob-side entry retaining lies in the roadside support. Currently, commonplace concrete serves as the predominant material for the roadside filling body. Nevertheless, traditional concrete exhibits drawbacks, including inadequate tensile strength and poor toughness, leading to wall cracks or even collapses in the retaining wall. Steel fiber, a frequently employed reinforcement and toughening agent in concrete, has found widespread application in the construction sector and other fields. However, its use as a roadside filling material in underground coal mines remains infrequent. Therefore, in this paper, the flow and mechanical properties of steel fiber concrete were tested and analyzed, and field industrial tests were conducted. Results of indoor experiments show that steel fibers reduce the slump of concrete. The addition of steel fibers shifted the pore compacting stage, linear elasticity stage, and destabilization stage forward and improved the post-peak bearing capacity. The addition of steel fibers makes the concrete compressive and tensile strength show a “first increase and then decrease” trend; both peaked at 1.5%, and the increase in tensile strength is more pronounced. Steel fibers enhance the strength of compressive strength of concrete at an early age, weaker at a late age, and tensile strength inversely. The addition of steel fiber can change the concrete matrix from tensile damage to shear damage, and the toughness index shows the trend of “first increase and then decrease”, and reaches the peak value when the dosage is 1.5%. Industrial test results show that steel fiber concrete as a roadside filling body can reduce the surrounding rock surface displacement and bolt (cable) force.

IntroductionSclerotinia sclerotiorum is a serious pathogen causing severe basal stalk rot (BSR) disease on cultivated sunflower (Helianthus annuus L.) that leads to significant yield losses due to insufficient resistance. The wild annual sunflower species H. petiolaris, commonly known as prairie sunflower is known for its resistance against this pathogen. Sunflower resistance to BSR is quantitative and determined by many genes with small effects on the resistance phenotype. The objective of this study was to identify loci governing BSR resistance derived from H. petiolaris using a quantitative trait loci (QTL) mapping approach.MethodsBSR resistance among lines of an advanced backcross population (AB-QTL) with 174 lines developed from a cross of inbred line HA 89 with H. petiolaris PI 435843 was determined in the field during 2017-2019, and in the greenhouse in 2019. AB-QTL lines and the HA 89 parent were genotyped using genotyping-by-sequencing and a genetic linkage map was developed spanning 997.51 cM and using 1,150 SNP markers mapped on 17 sunflower chromosomes.Results and discussionHighly significant differences (p

Rational design and facile preparation of low-cost and efficient catalysts for the selective converting of biomass-derived monosaccharides into high value-added chemicals is highly demanded, yet challenging. Herein, we first demonstrate a N doped defect-rich carbon (NC-800-5) as metal-free catalyst for the selective oxidation of d-xylose into d-xylonic acid in alkaline aqueous solution at 100 °C for 30 min, with 57.4% yield. The doped graphitic N is found to be the active site and hydroxyl ion participating in the oxidation of d-xylose. Hydroxyl ion and d-xylose first adsorb on NC-800-5 surface, and the aldehyde group of d-xylose is catalyzed to form germinal diols ion. Then, C–H bond break to yield carboxylic group. Furthermore, NC-800-5 catalyst shows high stability in recycled test.

Ionic liquids (ILs) have attracted increasing attention since last few decades due to their high molecular design abilities and wide applications in different fields. In this study, four novel fluorescent isoquinolino [2,1-a]quinoxalin-5-ium ILs were designed and synthesized via a two-step process including a simple dual Schiff's base formation and a subsequent [RhCp∗Cl2]2-catalyzed oxidative C–H activation/annulation reaction. The as-synthesized ILs were extensively characterized using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR, HSQC-NMR, HMBC-NMR and HR-MS. Their photophysical properties were determined by steady-state fluorescence spectroscopy. The results demonstrate that all these ILs showed dual or triple emissions, large stokes shift (90 nm) and mechanochromic behaviors. Basing on solvatochromism and titration experiments, it is thought that the emission bands of the ILs are raised from their local excited states, charge transfer states or excited state proton transfer of cations, while the substitute effect of these quinoxaline derived ILs on their stokes shifts is negligible.

Abstract Exosomes mediate intercellular communication by transmitting active molecules. The function of long noncoding RNA (lncRNA) H19 in autoimmune liver injury is unclear. Concanavalin A (ConA)‐induced liver injury is well‐characterized immune‐mediated hepatitis. Here, we showed that lncRNA H19 expression was increased in the liver after ConA treatment, accompanied by increased exosome secretion. Moreover, injection of AAV‐H19 aggravated ConA‐induced hepatitis, with an increase in hepatocyte apoptosis. However, GW4869, an exosome inhibitor, alleviated ConA‐induced liver injury and inhibited the upregulation of lncRNA H19. Intriguingly, lncRNA H19 expression in the liver was significantly downregulated, after macrophage depletion. Importantly, the lncRNA H19 was primarily expressed in type I macrophage (M1) and encapsulated in M1‐derived exosomes. Furthermore, H19 was transported from M1 to hepatocytes via exosomes, and exosomal H19 dramatically induced hepatocytes apoptosis both in vitro and vivo. Mechanistically, H19 upregulated the transcription of hypoxia‐inducible factor‐1 alpha (HIF‐1α), which accumulated in the cytoplasm and mediated hepatocyte apoptosis by upregulating p53. M1‐derived exosomal lncRNA H19 plays a pivotal role in ConA‐induced hepatitis through the HIF‐1α–p53 signaling pathway. These findings identify M1 macrophage‐derived exosomal H19 as a novel target for the treatment of autoimmune liver diseases.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a significant impact on global health. To address the urgent need for plasmids containing SARS-CoV-2 sequences in research, we have developed a high-throughput FastCloning platform for the construction of associated plasmids. Our platform uses a FastCloning method to construct a plasmid library from 29 ORFs of the virus and 20 commonly used vectors in the lab. The library contains 536 recombinant vectors, with a highly positive clone success rate of 92.4%. Our study provides a rapid and efficient approach to constructing a large plasmid library for SARS-CoV-2 research.

BackgroundAlzheimer’s disease (AD) is the most common cause of dementia and cognitive decline, while its pathological mechanism remains unclear. Tauopathies is one of the most widely accepted hypotheses. In this study, the molecular network was established and the expression pattern of the core gene was analyzed, confirming that the dysfunction of protein folding and degradation is one of the critical factors for AD.MethodsThis study analyzed 9 normal people and 22 AD patients’ microarray data obtained from GSE1297 in Gene Expression Omnibus (GEO) database. The matrix decomposition analysis was used to identify the correlation between the molecular network and AD. The mathematics of the relationship between the Mini-Mental State Examination (MMSE) and the expression level of the genes involved in the molecular network was found by Neural Network (NN). Furthermore, the Support Vector Machine (SVM) model was for classification according to the expression value of genes.ResultsThe difference of eigenvalues is small in first three stages and increases dramatically in the severe stage. For example, the maximum eigenvalue changed to 0.79 in the severe group from 0.56 in the normal group. The sign of the elements in the eigenvectors of biggest eigenvalue reversed. The linear function of the relationship between clinical MMSE and gene expression values was observed. Then, the model of Neural Network (NN) is designed to predict the value of MMSE based on the linear function, and the predicted accuracy is up to 0.93. For the SVM classification, the accuracy of the model is 0.72.ConclusionThis study shows that the molecular network of protein folding and degradation represented by “BAG2-HSC70-STUB1-MAPT” has a strong relationship with the occurrence and progression of AD, and this degree of correlation of the four genes gradually weakens with the progression of AD. The mathematical mapping of the relationship between gene expression and clinical MMSE was found, and it can be used in predicting MMSE or classification with high accuracy. These genes are expected to be potential biomarkers for early diagnosis and treatment of AD.

Abstract Objective The purpose of this study was to examine the psychometric properties of the Attitude Survey Inclusive Education-Parents (ASIE-P) in mainland China. Methods A sample of 1,656 parents (70.59% female) from 27 provinces in mainland China completed the online survey. The data set was randomly split into two equal parts for exploratory factor analyses (EFA) and confirmatory factor analysis (CFA), respectively. Results The result of EFA showed two factors (emotion and cognition) underlining the Chinese parents’ attitude towards inclusive education. Results of CFA confirmed the two-factor structure and good psychometric properties of the Chinese version of the ASIE-P. Conclusions The two-factor structure of the Chinese version of the ASIE-P is different from that in Western societies. Despite this, the Chinese version of the ASIE-P is reliable and valid for Chinese parents, and can be used as a measurement tool for studies of Chinese parents' attitude toward inclusive education.

Abstract Infection with influenza A virus (IAV) can trigger pulmonary inflammation and lung damage. Osteopontin (OPN) is an essential regulator of cell death and immunity. However, the role and underlying mechanism of OPN in cell death in IAV-induced pulmonary injury remain poorly understood. Here, we demonstrated that OPN-deficient (OPN−/−) mice were insensitive to IAV, exhibiting decreased viral loads and attenuated lung injury after IAV infection compared to those in wild-type (WT) mice. Moreover, macrophage necroptosis was significantly reduced in OPN−/− mice infected with IAV compared to that in infected WT mice. OPN increased the expression of necroptosis-related genes and exacerbated macrophage necroptosis in IAV-infected THP1 cells. Notably, adoptive transfer of WT bone marrow-derived macrophages (BMDMs) or OPN−/− BMDMs into mice restored resistance to influenza infection, and the rescue effect of OPN−/− BMDMs was better than that of WT BMDMs. Collectively, these results suggest that OPN deficiency in macrophages reduces necroptosis, which leads to a decrease in viral titers and protects against IAV infection. Therefore, OPN is a potential target for the treatment of IAV infection.

Evaporation is a major component of both the surface energy balance and terrestrial water balance. Rapid urban development can change the climate of urban areas, which may have an impact on pan evaporation. In this study, we analyzed the differences in pan evaporation between urban and rural stations, using the Nanpan River Basin of China as the study area. Site pair analysis was conducted using evaporation and socioeconomic data from 25 meteorological and 14 hydrological stations from 1980 to 2016. An urbanization effects indicator, namely EUE, was created to quantify the urbanization effects. Subsequently, a gray relational analysis (GRA) between the urbanization effects indicator and socioeconomic indicators was conducted to identify the effect of socio-economic indicators on urbanization effects. The main results were as follows. (1) During the period 1980–2016, the pan evaporation in the Nanpan River Basin showed a decreasing trend, which was similar in both urban and rural stations, with slopes of −2.87 and −2.89 mm/yr, respectively. (2) After the sudden change in pan evaporation in the Nanpan River Basin in 2000, the slope difference between urban and rural stations increased significantly. The slope of pan evaporation at urban stations was −4.55 mm/yr, whereas that at rural stations was 1.01 mm/yr. The slope difference between urban and rural stations was −5.56 mm/yr, larger than that in 1980–2000 (−0.43 mm/yr). (3) Urbanization influenced the trend and slope of the long-term change in pan evaporation. The rising slope decreased after 2000 in two of the seven cities, and the rising trend changed to a decreasing one in five cities. The difference between the slopes in 2001–2016 and 1980–2000 △E was used as the urbanization effects indicator EUE, and the EUE of all seven cities was

Summary: Long noncoding RNAs (lncRNAs) participate in host antiviral responses; however, how viruses exploit host lncRNAs for immune evasion remains largely unexplored. Functional screening of differentially expressed lncRNA profile in patients infected with influenza A virus (IAV) revealed that lncNSPL (Gene Symbol: LOC105370355) was highly expressed in monocytes. Deregulated lncNSPL expression in infected monocytes significantly increased type I interferon (IFN-I) production and inhibited IAV replication. Moreover, lncNSPL overexpression in mice increased the susceptibility to IAV infection and impaired IFN-I production. LncNSPL directly bound to retinoic acid-inducible gene I (RIG-I) and blocked the interaction between RIG-I and E3 ligase tripartite interaction motif 25 (TRIM25), reducing TRIM25-mediated lysine 63 (K63)-linked RIG-I ubiquitination and limiting the downstream production of antiviral mediators during the late stage of IAV infection. Our findings provide mechanistic insights into the means by which lncNSPL promotes IAV replication and immune escape via restricting the TRIM25-mediated RIG-I K63-linked ubiquitination. Thus, lncNSPL may represent a promising pharmaceutical target for anti-IAV therapy.

Single nucleotide polymorphisms (SNPs) have been widely used for gene identification. Allelic discrimination for an individual SNP with high reliability and flexibility is critical for the accurate detection of beneficial genes linked to specific SNP sites. Several SNP genotyping platforms have been developed but most exclusively rely on fluorescence signals for allelic differentiation. Genotyping via a fluorescence signal can have a lower accuracy if strong background signal noise is present, a common challenge associated with crop genetics. The semi-thermal asymmetric reverse PCR (STARP) marker system introduces extra SNPs in its forward primers to ensure specificity of the PCR reaction and adds a 4-nucleotide insertion into one universal primer to create fragment length polymorphism among STARP markers, which makes SNP allelic discrimination possible through either fluorescence signals or traditional gel electrophoresis. The STARP marker system is preferable for SNP genotyping in crops such as sugarbeet (Beta vulgaris ssp. Vulgaris L.) that exhibit strong background signal noise during PCR reactions due to an abundant repetitive sequence and high levels of heterozygosity in the genome. In this study, SNPs among sugarbeet lines were detected through genotype-by-sequencing (GBS) and confirmed by sequencing PCR products containing SNP sites. STARP primers were designed, and they generated STARP markers clearly discriminated by SNP alleles among sugarbeet plants either through a fluorescence signal or fragment length polymorphism. In addition, by prolonging 5-nucleotide in an allele-specific forward primer F2 that increased fragment length polymorphism of STARP markers from 4-bp to 9-bp, genotyping individual SNPs can be performed using user-friendly agarose gels. This research resulted in the development of a STARP marker platform for the flexible genotyping of individual SNPs of sugarbeet as well as an improved STARP technique for easy SNP allelic discrimination that also has utilities in other plant species.

Quantification of the loss generation of ducted contra-rotating fan (CRF) blades is difficult to achieve, since there are no guide vanes between rotors. A blade design program was established to investigate the relationship between radial velocity distribution and incurred loss. Numerical and experimental techniques were used to confirm the optimal configuration’s overall performance. The relationship between loss and velocity distribution under the impact of spanwise load distribution was confirmed by the entropy contour from various perspectives. The appropriate radial velocity distribution can improve the operating efficiency of a CRF by reducing the entropy around the annulus under design and near-stall conditions. This regularity could provide some strategies in the design of contra-rotating blades.

Winter oilseed cash cover crops are gaining popularity in integrated weed management programs for suppressing weeds. A study was conducted at two field sites (Fargo, North Dakota, and Morris, Minnesota) to determine the freezing tolerance and weed-suppressing traits of winter canola/rapeseed (Brassica napus L.) and winter camelina [Camelina sativa (L.) Crantz] in the Upper Midwestern USA. The top 10 freezing tolerant accessions from a phenotyped population of winter canola/rapeseed were bulked and planted at both locations along with winter camelina (cv. Joelle) as a check. To phenotype our entire winter B. napus population (621 accessions) for freezing tolerance, seeds were also bulked and planted at both locations. All B. napus and camelina were no-till seeded at Fargo and Morris at two planting dates, late August (PD1) and mid-September (PD2) 2019. Data for winter survival of oilseed crops (plants m−2) and their corresponding weed suppression (plants m−2 and dry matter m−2) were collected on two sampling dates (SD) in May and June 2020. Crop and SD were significant (p < 0.05) for crop plant density at both locations, and PD in Fargo and crop x PD interaction in Morris were significant for weed dry matter. At Morris and Fargo, PD1 produced greater winter B. napus survival (28% and 5%, respectively) and PD2 produced higher camelina survival (79% and 72%, respectively). Based on coefficient of determination (r2), ~50% of weed density was explained by camelina density, whereas ≤20% was explained by B. napus density at both locations. Camelina from PD2 suppressed weed dry matter by >90% of fallow at both locations, whereas weed dry matter in B. napus was not significantly different from fallow at either PD. Genotyping of overwintering canola/rapeseed under field conditions identified nine accessions that survived at both locations, which also had excellent freezing tolerance under controlled conditions. These accessions are good candidates for improving freezing tolerance in commercial canola cultivars.

Crop wild relatives of the cultivated sunflower (Helianthus annuus L.) are a valuable resource for its sustainable production. Helianthus praecox ssp. runyonii is a wild sunflower known for its resistance against diseases caused by the fungus, Sclerotinia sclerotiorum (Lib.) de Bary, which infects over 400 broadleaf hosts including many important food crops. The objective of this research was to dissect the Sclerotinia basal stalk rot (BSR) resistance introgressed from H. praecox ssp. runyonii into cultivated sunflower. An advanced backcross quantitative trait loci (AB-QTL) mapping population was developed from the cross of a H. praecox accession with cultivated sunflower lines. The AB-QTL population was evaluated for BSR resistance in the field during the summers of 2017–2018 and in the greenhouse in the spring of 2018. Highly significant genetic variations (p

Abstract Winter biotypes of rapeseed (Brassica napus L.) require a vernalization treatment to enter the reproductive phase and generally produce greater yields than spring rapeseed. To find genetic loci associated with freezing tolerance in rapeseed, we first performed genotyping‐by‐sequencing (GBS) on a diversity panel consisting of 222 rapeseed accessions originating primarily from Europe, which identified 69,554 high‐quality single‐nucleotide polymorphisms (SNPs). Model‐based cluster analysis suggested that there were eight subgroups. The diversity panel was then phenotyped for freezing survival (visual damage and Fv/Fo and Fv/Fm) after 2 months of cold acclimation (5°C) and a freezing treatment (−15°C for 4 h). The genotypic and phenotypic data for each accession in the rapeseed diversity panel was then used to conduct a genome‐wide association study (GWAS). GWAS results showed that 14 significant markers were mapped to seven chromosomes for the phenotypes scored. Twenty‐four candidate genes located within the mapped loci were identified as previously associated with lipid, photosynthesis, flowering, ubiquitination, and cytochrome P450 in rapeseed or other plant species.

Nanpan River is the source of the Pearl River in China, and thus, the exploitation of water resources in the Nanpan River Basin directly affects development in its middle and lower reaches. In the present study, the availability of water resources in the Nanpan River Basin and their differences were investigated. Sixteen statistical variables including the 25th and 75th percentiles, the coefficient of variation of the seasonal and annual precipitation and the annual precipitation concentration index were examined using monthly precipitation data collected in 33 stations in the Nanpan River Basin from 1956 to 2016. This paper studies the relationship between the Spearman’s rank correlation coefficient and the distance between stations, and uses principal component analysis (PCA) and cluster analysis to identify the homogeneous precipitation regions in the Nanpan River Basin. The results reveal the following: 1) The Spearman’s rank correlation coefficients for the monthly, seasonal and annual precipitation of the stations exhibit negative correlations with the interstation distance; the stronger the spatial correlation between both parameters, the shorter the time scale. 2) The factors controlling the spatial patterns of precipitation in the basin are its interannual and intra-annual variations. 3) Precipitation for the Nanpan River Basin produce two homogenous regions, which are associated with the influences of the South Asian monsoon, the North Atlantic Oscillation and the South Branch Trough. The first region is mainly to the east of longitude 104°E, while the second is principally to the west.

To solve the problem of strong ground pressure behaviour under a residual coal pillar in the overlying goaf of a close-distance coal seam, this paper proposes the technology of weakening and relieving the residual coal pillar in the overlying goaf by a high-pressure water jet. Based on the geological occurrence of the No. 3 coal seam and mountain No. 4 coal seam in the Yanzishan coal mine, the high-pressure water jet pressure relief technology of residual coal pillars in the overlying goaf of close-distance coal seams was studied by theoretical analysis and field industrial tests. First, the elastic-plastic zone of the residual coal pillar and the stress distribution law of the floor are obtained by theoretical analysis, and the influence degree of the residual coal pillar on the support of the lower coal seam working face is revealed. Then, a high-pressure water jet combined with mine pressure is proposed to weaken the residual coal pillar. Finally, through the residual coal pillar hydraulic cutting mechanical model and “double-drilling double-slot” model, the high-pressure water jet drilling layout parameters are determined, and an industrial field test is carried out. The single knife cutting coal output and 38216 working face hydraulic support monitoring data show that high-pressure hydraulic slotting can weaken the strength of the coal body to a certain extent, destroy the integrity of the residual coal pillar, cut off the load transmission path of the overlying strata, and reduce the working resistance of the hydraulic support under the residual coal pillar to a certain extent, which is beneficial to the safe mining of the working face.

Fusarium head blight (FHB) is a devastating disease in wheat. The use of resistant germplasm from diverse sources can significantly improve resistance to the disease. “Surpresa” is a Brazilian spring wheat cultivar with moderate FHB resistance, different from currently used sources. In this study, we aimed to identify and map the genetic loci for FHB resistance in Surpresa. A mapping population consisting of 187 recombinant inbred lines (RILs) was developed from a cross between Surpresa and a susceptible spring wheat cultivar, “Wheaton.” The population was evaluated for FHB by the point-inoculation method in three greenhouse experiments and four field trials between 2016 and 2018. Mean disease severity for Surpresa and Wheaton was 41.2 and 84.9% across the 3 years of experiments, ranging from 30.3 to 59.1% and 74.3 to 91.4%, respectively. The mean FHB severity of the NILs was 57%, with an overall range from 7 to 100%, suggesting transgressive segregation in the population. The population was genotyped using a two-enzyme genotyping-by-sequencing approach, and a genetic map was constructed with 5,431 single nucleotide polymorphism (SNP) markers. Four QTL for type II resistance were detected on chromosomes 3A, 5A, 6A, and 7A, explaining 10.4–14.4% of the total phenotypic variation. The largest effect QTL was mapped on chromosome 7A and explained 14.4% of the phenotypic variation; however, it co-localized with a QTL governing the days to anthesis trait. A QTL for mycotoxin accumulation was also detected on chromosome 1B, explaining 18.8% of the total phenotypic variation. The QTL for FHB resistance identified in the study may diversify the FHB resistance gene pool and increase overall resistance to the disease in wheat.

The mine ventilator plays a role in protecting the life safety of underground workers, which is very significant to the production and development of coal mines. In total, 70% of ventilator failures are mechanical failures, and bearing failures are the most likely to occur in mechanical failures, which are also difficult to find. In order to identify fan bearing faults accurately, this paper proposes a fault diagnosis method based on improved variational mode decomposition and density peak clustering. First, the variational mode decomposition’s modal number K and secondary penalty factor α are chosen employing the improved sparrow optimization process. The bearing vibration signal is decomposed by the variational mode decomposition algorithm with optimized parameters. To create the characteristic vector, the multi-scale permutation entropy of the fourth order intrinsic mode function is determined. Then, the characteristic matrix is dimensionally reduced by kernel principal component analysis, and the two-dimensional matrix after dimensionality reduction is divided by density peak clustering method to find the clustering center of the training sample features. Lastly, the membership degree is assessed using the normalized clustering distance between the characteristic matrix of the test sample and the cluster center of the training sample. The accuracy of bearing fault identification on the self-constructed experimental platform can reach 100%, which verifies the effectiveness and potential of the proposed method.

Abstract Durumwheat [Triticum turgidum L. ssp. durum (Desf.)] production is constrained by fungal diseases including stripe rust caused by Puccinia striiformis Westend. f. sp. tritici Erikss. (Pst). Continuous mining of germplasm for the discovery and deployment of stripe rust resistance (Yr) genes is needed to counter the impact of this disease. In this study, we evaluated a worldwide collection of 432 durum wheat accessions to seven U.S. Pst races that carry diverse virulence and avirulence combinations on wheat Yr genes. We found that 47–82% of the durum wheat accessions were susceptible to each of the tested Pst races. A total of 32 accessions were resistant to all seven races. Genome‐wide association studies (GWAS) using over 97,000 single‐nucleotide polymorphism markers generated from genotyping‐by‐sequencing of 364 accessions identified 56 quantitative trait loci (QTL) associated with all‐stage stripe rust resistance located on all 14 durum wheat chromosomes. Six of these QTL were associated with resistance to 2–4 Pst races, and none were associated with resistance to all seven races. The remaining 50 QTL were race specific. Eighteen of the 56 identified QTL had relatively large effects against at least one of the races. A map‐based comparison of the discovered QTL in this study with previously published Yr genes and QTL showed that 29 were previously identified, whereas the remaining 27 QTL appeared to be novel. This study reports effective sources of stripe rust resistance to contemporary races in the United States and shows that this durum wheat collection is abundant in novel resistance loci that can be transferred into adapted durum cultivars.

A new dopant-free hole transporting material (HTM) 4′,4‴,4‴'',4‴''''-(adamantane-1,3,5,7-tetrayl)tetrakis(N,N-bis(4-methoxyphenyl)-[1,1′-biphenyl]-4-amine) (Ad-Ph-OMeTAD) (named FDY for short), which consists of a nonconjugated 3D bulky caged adamantane (Ad) as the core, triphenyl amines as side arms, and phenyl units as a linking bridge, is synthesized and applied in an inverted planar perovskite solar cell (PSC). As a result, the champion device with FDY as HTM yields an impressive power of conversion efficiency (PCE) of 18.69%, with JSC = 22.42 mA cm−2, VOC = 1.05 V, and FF = 79.31% under standard AM 1.5G illumination, which is ca. 20% higher than that of the device based on PEDOT:PSS (only 15.41%). Notably, the stability of PSC based on FDY is much better than that of devices based on PEDOT:PSS, and the corresponding devices retain over 90% of their initial PCEs after storing for 60 days in a nitrogen glove box without any encapsulation. Even when stored in an open air condition with 50–60% relative humidity for 188 h, the retained PCE is still over 81% of its initial one. All these results demonstrate that the new design strategy by combing the bulky and nonconjugated (aliphatic) adamantane unit as the core and triphenyl amines as side arms can efficiently develop highly efficient HTMs for PSCs, which is different from the traditional way based on conjugated backbones, and it may open a new way for scientists to design small-molecule HTMs for PSCs.

Lung cancer with loss-of-function of the LKB1 tumor suppressor is a common aggressive subgroup with no effective therapies. LKB1-deficiency induces constitutive activation of cAMP/CREB-mediated transcription by a family of three CREB-regulated transcription coactivators (CRTC1-3). However, the significance and mechanism of CRTC activation in promoting the aggressive phenotype of LKB1-null cancer remain poorly characterized. Here, we observed overlapping CRTC expression patterns and mild growth phenotypes of individual CRTC-knockouts in lung cancer, suggesting functional redundancy of CRTC1-3. We consequently designed a dominant-negative mutant (dnCRTC) to block all three CRTCs to bind and co-activate CREB. Expression of dnCRTC efficiently inhibited the aberrantly activated cAMP/CREB-mediated oncogenic transcriptional program induced by LKB1-deficiency, and specifically blocked the growth of human and murine LKB1-inactivated lung cancer. Collectively, this study provides direct proof for an essential role of the CRTC-CREB activation in promoting the malignant phenotypes of LKB1-null lung cancer and proposes the CRTC-CREB interaction interface as a novel therapeutic target.

The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacrolimus solid dispersion was prepared using glycerylbehenate (Compritol® ATO888) and Pluronic F127 as the carrier materials with hot-melt method, which was then blended with hydrogel matrix materials, such as HPMC and lactose, the powders were directly compressed into tablets. In vitro drug release tests were carried out to evaluate the performance of the solid dispersions and the tablets. The dissolution rate of tacrolimus was significantly improved by the lipid-based solid dispersion, and the incorporation of HPC into the solid dispersion obviously improved its stability after storage. Extended release tablets loaded with tacrolimus solid dispersion showed prolonged drug release patterns over 24 h, the release patterns of the tablets can be tailored by the compositions of the matrix materials, including the types and content of HPMCs. A modified processing method that directly mixed the melted solid dispersion with HPMC powders improved the uniformity of the solid dispersion inside the tablet matrix and release profile. The release data of the extended release tablet fitted well to the Korsmeyer–Peppas model with n value of 0.85, which suggested diffusion- and erosion-controlled release mechanism. The combination of lipid-based solid dispersion and HPMC hydrogel matrix may find wide applications in the extended release dosage forms of high potent, water-insoluble drugs. Keywords: Tacrolimus, Solid dispersion, Lipid, Extended-release tablet

Owing to the shortcomings of blindness and inaccuracy when backfilling in goafs and based on the key stratum theory, we propose the “multi-arch pier-column” backfilling method. This method involves drilling holes at specific locations on the surface to inject filling and slurry materials into the goaf and separation area under the key stratum. This allows the broken gangue to be cemented to form a stone body, to improve its overall strength. This process, along with filling in the separation area under the key stratum, ensures that the key stratum does not break, forming a joint medium of “separation area filling body + backfilled pier-columns + key stratum + coal column”, which prevents new subsidence on the surface layer. Using the Gaojialiang coal mine as an example, the effects of the proposed method on controlling surface subsidence were determined using a numerical simulation based on FLAC3D simulation software. The results indicate that this method can effectively control the key stratum and ensure that the surface subsidence is within a safe range. The multi-arch pier-column backfilling method utilises the self-bearing capacity of the overburden structure and greatly reduces the backfilling workload and the cost of backfilling for controlling surface subsidence. At present, the multi-arch pier-column system of the new backfill method is an unexplored and new area of research.

Basal stalk rot (BSR), caused by the fungus Sclerotinia sclerotiorum, is a serious disease of sunflower (Helianthus annuus L.) in the humid temperate growing areas of the world. BSR resistance is quantitative and conditioned by multiple genes. Our objective was to dissect the BSR resistance introduced from the wild annual species Helianthus argophyllus using a quantitative trait loci (QTL) mapping approach. An advanced backcross population (AB-QTL) with 134 lines derived from the cross of HA 89 with a H. argophyllus Torr. and Gray accession, PI 494573, was evaluated for BSR resistance in three field and one greenhouse growing seasons of 2017–2019. Highly significant genetic variations (p < 0.001) were observed for BSR disease incidence (DI) in all field screening tests and disease rating and area under the disease progress curve in the greenhouse. The AB-QTL population and its parental lines were genotyped using the genotyping-by-sequencing method. A genetic linkage map spanning 2,045.14 cM was constructed using 3,110 SNP markers mapped on 17 sunflower chromosomes. A total of 21 QTL associated with BSR resistance were detected on 11 chromosomes, each explaining a phenotypic variation ranging from 4.5 to 22.6%. Of the 21 QTL, eight were detected for BSR DI measured in the field, seven were detected for traits measured in the greenhouse, and six were detected from both field and greenhouse tests. Thirteen of the 21 QTL had favorable alleles from the H. argophyllus parent conferring increased BSR resistance.

Barley is an important cereal crop worldwide because of its use in the brewing and distilling industry. However, adequate supplies of quality malting barley are threatened by global climate change due to drought in some regions and excess precipitation in others, which facilitates epidemics caused by fungal pathogens. The disease net form net blotch caused by the necrotrophic fungal pathogen Pyrenophora teres f. teres (Ptt) has emerged as a global threat to barley production and diverse populations of Ptt have shown a capacity to overcome deployed genetic resistances. The barley line CI5791 exhibits remarkably effective resistance to diverse Ptt isolates from around the world that maps to two major QTL on chromosomes 3H and 6H. To identify genes involved in this effective resistance, CI5791 seed were γ-irradiated and two mutants, designated CI5791-γ3 and CI5791-γ8, with compromised Ptt resistance were identified from an M2 population. Phenotyping of CI5791-γ3 and -γ8 × Heartland F2 populations showed three resistant to one susceptible segregation ratios and CI5791-γ3 × -γ8 F1 individuals were susceptible, thus these independent mutants are in a single allelic gene. Thirty-four homozygous mutant (susceptible) CI5791-γ3 × Heartland F2 individuals, representing 68 recombinant gametes, were genotyped via PCR genotype by sequencing. The data were used for single marker regression mapping placing the mutation on chromosome 3H within an approximate 75 cM interval encompassing the 3H CI5791 resistance QTL. Sequencing of the mutants and wild-type (WT) CI5791 genomic DNA following exome capture identified independent mutations of the HvWRKY6 transcription factor located on chromosome 3H at ∼50.7 cM, within the genetically delimited region. Post transcriptional gene silencing of HvWRKY6 in barley line CI5791 resulted in Ptt susceptibility, confirming that it functions in NFNB resistance, validating it as the gene underlying the mutant phenotypes. Allele analysis and transcript regulation of HvWRKY6 from resistant and susceptible lines revealed sequence identity and upregulation upon pathogen challenge in all genotypes analyzed, suggesting a conserved transcription factor is involved in the defense against the necrotrophic pathogen. We hypothesize that HvWRKY6 functions as a conserved signaling component of defense mechanisms that restricts Ptt growth in barley.

The Nocardia rubra cell wall skeleton (Nr-CWS) for external use is an immune enhancer, which has been widely used in human cervix diseases such as cervical erosion, but the mechanism of Nr-CWS enhancing immunity is still unclear. The purpose of this study was to explore the effect and mechanism of Nr-CWS on the local immune status of cervical tissue in patients with high-risk human papillomavirus (HR-HPV) infection and cervical precancerous lesion, cervical intraepithelial neoplasia (CIN). The recruited patients with HR-HPV infection and CIN were treated with Nr-CWS. The specimens were taken from these patients before and after local application of Nr-CWS respectively. The normal control specimens were tested simultaneously. Serial section analysis of immunohistochemistry and co-expression analysis were performed to characterize populations of T cells and the expressions of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1). The levels of cytokines in local cervical tissue were also detected. Nr-CWS significantly increased T cells including CD4+, CD8+ T cells, and reduced the expression of PD-L1 in the patients’ local cervical tissues. Co-expression analyses showed that the proportions of PD-1+CD4+ cells in CD4+ T cells and PD-1+CD8+ cells in CD8+ T cells decreased after Nr-CWS application. Furthermore, the increase in the number of immune cells was accompanied by increased pro-inflammatory cytokines interleukin-12 (IL-12), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and decreased suppressive cytokine IL-10. The results indicate that Nr-CWS, as an immunotherapeutic agent for HR-HPV infection and CIN, plays an immune promoting role related to the upregulation of T cell subsets and the inhibition of PD-1/PD-L1 pathway.

Short carbon-fiber-reinforced composites, especially short carbon-fiber-reinforced polyetheretherketone composites (CF-PEEK), are used extensively in the engineering field because of their superior properties. However, their surface quality and material removal rate need to be optimized to satisfy design and processing requirements. This work focused on a multi-objective optimization to minimize the surface roughness and maximize the material removal rate during machining by grey relational analysis with an analysis-of-variance (ANOVA) and response surface methodology before a multi-objective mathematical model was established. The statistical significance of the predicted model was examined by using an ANOVA to obtain the optimal machining parameters (spindle speed, feed rate, cut depth). The optimal combination of cutting parameters was a spindle speed of 2600 rpm, a feed rate of 720 mm/min, and a cut depth of 1.8 mm.

Fusarium head blight (FHB) is one of the most destructive diseases in wheat worldwide. Breeding for FHB resistance is hampered by its complex genetic architecture, large genotype by environment interaction, and high cost of phenotype screening. Genomic selection (GS) is a powerful tool to enhance improvement of complex traits such as FHB resistance. The objectives of this study were to (1) investigate the genetic architecture of FHB resistance in a North Dakota State University (NDSU) hard red spring wheat breeding population, (2) test if the major QTL Fhb1 and Fhb5 play an important role in this breeding population; and (3) assess the potential of GS to enhance breeding efficiency of FHB resistance. A total of 439 elite spring wheat breeding lines from six breeding cycles were genotyped using genotyping-by-sequencing (GBS) and 102,147 SNP markers were obtained. Evaluation of FHB severity was conducted in 10 unbalanced field trials across multiple years and locations. One QTL for FHB resistance was identified and located on chromosome arm 1AL, explaining 5.3% of total phenotypic variation. The major type II resistance QTL Fhb1 only explained 3.1% of total phenotypic variation and the QTL Fhb5 was not significantly associated with FHB resistance in this breeding population. Our results suggest that integration of many genes with medium/minor effects in this breeding population should provide stable FHB resistance. Genomic prediction accuracies of 0.22–0.44 were obtained when predicting over breeding cycles in this study, indicating the potential of GS to enhance the improvement of FHB resistance.

Macrophages play a critical role in the pathogenesis of endotoxin shock by producing excessive amounts of pro-inflammatory cytokines. A pan-caspase inhibitor, zVAD, can be used to induce necroptosis under certain stimuli. The role of zVAD in both regulating the survival and activation of macrophages, and the pathogenesis of endotoxin shock remains not entirely clear. Here, we found that treatment of mice with zVAD could significantly reduce mortality and alleviate disease after lipopolysaccharide (LPS) challenge. Notably, in LPS-challenged mice, treatment with zVAD could also reduce the percentage of peritoneal macrophages by promoting necroptosis and inhibiting pro-inflammatory responses in macrophages. In vitro studies showed that pretreatment with zVAD promoted LPS-induced nitric oxide-mediated necroptosis of bone marrow-derived macrophages (BMDMs), leading to reduced pro-inflammatory cytokine secretion. Interestingly, zVAD treatment promoted the accumulation of myeloid-derived suppressor cells (MDSCs) in a mouse model of endotoxin shock, and this process inhibited LPS-induced pro-inflammatory responses in macrophages. Based on these findings, we conclude that treatment with zVAD alleviates LPS-induced endotoxic shock by inducing macrophage necroptosis and promoting MDSC-mediated inhibition of macrophage activation. Thus, this study provides insights into the effects of zVAD treatment in inflammatory diseases, especially endotoxic shock.

Depolymerization of lignin into valuable aromatic compounds is an important starting point for its valorization strategies, which requires the cleavage of C-O and C-C bonds between lignin monomer units. The catalytic cleavage of these bonds is still difficult and challenging. Our previous experimental investigation (Green Chem., 2018, 20: 3743) has shown that methyl p-hydroxycinnamate (MPC) can be produced from molecular tailoring of H unit in lignin by the cleavage of the γ-O ester bond. In this study, the mechanism of [Bmim][FeCl4]-catalyzed depolymerization of lignin was investigated by using the density functional theory (DFT) method. The results reveal that [FeCl4]− anion of the catalyst plays a decisive role in the whole catalytic process, where two possible activation modes including three different potential reaction pathways can realize the depolymerization of lignin model compound. The calculated overall barriers of the catalytic conversion along these potential routes show that the third potential pathway, i.e., methanol firstly activated by [Bmim][FeCl4], has the most probability with the lowest energy barrier, while the second pathway is excluded because the energy barrier is too high. Also, the results illustrate that the solvent effect is beneficial to the reduction of the relative energy for the reaction to form the transition states. Hence, the obtained molecular level information can identify the favorable conversion process catalyzed by metallic ionic liquids to a certain extent, and it is desirable to enhance the utilization of biomass as a ubiquitous feedstock.

Dysregulation of macrophage has been demonstrated to contribute to aberrant immune responses and inflammatory diseases. CD11b, expressed on macrophages, plays a critical role in regulating pathogen recognition, phagocytosis, and cell survival. In the present study, we explored the effect of leukadherin-1 (LA1), an agonist of CD11b, on regulating LPS-induced pro-inflammatory response in macrophages and endotoxic shock. Intriguingly, we found that LA1 could significantly reduce mortalities of mice and alleviated pathological injury of liver and lung in endotoxic shock. In vivo studies showed that LA1-induced activation of CD11b significantly inhibited the LPS-induced pro-inflammatory response in macrophages of mice. Moreover, LA1-induced activation of CD11b significantly inhibited LPS/IFN-γ-induced pro-inflammatory response in macrophages by inhibiting MAPKs and NF-κB signaling pathways in vitro. Furthermore, the mice injected with LA1-treated BMDMs showed fewer pathological lesions than those injected with vehicle-treated BMDMs in endotoxic shock. In addition, we found that activation of TLR4 by LPS could endocytose CD11b and activation of CD11b by LA1 could endocytose TLR4 in vitro and in vivo, subsequently blocking the binding of LPS with TLR4. Based on these findings, we concluded that LA1-induced activation of CD11b negatively regulates LPS-induced pro-inflammatory response in macrophages and subsequently protects mice from endotoxin shock by partially blocking LPS-TLR4 interaction. Our study provides a new insight into the role of CD11b in the pathogenesis of inflammatory diseases.

The histone demethylase LSD1 facilitates epithelial-to-mesenchymal transition (EMT) and tumor progression by repressing epithelial marker expression. However, little is known about how its function may be modulated. Here, we report that LSD1 is acetylated in epithelial but not mesenchymal cells. Acetylation of LSD1 reduces its association with nucleosomes, thus increasing histone H3K4 methylation at its target genes and activating transcription. The MOF acetyltransferase interacts with LSD1 and is responsible for its acetylation. MOF is preferentially expressed in epithelial cells and is downregulated by EMT-inducing signals. Expression of exogenous MOF impedes LSD1 binding to epithelial gene promoters and histone demethylation, thereby suppressing EMT and tumor invasion. Conversely, MOF depletion enhances EMT and tumor metastasis. In human cancer, high MOF expression correlates with epithelial markers and a favorable prognosis. These findings provide insight into the regulation of LSD1 and EMT and identify MOF as a critical suppressor of EMT and tumor progression.