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Background: The primary cause of cancer‐related fatalities globally is lung cancer. Although the chemotherapy drug cisplatin (DDP) has brought certain benefits to patients, the rapid development of drug resistance has greatly hindered treatment success. Methods: We used the lung squamous cell carcinoma (LUSC) mRNA data set to explore the differentially expressed gene (RND1) in LUSC and detected RND1 expression in LUSC cells and DDP‐resistant cells by qRT‐PCR. Meanwhile, we performed abnormal expression treatment on RND1 and conducted CCK8, colony formation, and flow cytometry to evaluate the impact of RND1 expression on cell proliferation, apoptosis, and DDP resistance. In addition, we analyzed metabolism pathways involving RND1 using GSEA. We also used online tools such as hTFtarget and JASPAR to screen for the upstream transcription factor FOXA2 of RND1 and verified their relationship through CHIP and dual luciferase experiments. Finally, we validated the role of FOXA2‐RND1 in DDP resistance in LUSC through the above experiments. Results: RND1 was downregulated in LUSC, and overexpression of RND1 repressed proliferation and DDP resistance of LUSC cells and facilitated cell apoptosis. RND1 modulated the arachidonic acid (AA) metabolism pathway, and FOXA2 positively manipulated RND1 expression. By activating FOXA2, stabilizing RND1, and regulating AA levels, the sensitivity of LUSC cells to DDP could be enhanced. Conclusion: Our study suggested that FOXA2 positively modulated the RND1‐AA pathway, which repressed the resistance of LUSC cells to DDP. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is considered as a disease of placental origin. However, the specific mechanism of placental abnormalities remains elusive. This study identified thrombospondin‐1 (THBS1) is downregulated in preeclamptic placentae and negatively correlated with blood pressure. Functional studies show that THBS1 knockdown inhibits proliferation, migration, and invasion and increases the cycle arrest and apoptosis rate of HTR8/SVneo cells. Importantly, THBS1 silencing induces necroptosis in HTR8/SVneo cells, accompanied by the release of damage‐associated molecular patterns (DAMPs). Necroptosis inhibitors necrostatin‐1 and GSK′872 restore the trophoblast survival while pan‐caspase inhibitor Z‐VAD‐FMK has no effect. Mechanistically, the results show that THBS1 interacts with transforming growth factor B‐activated kinase 1 (TAK1), which is a central modulator of necroptosis quiescence and affects its stability. Moreover, THBS1 silencing up‐regulates the expression of neuronal precursor cell‐expressed developmentally down‐regulated 4 (NEDD4), which acts as an E3 ligase of TAK1 and catalyzes K48‐linked ubiquitination of TAK1 in HTR8/SVneo cells. Besides, THBS1 attenuates PE phenotypes and improves the placental necroptosis in vivo. Taken together, the down‐regulation of THBS1 destabilizes TAK1 by activating NEDD4‐mediated, K48‐linked TAK1 ubiquitination and promotes necroptosis and DAMPs release in trophoblast cells, thus participating in the pathogenesis of PE. [ABSTRACT FROM AUTHOR]

Spirobisnaphthalenes (SBNs) are a class of highly oxygenated, fungal bisnaphthalenes containing a unique spiroketal bridge, that displayed diverse bioactivities. Among the reported SBNs, palmarumycins are the major type, which are precursors for the other type of SBNs structurally. However, the biosynthesis of SBNs is unclear. In this study, we elucidated the biosynthesis of palmarumycins, using gene disruption, heterologous expression, and substrate feeding experiments. The biosynthetic gene cluster for palmarumycins was identified to be distant from the polyketide synthase gene cluster, and included two cytochrome P450s (PalA and PalB), and one short chain dehydrogenase/reductase (PalC) encoding genes as key structural genes. PalA is an unusual, multifunctional P450 that catalyzes the oxidative dimerization of 1,8‐dihydroxynaphthalene to generate the spiroketal linkage and 2,3‐epoxy group. Chemical synthesis of key intermediate and in vitro biochemical assays proved that the oxidative dimerization proceeded via a binaphthyl ether. PalB installs the C‐5 hydroxy group, widely found in SBNs. PalC catalyzes 1‐keto reduction, the reverse 1‐dehydrogenation, and 2,3‐epoxide reduction. Moreover, an FAD‐dependent oxidoreductase, encoded by palD, which locates outside the cluster, functions as a 1‐dehydrogenase. These results provided the first genetic and biochemical evidence for the biosynthesis of palmarumycin SBNs. [ABSTRACT FROM AUTHOR]

The incidence of colibacillosis in poultry is on the rise, significantly affecting the chicken industry. Ceftiofur sodium (CS) is frequently employed to treat this disease, resulting in lipopolysaccharide (LPS) buildup. Processing plays a vital role in traditional Chinese veterinary medicine. The potential intervention in liver injury by polysaccharides from the differently processed products of Angelica sinensis (PDPPAS) induced by combined CS and LPS remains unclear. This study aims to investigate the protective effect of PDPPAS on chicken liver injury caused by CS combined with LPS buildup and further identify the polysaccharides with the highest hepatoprotective activity in chickens. Furthermore, the study elucidates polysaccharides' intervention mechanism using tandem mass tag (TMT) proteomics and multiple reaction monitoring (MRM) methods. A total of 190 1‐day‐old layer chickens were randomly assigned into 12 groups, of which 14 chickens were in the control group and 16 in other groups, for a 10‐day trial. The screening results showed that charred A. sinensis polysaccharide (CASP) had the most effective and the best hepatoprotective effect at 48 h. TMT proteomics and MRM validation results demonstrated that the intervention mechanism of the CASP high‐dose (CASPH) intervention group was closely related to the protein expressions of FCER2, TBXAS1, CD34, AGXT, GCAT, COX7A2L, and CYP2AC1. Conclusively, the intervention mechanism of CASPH had multitarget, multicenter regulatory features. [ABSTRACT FROM AUTHOR]

Tracking error leads to nonuniform flux distribution, local high temperature, and thermal stress of cavity receiver. However, the effects of tracking error on the optical–thermal conversion of dish concentrator–cavity receiver (DCCR) system are unclear. In this article, the optical–thermal coupling model of the DCCR system considering the tracking error is established, and the variations of the thermal performance index (the thermal efficiency, cavity maximum temperature, and outlet temperature) of the DCCR system under different direct normal irradiance (DNI), mass flow rate, inlet temperature, and cavity material are studied in detail. In the results, it is shown that the working condition is constant, tracking error increases, the outlet temperature and thermal efficiency decrease slightly, and the cavity maximum temperature increases. When tracking error is constant, with the increase of DNI or inlet temperature, the outlet and cavity maximum temperature increase, and the thermal efficiency decreases. With the increase of mass flow rate, the outlet and cavity maximum temperature decrease, and thermal efficiency increases. The cavity material with high thermal conductivity is beneficial to reduce the cavity maximum temperature. In this work, guidance for realizing safe and efficient service support can be provided. [ABSTRACT FROM AUTHOR]

Objective: Pediatric inferior turbinate hypertrophy (PedTH) is a frequent and often overlooked cause or associated cause of nasal breathing difficulties. This clinical consensus statement (CCS) aims to provide a diagnosis and management framework covering the lack of specific guidelines for this condition and addressing the existing controversies. Methods: A clinical consensus statement (CCS) was developed by a panel of 20 contributors from 7 different European and North American countries using the modified Delphi method. The aim of the CCS was to offer a multidisciplinary reference framework for the management of PedTH on the basis of shared clinical experience and analysis of the strongest evidence currently available. Results: A systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) criteria was performed. From the initial 96 items identified, 7 articles were selected based on higher‐evidence items such as randomized‐controlled trials, guidelines, and systematic reviews. A 34‐statement survey was developed, and after three rounds of voting, 2 items reached strong consensus, 17 reached consensus or near consensus, and 15 had no consensus. Conclusions: Until further prospective data are available, our CCS should provide a useful reference for PedTH management. PedTH should be considered a nasal obstructive disease not necessarily related to an adult condition but frequently associated with other nasal or craniofacial disorders. Diagnosis requires clinical examination and endoscopy, whereas rhinomanometry, nasal cytology, and questionnaires have little clinical role. Treatment choice should consider the specific indications and features of the available options, with a preference for less invasive procedures. Level of Evidence: 5 Laryngoscope, 134:1437–1444, 2024 [ABSTRACT FROM AUTHOR]

Summary: Brassinosteroids (BRs) play a crucial role in shaping the architecture of rice (Oryza sativa) plants. However, the regulatory mechanism of BR signalling in rice immunity remains largely unexplored. Here we identify a rice mutant dla, which exhibits decreased leaf angles and is insensitive to 24‐epiBL (a highly active synthetic BR), resembling the BR‐deficient phenotype. The dla mutation caused by a T‐DNA insertion in the OsDLA gene leads to downregulation of the causative gene. The OsDLA knockout plants display reduced leaf angles and less sensitivity to 24‐epiBL. In addition, both dla mutant and OsDLA knockout plants are more susceptible to rice blast compared to the wild type. OsDLA is a GRAS transcription factor and interacts with the BR signalling core negative regulator, GSK2. GSK2 phosphorylates OsDLA for degradation via the 26S proteasome. The GSK2 RNAi line exhibits enhanced rice blast resistance, while the overexpression lines thereof show susceptibility to rice blast. Furthermore, we show that OsDLA interacts with and stabilizes the WRKY transcription factor OsWRKY53, which has been demonstrated to positively regulate BR signalling and blast resistance. OsWRKY53 directly binds the promoter of PBZ1 and activates its expression, and this activation can be enhanced by OsDLA. Together, our findings unravel a novel mechanism whereby the GSK2‐OsDLA‐OsWRKY53 module coordinates blast resistance and plant architecture via BR signalling in rice. [ABSTRACT FROM AUTHOR]

2D metallic transition‐metal dichalcogenides (MTMDCs) have attracted widespread research interest in the exploration of fundamental physical issues and energy‐related fields. Although relatively high catalytic activity has been predicted theoretically in the new type MTMDCs‐based electrocatalysts, their hydrogen evolution reaction (HER) performance is severely hampered by the insufficient catalytic stability due to structural degradation during long‐time use and limited active sites in planar electrode structures. Herein, the scalable synthesis of vertically‐oriented 2H‐NbS2 nanosheets is reported on low‐cost carbon nanotube (CNT) film substrates by a facile chemical vapor deposition route. The 3D vertically‐oriented 2H‐NbS2 nanosheets present abundant edge active sites and strong interface coupling with CNT thus possessing exceptional mechanical stability. These features impart the 3D nanosheets catalysts with remarkably low overpotentials of ≈55 mV at 10 mA cm−2 and ultra‐high exchange current density of ≈1445 µA cm−2, and negligible performance degradation after 200 h operation at the large current density, which are superior to those of other TMDCs‐based catalysts. This work hereby provides novel perspectives for the batch synthesis and application of 3D MTMDCs‐based electrocatalysts with greatly improved electrocatalytic performance and stability that are needed for practical applications. [ABSTRACT FROM AUTHOR]

Summary: In eukaryotes, the majority of newly synthesized integral membrane proteins are inserted into the endoplasmic reticulum (ER) membrane before transferred to their functional sites. The conserved ER membrane complex (EMC) takes part in the insertion process for tail‐anchored membrane proteins. However, the function of EMC in phytopathogenic fungi has not been characterized.Here, we report the identification and functional characterization of two EMC subunits MoEmc5 and MoEmc2 in Magnaporthe oryzae. The knockout mutants ΔMoemc5 and ΔMoemc2 exhibit substantial defect in autophagy, pathogenicity, cell wall integrity, and magnesium ion sensitivity.We demonstrate that the autophagy process was severely impaired in the ΔMoemc5 and ΔMoemc2 mutants because of the low‐protein steady‐state level of Atg9, the sole membrane‐associated autophagy protein. Furthermore, the protein level of membrane proteins Chs4, Fks1, and MoMnr2 is also significantly reduced in the ΔMoemc5 and ΔMoemc2 strains, leading to their supersensitivity to Calcofluor white, Congo red, and magnesium. In addition, MoEmc5, but not MoEmc2, acts as a magnesium transporter independent of its EMC function.Magnaporthe oryzae EMC regulates the biogenesis of membrane proteins for autophagy and virulence; therefore, EMC subunits could be potential targets for fungicide design in the future. [ABSTRACT FROM AUTHOR]

Summary: Rice false smut caused by Ustilaginoidea virens is becoming one of the most recalcitrant rice diseases worldwide. However, the molecular mechanisms underlying rice immunity against U. virens remain unknown.Using genetic, biochemical and disease resistance assays, we demonstrated that the xb24 knockout lines generated in non‐Xa21 rice background exhibit an enhanced susceptibility to the fungal pathogens U. virens and Magnaporthe oryzae. Consistently, flg22‐ and chitin‐induced oxidative burst and expression of pathogenesis‐related genes in the xb24 knockout lines were greatly attenuated.As a central mediator of energy signaling, SnRK1A interacts with and phosphorylates XB24 at Thr83 residue to promote ATPase activity. SnRK1A is activated by pathogen‐associated molecular patterns and positively regulates plant immune responses and disease resistance. Furthermore, the virulence effector SCRE1 in U. virens targets host ATPase XB24. The interaction inhibits ATPase activity of XB24 by blocking ATP binding to XB24. Meanwhile, SCRE1 outcompetes SnRK1A for XB24 binding, and thereby suppresses SnRK1A‐mediated phosphorylation and ATPase activity of XB24.Our results indicate that the conserved SnRK1A‐XB24 module in multiple crop plants positively contributes to plant immunity and uncover an unidentified molecular strategy to promote infection in U. virens and a novel host target in fungal pathogenesis. [ABSTRACT FROM AUTHOR]

As an industry leader in digitalization and implementation of value‐added data‐driven methodologies, Dow is executing a structured evaluation of predictive maintenance (PdM) vendor offerings. PdM offers a tailored alternative to scheduled maintenance or run‐to‐failure operations, but the identification of suitable solutions offered by third parties is not trivial given the large number of offerings. This paper describes a methodology developed by Dow to deal with the challenge of efficiently screening many vendors with relevant PdM offerings. Prior to the evaluation process, scoring criteria for vendor performance must be identified. For Dow, these included the requirements (1) models can be created and deployed easily, (2) modeled asset health provides information for root causes, (3) the software operates in our preferred IT architecture, (4) confidential data cannot leave the premises, and (5) models have some transparency. The process involves four steps beginning with vendor identification, which explored existing relationships and landscape surveys. Following was the completion of a questionnaire by vendors about the offering. Upon positive completion, a dataset for two reflux pumps was provided for a first demonstration of the tool. The model performance was compared to internal modeling efforts, of which key results are shared in this paper. The last step involved an in‐depth evaluation including on‐site installation and online deployment of the PdM models, allowing scoring of all categories. What is presented herein is a framework that can be utilized for screening predictive maintenance modeling tools as well as many analytics applications arising in the age of Industry 4.0. [ABSTRACT FROM AUTHOR]

Summary: Necrosis‐ and ethylene‐inducing peptide 1 (Nep1)‐like proteins (NLPs) constitute a superfamily of proteins toxic to dicot plants, but the molecular basis of this toxicity remains obscure.Using quantitative trait locus (QTL) analysis we investigated the genetic variation underlying ion leakage in Arabidopsis plants elicited with MoNLP1 derived from Magnaporthe oryzae. The QTL conditioning MoNLP1 toxicity was positionally cloned and further characterized to elucidate its mode of action.MoNLP1‐triggered cell death varied significantly across > 250 Arabidopsis accessions and three QTLs were identified conferring the observed variation. The QTL on chromosome 4 was uncovered to encode a leucine‐rich repeat (LRR)‐only protein designated as NTCD4, which shares high sequence identity with a set of nucleotide‐binding LRR proteins. NTCD4 was secreted into the apoplast and physically interacted with multiple NLPs. Apoplastic NTCD4 facilitated the oligomerization of NLP, which was closely associated with toxicity in planta. The natural genetic variation causing D3N change in NTCD4 reduced the secretion efficiency of NTCD4 and the infection of Botrytis cinerea on Arabidopsis plants.These observations demonstrate that the plant‐derived NTCD4 is recruited by NLPs to promote toxicity via facilitating their oligomerization, which extends our understanding of a key step in the toxic mode of action of NLPs. [ABSTRACT FROM AUTHOR]

Objective: This study summarizes the anatomical features of the superior laryngeal nerve in Chinese to enable the rapid location of the superior laryngeal nerve during an operation. Study Design: Retrospective analysis of anatomical data. Setting: Hangzhou First People's Hospital Affiliated to Nanjing Medical University. Methods: A total of 71 embalmed human cadavers (132 heminecks) were examined over 3 months. The length and diameter of the internal and external branches of the superior laryngeal nerve and their relationships with different landmarks were recorded. Results: The total length of the internal branch of the superior laryngeal nerve was 23.4 ± 6.9 mm. The length of the external branch of the superior laryngeal nerve was 47.7 ± 11.0 mm. Considering the midpoint of the lower edge of the thyroid cartilage as the starting point and using that edge as a horizontal line, when the entry point is above that line, the external branch of the superior laryngeal nerve can be found within 41.1 mm and at an angle of 57.2°. When the entry point is below the lower edge of the thyroid cartilage, the external branch of the superior laryngeal nerve can be found within 34.0 mm and at an angle of 36.5°. Conclusion: The superior laryngeal nerve in Chinese people has distinct anatomical characteristics. This article provides a new method of quickly locating the external branch of the superior laryngeal nerve during the operation, which can reduce the probability of damaging the external branch of the superior laryngeal nerve. [ABSTRACT FROM AUTHOR]

Summary: Lesion mimic mutants are used to elucidate mechanisms controlling plant responses to pathogen attacks and environmental stresses. Although dozens of genes had been functionally demonstrated to be involved in lesion mimic phenotype in several plant species, the molecular mechanisms underlying the hypersensitive response are largely unknown. Here, a rice (Oryza sativa) lesion mimic mutant natural blight leaf 3 (nbl3) was identified from T‐DNA insertion lines. The causative gene, OsNBL3, encodes a mitochondrion‐localized pentatricopeptide repeat (PPR) protein. The nbl3 mutant exhibited spontaneous cell death response and H2O2 accumulation, and displayed enhanced resistance to the fungal and bacterial pathogens Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae. This resistance was consistent with the up‐regulation of several defence‐related genes; thus, defence responses were induced in nbl3. RNA interference lines of OsNBL3 exhibited enhanced disease resistance similar to that of nbl3, while the disease resistance in overexpression lines did not differ from that of the wild type. In addition, nbl3 displayed improved tolerance to salt, accompanied by up‐regulation of several salt‐associated marker genes. OsNBL3 was found to mainly participate in the splicing of mitochondrial gene nad5 intron 4. Disruption of OsNBL3 leads to the reduction in complex I activity, the elevation of alternative respiratory pathways and the destruction of mitochondrial morphology. Overall, the results demonstrated that the PPR protein‐coding gene OsNBL3 is essential for mitochondrial development and functions, and its disruption causes the lesion mimic phenotype and enhances disease resistance and tolerance to salt in rice. [ABSTRACT FROM AUTHOR]

Summary: The splicing factor Cwf15 is an essential component of the Prp19‐associated component of the spliceosome and regulates intron splicing in several model species, including yeasts and human cells. However, the roles of Cwf15 remain unexplored in plant pathogenic fungi. Here, we report that MoCWF15 in the rice blast fungus Magnaporthe oryzae is non‐essential to viability and important to fungal virulence, growth and conidiation. MoCwf15 contains a putative nuclear localization signal (NLS) and is localized into the nucleus. The NLS sequence but not the predicted phosphorylation site or two sumoylation sites was essential for the biological functions of MoCwf15. Importantly, MoCwf15 physically interacted with the Prp19‐associated splicing factors MoCwf4, MoSsa1 and MoCyp1, and negatively regulated protein accumulations of MoCyp1 and MoCwf4. Furthermore, with the deletion of MoCWF15, aberrant intron splicing occurred in near 400 genes, 20 of which were important to the fungal development and virulence. Taken together, MoCWF15 regulates fungal growth and infection‐related development by modulating the intron splicing efficiency of a subset of genes in the rice blast fungus. [ABSTRACT FROM AUTHOR]

Summary: Glycosylphosphatidylinositol (GPI) anchoring plays key roles in many biological processes by targeting proteins to the cell wall; however, its roles are largely unknown in plant pathogenic fungi. Here, we reveal the roles of the GPI anchoring in Magnaporthe oryzae during plant infection. The GPI‐anchored proteins were found to highly accumulate in appressoria and invasive hyphae. Disruption of GPI7, a GPI anchor‐pathway gene, led to a significant reduction in virulence. The Δgpi7 mutant showed significant defects in penetration and invasive growth. This mutant also displayed defects of the cell wall architecture, suggesting GPI7 is required for cell wall biogenesis. Removal of GPI‐anchored proteins in the wild‐type strain by hydrofluoric acid (HF) pyridine treatment exposed both the chitin and β‐1,3‐glucans to the host immune system. Exposure of the chitin and β‐1,3‐glucans was also observed in the Δgpi7 mutant, indicating GPI‐anchored proteins are required for immune evasion. The GPI anchoring can regulate subcellular localization of the Gel proteins in the cell wall for appressorial penetration and abundance of which for invasive growth. Our results indicate the GPI anchoring facilitates the penetration of M. oryzae into host cells by affecting the cell wall integrity and the evasion of host immune recognition. [ABSTRACT FROM AUTHOR]

An effective and robust hybrid algorithm consisting of particle swarm optimisation (PSO) and limited memory Broyden–Fletcher–Goldfarb–Shanno (L‐BFGS) method based on artificial neural network (ANN) is proposed for modelling flexible metal‐oxide thin‐film transistors (TFTs). The L‐BFGS method as an optimiser is exploited to update the parameters of ANN and speed up the training process. A mutation strategy for PSO is derived to enhance the searching ability further. With the great global searching ability, PSO is implemented to find a hopeful initial position in solution space for the next ANN model. The simulation result shows a high accuracy not only in I–V curve fitting but also in small‐signal parameter (gm, gd, etc.) predictions, which have not been exposed in the training process. The measured DC characteristics of In–Zn–O TFTs are used to verify the proposed ANN model, which has the benefits of rapid fitting from the L‐BFGS algorithm and universal searching ability from PSO. [ABSTRACT FROM AUTHOR]

Summary: The biotrophic fungal pathogen Ustilaginoidea virens causes rice false smut, a newly emerging plant disease that has become epidemic worldwide in recent years. The U. virens genome encodes many putative effector proteins that, based on the study of other pathosystems, could play an essential role in fungal virulence. However, few studies have been reported on virulence functions of individual U. virens effectors. Here, we report our identification and characterization of the secreted cysteine‐rich protein SCRE1, which is an essential virulence effector in U. virens. When SCRE1 was heterologously expressed in Magnaporthe oryzae, the protein was secreted and translocated into plant cells during infection. SCRE1 suppresses the immunity‐associated hypersensitive response in the nonhost plant Nicotiana benthamiana. Induced expression of SCRE1 in rice also inhibits pattern‐triggered immunity and enhances disease susceptibility to rice bacterial and fungal pathogens. The immunosuppressive activity is localized to a small peptide region that contains an important 'cysteine‐proline‐alanine‐arginine‐serine' motif. Furthermore, the scre1 knockout mutant generated using the CRISPR/Cas9 system is attenuated in U. virens virulence to rice, which is greatly complemented by the full‐length SCRE1 gene. Collectively, this study indicates that the effector SCRE1 is able to inhibit host immunity and is required for full virulence of U. virens. [ABSTRACT FROM AUTHOR]

Histone demethylase KDM7A regulates neuronal differentiation and development in mammals. In this study, we found that KDM7A was also required for breast cancer stem cells (BCSCs) maintenance. Silencing KDM7A significantly reduced the BCSCs population and mamosphere formation in vitro, and inhibited breast tumor growth in vivo. Restoring KDM7A expression rescued the defect in stem cell maintenance. Our mechanism analysis suggested that KDM7A upregulated the stemness‐associated factors KLF4 and c‐MYC for BCSCs maintenance. In addition, KDM7A knockdown promoted apoptosis through decreasing BCL2 expression and BAD phosphorylation in breast cancer (BrCa). Furthermore, restoring KDM7A and BCL2 expression rescued apoptosis inhibition in breast cancer, suggesting that KDM7A inhibited apoptosis by upregulating the BCL2 level in breast cancer. In conclusion, KDM7A promotes cancer stem cell maintenance and apoptosis inhibition in breast cancer. [ABSTRACT FROM AUTHOR]

Despite the improvement in acute myeloid leukemia (AML) treatments, most patients had a poor prognosis and suffered from chemoresistance and disease relapse. Therefore, there is an urgent need for elucidation of mechanism(s) underlying drug resistance in AML. In the present study, we found that AML cells showed less susceptibility to adriamycin (ADR) in the presence of hypoxia, while inhibition of hypoxia‐inducible factor 1α (HIF‐1α) by CdCl2 can make AML cells re‐susceptibile to ADR even under hypoxia. Moreover, HIF‐1α is overexpressed and plays an important role in ADR‐resistance maintenance in resistant AML cells. We further found hypoxia or induction of HIF‐1α can significantly upregulate yes‐associated protein (YAP) expression in AML cells, and resistant cells express a high level of YAP. Finally, we found that YAP may not only enhance HIF‐1α stability but also promote HIF‐1α's activity on the target gene pyruvate kinase M2. In conclusion, our data indicate that HIF‐1α or YAP may represent a therapeutic target for overcoming resistance toward adriamycin‐based chemotherapy in AML. [ABSTRACT FROM AUTHOR]

Summary: Bacteriocins are regarded as important factors mediating microbial interactions, but their exact role in community ecology largely remains to be elucidated. Here, we report the characterization of a mutant strain, derived from Pseudomonas syringae pv. tomato DC3000 (Pst), that was incapable of growing in plant extracts and causing disease. Results showed that deficiency in a previously unannotated gene saxE led to the sensitivity of the mutant to Ca2+ in leaf extracts. Transposon insertions in the bacteriocin gene syrM, adjacent to saxE, fully rescued the bacterial virulence and growth of the ΔsaxE mutant in plant extracts, indicating that syrM‐saxE encode a pair of bacteriocin immunity proteins in Pst. To investigate whether the syrM‐saxE system conferred any advantage to Pst in competition with other SyrM‐sensitive pathovars, we compared the growth of a SyrM‐sensitive strain co‐inoculated with Pst strains with or without the syrM gene and observed a significant syrM‐dependent growth reduction of the sensitive bacteria on plate and in lesion tissues upon desiccation–rehydration treatment. These findings reveal an important biological role of SyrM‐like bacteriocins and help to understand the complex strategies used by P. syringae in adaptation to the phyllosphere niche in the context of plant disease. [ABSTRACT FROM AUTHOR]

Summary: Fungal avirulence effectors, a key weapon utilized by pathogens to promote their infection, are recognized by immune receptors to boost host R gene‐mediated resistance. Many avirulence effectors share sparse sequence homology to proteins with known functions, and their molecular and biochemical functions together with the evolutionary relationship among different members remain largely unknown. Here, the crystal structure of AvrPib, an avirulence effector from Magnaporthe oryzae, was determined and showed a high degree of similarity to the M. oryzae Avrs and To xB (MAX) effectors. Compared with other MAX effectors, AvrPib has a distinct positive‐charge patch formed by five positive‐charged residues (K29, K30, R50, K52 and K70) on the surface. These five key residues were essential to avirulence function of AvrPib and affected its nuclear localization into host cells. Moreover, residues V39 and V58, which locate in the hydrophobic core of the structure, cause loss of function of AvrPib by single‐point mutation in natural isolates. In comparison with the wild‐type AvrPib, the V39A or V58A mutations resulted in a partial or entire loss of secondary structure elements. Taken together, our results suggest that differences in the surface charge distribution of avirulence proteins could be one of the major bases for the variation in effector–receptor specificity, and that destabilization of the hydrophobic core is one of the major mechanisms employed by AvrPib for the fungus to evade recognition by resistance factors in the host cell. [ABSTRACT FROM AUTHOR]

Summary: Protein post‐translational modifications play critical roles in cellular processes, development and stress response. The small ubiquitin‐like modifier (SUMO) to proteins is one of the essential modifications in eukaryotes, but its function remains largely unknown in plant pathogenic fungi. We present a comprehensive analysis combined with proteomic, molecular and cellular approaches to explore the roles of sumoylation in the model plant fungal pathogen, Magnaporthe oryzae. We found the SUMO pathway plays key roles in colony growth, conidia formation and virulence to the host, as well as cell‐cycle‐related phenotypes. Sumoylation is also involved in responding to different stresses. Affinity purification identified 940 putative SUMO substrates, many of which were reported to be involved in development, stress response and infection. Interestingly, four septins were also shown to be sumoylated. Mutation of consensus sumoylation sites in each septin all resulted in reduced virulence to the host and dislocation of septins in appressoria. Moreover, sumoylation is also involved in extracellular secretion of different effector proteins. Our study on the functions of sumoylation provides novel insight into development and infection of the rice blast fungus. [ABSTRACT FROM AUTHOR]

Summary: Glutamate homeostasis plays a vital role in central nitrogen metabolism and coordinates several key metabolic functions. However, its function in fungal pathogenesis and development has not been investigated in detail. In this study, we identified and characterized a glutamate synthase gene MoGLT1 in the rice blast fungus Magnaporthe oryzae that was important to glutamate homeostasis. MoGLT1 was constitutively expressed, but showed the highest expression level in appressoria. Deletion of MoGLT1 resulted in a significant reduction in conidiation and virulence. The ΔMoglt1 mutants were defective in appressorial penetration and the differentiation and spread of invasive hyphae in penetrated plant cells. The addition of exogenous glutamic acid partially rescued the defects of the ΔMoglt1 mutants in conidiation and plant infection. Assays for MoAtg8 expression and localization showed that the ΔMoglt1 mutants were defective in autophagy. The ΔMoglt1 mutants were delayed in the mobilization of glycogens and lipid bodies from conidia to developing appressoria. Taken together, our results show that glutamate synthase MoGlt1‐mediated glutamate homeostasis is important for pathogenesis and development in the rice blast fungus, possibly via the regulation of autophagy. [ABSTRACT FROM AUTHOR]

Rice false smut disease is an increasing threat to rice production in the world. Despite of best efforts, research for the infection of the fungus has yielded equivocal and conflicting results about where and how the infection is initiated and developed. Here we show a stepwise infection pattern and sophisticated regulation during this process. Initial infection occurred on the filaments, which prevented the production of mature pollen thus blocked the pollination. In the following days, the pathogen invaded the stigmas and styles, occasionally the ovaries. Expression analysis indicated that the fungus mimicked a successful fertilization process and enabled the continuous supply of nutrients for fungus to produce false smut balls. The stepwise infection of flower organs and mimicry of ovary fertilization unveiled in this study guided the rice plant into supplying nutrients for false smut ball development and represents a new and unique biological process of host pathogen interactions. [ABSTRACT FROM AUTHOR]

Triple whitlockite-type structure-based red phosphors Ca8MgBi1x(PO4)7:xEu3+ (x = 0.10, 0.20, 0.30, 0.40, 0.50, 0.60, 0.70, 0.80 and 1.00) were synthesized by a conventional solid-state reaction route and characterized by their X-ray crystal structures. The X-ray diffraction (XRD) patterns, Fourier transforminfrared spectra,morphologies, photoluminescence spectra, UV/Vis reflectance spectra, decay times and the International Commission on Illumination (CIE) chromaticity coordinates of Ca8MgBi1x (PO4)7:xEu3+ were analyzed. Eu-doped Ca8MgBi(PO4)7 phosphors exhibited strong red luminescence with peaks at 616nmdue to the 5Do-7 F2 electric dipole transition of Eu3+ ions after excitation at 396 nm. The UV/Vis spectra indicated that the band gap of Ca8MgBi0.30(PO4)7:0.70Eu3+ is larger than that of Ca8MgBi(PO4)7. The phosphor developed in this study has great potential as a red-light-emitting phosphor for UV light-emitting diodes. [ABSTRACT FROM AUTHOR]

RGA5-A, a component of the Pia resistance-protein complex (RGA4/RGA5-A) from Oryza sativa L. japonica, has the ability to interact physically with the effector protein AVR-Pia from Magnaporthe oryzae via its effector-interaction domain RGA5-A_S. The interaction between RGA5-A and AVR-Pia relieves the repression of RGA4, leading to AVR-independent cell death by the freed RGA4. To further understand the details of this interaction, the effector-interaction domain RGA5-A_S was expressed in Escherichia coli and purified to homogeneity. The purified recombinant protein His-RGA5-A_S was successfully crystallized using the sitting-drop vapour-diffusion method. A single crystal obtained using 0.2 M ammonium citrate, 25%( w/ v) PEG 3350 diffracted to 2.43 Å resolution. It belonged to space group P4122 or P4322, with unit-cell parameters a = b = 55.2, c = 78.2 Å, α = β = γ = 90°. [ABSTRACT FROM AUTHOR]

A series of single-phase full-color emitting Li2Sr1− x−ySiO4: xDy3+, yEu3+ phosphors were synthesized by solid-state reaction and characterized by X-ray diffraction and photoluminescence analyses. The samples showed emission peaks at 488 nm (blue), 572 nm (yellow), 592 nm (orange) and 617 nm (red) under 393 nm excitation. The photoluminescence excitation spectra, comprising the Eu-O charge transfer band and 4f-4f transition bands of Dy3+ and Eu3+, range from 200 to 500 nm. The Commission Internationale de I'Eclairage chromaticity coordinates for Li2Sr0.98− xSiO4:0.02Dy3+, xEu3+ phosphors were simulated. By manipulating Eu3+ and Dy3+ concentrations, the color points of Li2Sr1− x−ySiO4: xDy3+, yEu3+ were tuned from the greenish-white region to white light and eventually to reddish-white region, demonstrating that a tunable white light can be obtained by Li2Sr1− x−ySiO4: xDy3+, yEu3+ phosphors. Li2Sr0.98− xSiO4:0.02Dy3+, xEu3+ can serve as a white-light-emitting phosphor for phosphor-converted light-emitting diode. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A new mixed laser crystal, Yb0.005Y0.848Lu0.147VO4, has been successfully grown using the Czochralski method. An ICP-OES was used to measure the concentrations of elements (Yb, Y, Lu, V) in the crystal, and the chemical formula was determined. X-ray powder diffraction analysis shows that the crystal has ZrSiO4 structure. A pair of edge dislocations with certain orientation was observed by the HREM, and the orientation was confirmed by the calibration of the diffraction spots. The formation mechanism of this type dislocation was given by analysis on structure and thermal expansion of crystal. The suggestion to avoid these dislocations was also given. [ABSTRACT FROM AUTHOR]

Connective tissue growth factor (CTGF), a downstream mediator of transforming growth factor-β1 (TGF-β1) inducing fibrosis, has recently been implicated in peritoneal fibrosis. Extracellular matrix (ECM) accumulation and angiogenesis are characteristic changes in peritoneal fibrosis. In this study we investigated the effect of CTGF knockdown via interference RNA (RNAi) on ECM production and vascular endothelial growth factor (VEGF) expression induced by TGF-β1 in human peritoneal mesothelial cells (HPMCs). Four CTGF short hairpin RNA (shRNA) expression constructs were generated using the pRetroSuper vector, and infectious retroviral particles were prepared to infect HPMCs. Expression levels of CTGF, fibronectin(FN), collagen 1 (col 1), laminin, and VEGF mRNA and protein were measured by semi-quantitative reverse transcription polymerase chain reaction and western blot assay. CTGF expression was increased after stimulation with TGF-β1, but inhibited using each of the four independent CTGF shRNA constructs ( P < 0.01). Moreover, expression of ECM proteins (FN, col 1, and laminin) and VEGF were upregulated after incubation with TGF-β1, but elevated levels of ECM and VEGF induced by TGF-β1 were significantly inhibited by RNAi ( P < 0.01), but not by the empty retroviral vector ( P > 0.05). From these results, we concluded that retrovirus-mediated CTGF shRNA can effectively inhibit ECM production and VEGF expression induced by TGF-β1 in HPMCs. This study suggests that downregulation of CTGF may represent a potential therapeutic approach for peritoneal fibrosis through decreasing ECM accumulation and angiogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Although some studies have suggested that troglitazone could retard the progression of glomerulosclerosis, its effects on renal tubulointerstitial fibrosis have not been completely clarified. The aim of this study was to investigate the effects of troglitazone on the secretion of connective tissue growth factor (CTGF) and fibronectin (FN) in human renal proximal tubular epithelial (HK-2) cells induced by transforming growth factor-β1 (TGF-β1). The mRNA of CTGF and FN were measured by semi-quantitative RT-PCR. CTGF and FN protein were detected by Western blot and ELISA, respectively. Our results revealed that troglitazone could inhibit CTGF and FN expression in a dose-dependent manner in human renal proximal tubular epithelial cells induced by TGF-β1, which may be one of the mechanisms of troglitazone contributing to retard the progression of renal tubulointerstitial fibrosis. [Copyright &y& Elsevier]

Background: Among those with heart failure (HF), women are more likely to develop depression than men. Few studies have focused on the outcomes of female patients with HF with depressive symptoms., Methods and Results: A total of 506 female patients with HF with preserved ejection fraction were included in this secondary analysis from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) cohort, and 439 female patients with HF with reduced ejection fraction were included from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) cohort. Depressive symptoms were measured using the Patient Health Questionnaire-9 and Beck Depression Inventory-II. The depression class was categorized by severity, and the change in clinical depression class was defined as aggravated (1-grade increase) or improved (1-grade decrease). The prognostic value of depressive symptoms was determined by using multivariable Cox proportional hazards models. Female patients with improved depressive symptoms had worse depressive status at baseline and lower baseline Kansas City Cardiomyopathy Questionnaire scores. Depression class at the 12-month visit and depression class change were the dominant prognostic factors for cardiovascular death in female patients with HF with preserved ejection fraction (hazard ratio [HR], 1.43 [95% CI, 1.02-2.01], P =0.036; HR, 1.71 [95% CI, 1.14-2.55], P =0.009). Among the patients with HF with reduced ejection fraction, both the depression class at baseline and depression class change had significant prognostic effects on cardiovascular death (HR, 3.30 [95% CI, 1.70-6.39], P <0.001; HR, 2.21 [95% CI, 1.28-3.80], P =0.004). However, the prognostic value of depressive assessments for hospitalization in patients with HF is unclear., Conclusions: In female patients with HF with reduced ejection fraction, the depression class at baseline was most strongly associated with cardiovascular death, whereas in female patients with HF with preserved ejection fraction, the change in depression class exhibited a more significant prognostic trend.

Background: Human papillomavirus (HPV) infections are associated with cervical cancer. There were only a few reports and detailed data about epidemiological research of HPV infection in general population of China., Aims: To determine the prevalence of genital HPV infection in Chinese women of Guangdong province., Methods: A total of 1705 women were screened by gene chip. All HPV-positive women were further examined by ThinPrep liquid-based cytology test (TCT), and the cervical biopsies of those women with positive HPV-DNA and abnormal TCT were collected for pathological diagnosis., Results: The overall HPV prevalence was 9.03% (154 of 1705), and 72.3% (126 of 154) of total positive samples were high-risk types, with higher prevalence of types 52, 58, 16, 18 and CP8304. For women aged 51 years or older, the overall high-risk HPV prevalence was 12.2% (24 of 179), which was obviously higher than those of other age groups (P < 0.05)., Conclusions: Our results showed that the HPV prevalence in Guangdong is very similar to the world level. Unlike most previous studies, our findings suggest that HPV prevalence increased with age, and that the predominant genotypes in this area were HPV 52 and 58.