Fine mapping and transcriptome profiling reveal CpAPRR2 to modulate immature fruit rind color formation in zucchini (Cucurbita pepo).

KEY MESSAGE: A large fragment deletion of CpAPRR2, encoding a two-component response regulator-like protein, which influences immature white rind color formation in zucchini (Cucurbita pepo). Fruit rind color is an important agronomic trait that affects commodity quality and consumer choice in zucchini (Cucurbita pepo). However, the molecular mechanism controlling rind color is unclear. We characterized two zucchini inbred lines: '19' (dark green rind) and '113' (white rind). Genetic analysis revealed white immature fruit rind color to be controlled by a dominant locus (CpW). Combining bulked segregant analysis sequencing (BSA-seq) and Kompetitive Allele-Specific PCR (KASP) markers, we mapped the CpW locus to a 100.4 kb region on chromosome 5 and then narrow down the candidate region to 37.5 kb using linkage analysis of 532 BC1 and 1613 F2 individuals, including 6 coding genes. Among them, Cp4.1LG05g02070 (CpAPRR2), encoding a two-component response regulator-like protein, was regarded to be a promising candidate gene. The expression level of CpAPRR2 in dark green rind was significantly higher than that in white rind and was induced by light. A deletion of 2227 bp at the 5' end of CpAPRR2 in '113' might explain the white phenotype. Further analysis of allelic diversity in zucchini germplasm resources revealed rind color to be associated with the deletion of CpAPRR2. Subcellular localization analysis indicated that CpAPRR2 was a nuclear protein. Transcriptome analysis using near-isogenic lines with dark green (DG) and white (W) rind indicated that genes involved in photosynthesis and porphyrin metabolism pathways were enriched in DG compared with W. Additionally, chlorophyll synthesis-related genes were upregulated in DG. These results identify mechanisms of zucchini rind color and provide genetic resources for breeding.

NIR-IIb fluorescence antiangiogenesis copper nano-reaper for enhanced synergistic cancer therapy.

The formation of blood vessel system under a relatively higher Cu2+ ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in forming the tumor immune microenvironment. Herein, a copper ions nano-reaper (LMDFP) is rationally designed not only for chelating copper ions in tumors, but also for combination with photothermal therapy (PTT) to improve antitumor efficiency. Under 808 nm laser irradiation, the fabricated nano-reaper converts light energy into thermal energy to kill tumor cells and promotes the release of D-penicillamine (DPA) in LMDFP. Photothermal properties of LMDFP can cause tumor ablation in situ, which further induces immunogenic cell death (ICD) to promote systematic antitumor immunity. The released DPA exerts an anti-angiogenesis effect on the tumor through chelating copper ions, and inhibits the expression of programmed death ligand 1 (PD-L1), which synergizes with PTT to enhance antitumor immunity and inhibit tumor metastasis. Meanwhile, the nanoplatform can emit near-infrared-IIb (NIR-IIb) fluorescence under 980 nm excitation, which can be used to track the nano-reaper and determine the optimal time point for PTT. Thus, the fabricated nano-reaper shows powerful potential in inhibiting tumor growth and metastasis, and holds great promise for the application of copper nanochelator in precise tumor treatment.

Structural and mechanistic insights into the complexes formed by Wolbachia cytoplasmic incompatibility factors.

Wolbachia bacteria, inherited through the female germ line, infect a large fraction of arthropod species. Many Wolbachia strains manipulate host reproduction, most commonly through cytoplasmic incompatibility (CI). CI, a conditional male sterility, results when Wolbachia-infected male insects mate with uninfected females; viability is restored if the female is similarly infected (called "rescue"). CI is used to help control mosquito-borne viruses such as dengue and Zika, but its mechanisms remain unknown. The coexpressed CI factors CifA and CifB form stable complexes in vitro, but the timing and function of this interaction in the insect are unresolved. CifA expression in the female germ line is sufficient for rescue. We report high-resolution structures of a CI-factor complex, CinA-CinB, which utilizes a unique binding mode between the CinA rescue factor and the CinB nuclease; the structures were validated by biochemical and yeast growth analyses. Importantly, transgenic expression in Drosophila of a nonbinding CinA mutant, designed based on the CinA-CinB structure, suggests CinA expressed in females must bind CinB imported by sperm in order to rescue embryonic viability. Binding between cognate factors is conserved in an enzymatically distinct CI system, CidA-CidB, suggesting universal features in Wolbachia CI induction and rescue.

PDGFB-targeted functional MRI nanoswitch for activatable T1-T2 dual-modal ultra-sensitive diagnosis of cancer.

As one of the most significant imaging modalities currently available, magnetic resonance imaging (MRI) has been extensively utilized for clinically accurate cancer diagnosis. However, low signal-to-noise ratio (SNR) and low specificity for tumors continue to pose significant challenges. Inspired by the distance-dependent magnetic resonance tuning (MRET) phenomenon, the tumor microenvironment (TME)-activated off-on T1-T2 dual-mode MRI nanoswitch is presented in the current study to realize the sensitive early diagnosis of tumors. The tumor-specific nanoswitch is designed and manufactured on the basis of PDGFB-conjugating ferroferric oxide coated by Mn-doped silica (PDGFB-FMS), which can be degraded under the high-concentration GSH and low pH in TME to activate the T1-T2 dual-mode MRI signals. The tumor-specific off-on dual-mode MRI nanoswitch can significantly improve the SNR and is used successfully for the accurate diagnosis of early-stage tumors, particularly for orthotopic prostate cancer. In addition, the systemic delivery of the nanoswitch did not cause blood or tissue damage, and it can be excreted out of the body in a timely manner, demonstrating excellent biosafety. Overall, the strategy is a significant step in the direction of designing off-on dual-mode MRI nanoprobes to improve imaging accuracy, which opens up new avenues for the development of new MRI probes.

Efficacy and Safety of Distal Radial Artery Approach for Coronary Angiography: A Retrospective Study.

BACKGROUND: The distal radial artery approach has been employed as a potential alternative technique for coronary angiography. Nevertheless, its clinical implementation is significantly constrained by the narrow diameter of the radial artery. A comprehensive investigation of the efficacy and safety of the distal radial artery approach for coronary angiography is lacking. The objective of this study is to investigate the impact of the distal radial artery approach for coronary angiography and transradial artery access for interventional diagnosis and treatment. In addition, the effectiveness and safety of the distal radial artery approach for coronary artery angiography will be analyzed, for the wider adoption of this technique in clinical practice. METHODS: A total of 68 patients with coronary heart disease (CHD) who underwent coronary catheterization via the left distal radial artery approach from December 2020 to December 2022 using the Distal radial artery approach (TRA) comprised the case-control study group. Seventy-three CHD patients who underwent routine left Transradial Artery Access coronary catheterization were selected as the Regular TRA group during the same period. Clinical data including age, body mass index (BMI), gender, CHD risk factors, routine drug treatment, ultrasonic-related indicators and operation-related indicators were collected from electronic medical records and the catheterization database from the two groups of patients. RESULTS: The diameter and Endothelium-dependent vasodilation (noe FMD) of puncture vessels in the Distal TRA group were significantly lower than those in the Regular radial artery approach (TRA) group (p-value < 0.05). After a period of 48 hours following the catheterization, the puncture vessel diameter and flow-mediated dilation (FMD) of the Distal TRA group were significantly lower compared to those of the Regular TRA group (p-value < 0.05). The effectiveness of transradial artery access was then compared between the two groups. It was determined that the Distal TRA group exhibited significantly higher values in terms of the Visual Analog Scale (VAS) score, puncture time, and heparin usage, in comparison to the Regular TRA group (p-value < 0.05). The occurrence rates of local hematoma, mediastinal hematoma, retroperitoneal hematoma, pseudoaneurysm, arteriovenous fistula, vagal reflex, vasospasm, blood transfusion, and other complications among patients in the Distal TRA group were comparable to those in the Regular TRA group (p-value > 0.05). The incidence of puncture and X-ray radiation in the Distal TRA group was found to be marginally higher compared to the Regular TRA group. This study suggests that the safety profile of patients undergoing coronary artery catheterization via the distal radial artery is relatively higher than those undergoing the procedure via the transradial artery, although the difference was not statistically significant (p-value > 0.05). CONCLUSIONS: The Distal radial artery approach can be used for conducting comprehensive coronary interventional diagnosis and treatment procedures, offering benefits such as reduced postoperative compression time, better hemostasis through the distal radial artery approach, and enhanced patient comfort. This approach demonstrates favorable efficacy and safety, making it a suitable routine puncture method for clinical treatment.

Protective effect of dihydromyricetin on vascular smooth muscle cell apoptosis induced by hydrogen peroxide in rats.

OBJECTIVE: Dihydromyricetin (DMY), also called Ampelopsin, which was extracted from Ampelopsis grossedentata, has been demonstrated to have a protective effect against cell oxidative injury and cell apoptosis in vitro. In the present study, we tried to study the role of DMY on apoptosis of vascular smooth muscle cells (VSMCs) induced by hydrogen peroxide (H2O2) and explore the underlying mechanisms. METHODS: Apoptotic cells were detected by Hematoxylin and Eosin (H.E.) staining, Hoechst 33342 staining, and Annexin V-fluorescein isothiocyanate binding assay. The intracellular reactive oxygen species (ROS) level was estimated through fluorescence assay. The mRNA and protein expression of Caspase-3, Caspase-9, Bcl-2, and Bax were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. RESULTS: The results showed that the pretreatment of VSMCs with DMY not only significantly increased cell viability, reduced intracellular ROS release, alleviated the morphological changes of apoptosis, and decreased the apoptosis rate, but also upregulated Bcl-2 expression and downregulated Caspase-3, Caspase-9, Bax expression, and ultimately attenuated the H2O2-stimulated apoptosis. CONCLUSION: The inhibition of DMY on VSMC apoptosis may be mediated by ROS scavenging and the activation of the mitochondrial apoptotic signaling pathway.

Alterations in the spatiotemporal expression of the chemokine receptor CXCR4 in endothelial cells cause failure of hierarchical vascular branching.

The C-X-C chemokine receptor CXCR4 and its ligand CXCL12 play an important role in organ-specific vascular branching morphogenesis. CXCR4 is preferentially expressed by arterial endothelial cells, and local secretion of CXCL12 determines the organotypic pattern of CXCR4+ arterial branching. Previous loss-of-function studies clearly demonstrated that CXCL12-CXCR4 signaling is necessary for proper arterial branching in the developing organs such as the skin and heart. To further understand the role of CXCL12-CXCR4 signaling in organ-specific vascular development, we generated a mouse model carrying the Cre recombinase-inducible Cxcr4 transgene. Endothelial cell-specific Cxcr4 gain-of-function embryos exhibited defective vascular remodeling and formation of a hierarchical vascular branching network in the developing skin and heart. Ectopic expression of CXCR4 in venous endothelial cells, but not in lymphatic endothelial cells, caused blood-filled, enlarged lymphatic vascular phenotypes, accompanied by edema. These data suggest that CXCR4 expression is tightly regulated in endothelial cells for appropriate vascular development in an organ-specific manner.

Ubiquitous expression of Akt1 p.(E17K) results in vascular defects and embryonic lethality in mice.

Proteus syndrome is a progressive overgrowth disorder with vascular malformations caused by mosaic expression of the AKT1 c.49G > A, p.(E17K) activating variant which was predicted to cause lethality if expressed ubiquitously. To test that hypothesis, we used the ACTB-Cre gene to activate a conditional Akt1 p.(E17K) allele in the mouse. No offspring that was heterozygous for both Cre and the conditional allele (ßA-Akt1WT/flx) was viable. Fewer than expected numbers of ßA-Akt1WT/flx embryos were seen beginning at E11.5, but a few survived until E17.5. The phenotype ranged from mild to severe, but generally ßA-Akt1WT/flx embryos had fewer visible blood vessels and more hemorrhages than their wild-type littermates, which was suggestive of a vascular abnormality. Examination of E13.5 limb skin showed a primitive capillary network with increased branching complexity and abnormal patterning compared with wild-type skin. By E15.5, wild-type skin had undergone angiogenesis and formed a hierarchical network of remodeled vessels, whereas in ßA-Akt1WT/flx embryos, the capillary network failed to remodel. Mural cell coverage of the blood vessels was also reduced in ßA-Akt1WT/flx skin compared with that of wild type. Restricting expression of Akt1E17K to endothelial, cardiac or smooth muscle cells resulted in viable offspring and remodeled vasculature and did not recapitulate the ßA-Akt1WT/flx phenotype. We conclude that ubiquitous expression of Akt1E17K suppresses remodeling and inhibits the formation of a normal skin vasculature. We postulate that this failure prevents proper circulation necessary to support the growing embryo and that it is the result of interactions of multiple cell types with increased AKT signaling.

NIR-II Fluorescence Imaging-Guided Oxygen Self-Sufficient Nano-Platform for Precise Enhanced Photodynamic Therapy.

Tumor hypoxia and systemic toxicity seriously affect the efficacy of photodynamic therapy (PDT) and are considered as the "Achilles' heel" of PDT. Herein, to combat such limitations, an intelligent orthogonal emissions LDNP@SiO2 -CaO2 and folic acid-polyethylene glycol-Ce6 nanodrug is rationally designed and fabricated not only for relieving the hypoxic tumor microenvironment (TME) to enhance PDT efficacy, but also for determining the optimal triggering time through second near-infrared (NIR-II) fluorescence imaging. The designed nanodrug continuously releases a large amount of O2 , H2 O2 , and Ca2+ ions when exposed to the acidic TME. Meanwhile, under downshifting NIR-II bioimaging guidance, chlorine e6 (Ce6) consumes oxygen to produce 1 O2 upon excitation of upconversion photon. Moreover, cytotoxic reactive oxygen species (ROS) and calcium overload can induce mitochondria injury and thus enhance the oxidative stress in tumor cells. As a result, the NIR-II bioimaging guided TME-responsive oxygen self-sufficient PDT nanosystem presents enhanced anti-tumor efficacy without obvious systemic toxicity. Thus, the fabricated nanodrug offers great potential for designing an accurate cancer theranostic system.

Iron redistribution induces oxidative burst and resistance in maize against Curvularia lunata.

MAIN CONCLUSION: ΔClnps6 induced iron redistribution in maize B73 leaf cells and resulted in reactive oxygen species (ROS) burst to enhance plant resistance against Curvularia lunata. Iron is an indispensable co-factor of various crucial enzymes that are involved in cellular metabolic processes and energy metabolism in eukaryotes. For this reason, plants and pathogens compete for iron to maintain their iron homeostasis, respectively. In our previous study, ΔClnps6, the extracellular siderophore biosynthesis deletion mutant of Curvularia lunata, was sensitive to exogenous hydrogen peroxide and virulence reduction. However, the mechanism was not studied. Here, we report that maize B73 displayed highly resistance to ΔClnps6. The plants recruited more iron at cell wall appositions (CWAs) to cause ROS bursts. Intracellular iron deficiency induced by iron redistribution originated form up-regulated expression of genes involved in intracellular iron consumption in leaves and absorption in roots. The RNA-sequencing data also showed that the expression of respiratory burst oxidase homologue (ZmRBOH4) and NADP-dependent malic enzyme 4 (ZmNADP-ME4) involved in ROS production was up-regulated in maize B73 after ΔClnps6 infection. Simultaneously, jasmonic acid (JA) biosynthesis genes lipoxygenase (ZmLOX), allene oxide synthase (ZmAOS), GA degradation gene gibberellin 2-beta-dioxygenase (ZmGA2OX6) and ABA degradation genes abscisic acid hydroxylase (ZmABH1, ZmABH2) involved in iron homeostasis were up-regulated expression. Ferritin1 (ZmFER1) positive regulated maize resistance against C. lunata via ROS burst under Fe-limiting conditions. Overall, our results showed that iron played vital roles in activating maize resistance in B73-C. lunata interaction.

Fine mapping of powdery mildew resistance gene MlWE74 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides) in an NBS-LRR gene cluster.

KEY MESSAGE: Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars.

Diffraction gratings based on a multilayer silicon nitride waveguide with high upward efficiency and large effective length.

Diffraction gratings with high upward diffraction efficiency and large effective length are required for chip-scale light detection and ranging. We propose a diffraction grating based on a multilayer silicon nitride waveguide, which theoretically achieves an upward diffraction efficiency of 92%, a near-field effective length of 376 µm, and a far-field divergence angle of 0.105° at a wavelength of 850 nm. The diffraction grating has a high tolerance to process variations based on Monte Carlo analysis. When the conditions are ±5% layer thickness variation, ±50nm lithographic variation, and ±20nm wavelength drift, more than 71% of the grating samples have a diffraction efficiency higher than 80%, and 100% of the samples have an effective length larger than 200 µm (corresponding to a far-field divergence <0.2∘). Furthermore, the near-field effective length of the grating with an upward diffraction efficiency above 90% can be adjusted from hundreds of microns to centimeters by changing the etching layer thickness and the grating duty cycle. This diffraction grating has a potential application in optical sensing and imaging from visible to near-IR wavelengths.

A Retrospective Study of Parietal Lobe Epilepsy: Functional Anatomy and Surgical Treatment.

Context: Parietal lobe epilepsy (PLE) accounts for approximately 5% of all focal epilepsies worldwide,1 and few PLE patients have undergone epilepsy surgery in the past. With the introduction of functional neuroimaging methods, such as interictal fluorodeoxyglucose-positron emission tomography (FDG-PET), stereotactic electroencephalograms (SEEGs), and high-resolution magnetic resonance imaging (MRI), more patients with intractable neocortical epilepsy have been considered for surgical treatment. Objective: The study intended to characterize the clinical features, aura, and presurgical evaluations of patients with PLE, by investigating their demographic and clinical characteristics, and to evaluate the prognostic value of the four diagnostic modalities-MRI, FDG-PET, scalp EEG, and SEEG-in terms of the localization of epileptogenic area. Design: The research team performed a retrospective analysis of outcomes for PLE patients who underwent resistive brain surgery. Setting: The study took place in the Neurosurgery Department of Epilepsy at the Second Hospital of Hebei Medical University in Shijiazhuang, China. Participants: Participants were 9 PLE patients, 4 males and 5 females, who underwent epilepsy surgery at the hospital between 2017 and 2019. Outcome Measures: The measures included demographic data, seizure data, electroencephalogram (EEG) recordings, magnetic resonance imaging (MRI) of the brain, positron emission tomography (PET), and stereotactic electroencephalogram (SEEG). The pathological findings were reviewed. Results: The five participants who had a PET all had positive results. Eight participants who had parietal lobe lesions had an MRI, and four had a stereotactic electroencephalogram (SEEG) that localized the epileptogenic zone. The interictal scalp EEG recordings for seven participants showed an abnormality, and six participants who had ictal surface EEG recordings showed parietal ictal EEG onset. Conclusions: Surgical excision of epileptogenic foci is the main treatment for drug-resistant PLE. Parietal functional anatomy is the basis for understanding and diagnosing PLE. Aura, semiology, interictal EEG, and PET are an important foundation for evaluation of PLE patients, and the SEEG is the most valuable tool, allowing localization of the epileptogenic zone.

Genome-Wide Identification and Characterization of Members of the ACS Gene Family in Cucurbita maxima and Their Transcriptional Responses to the Specific Treatments.

Ethylene biosynthesis and signal transduction play critical roles in plant sex differentiation. ACS (1-aminocyclopropane-1-carboxylic acid synthase) is a rate-limiting enzyme in ethylene biosynthesis. However, the understanding of the ACS gene family in Cucurbita maxima is limited. Here, we identified and characterized 13 ACS genes in the C. maxima genome. All ACS genes could be divided into three groups according to a conserved serine residue at the C-terminus. Thirteen CmaACS genes were found to be randomly distributed on 10 of the 20 chromosomes of C. maxima. The ACS gene exhibits different tissue-specific expression patterns in pumpkin, and four ACS genes (CmaACS1, CmaACS4, CmaACS7, and CmaACS9) were expressed specifically in both the female and male flowers of C. maxima. In addition, the expression levels of CmaACS4 and CmaACS7 were upregulated after ethephon and IAA treatments, which ultimately increased the number of female flowers, decreased the position of the first female flower and decreased the number of bisexual flowers per plant. These results provide relevant information for determining the function of the ACS genes in C. maxima, especially for regulating the function of ethylene in sex determination.

Resective epilepsy surgery in tuberous sclerosis complex: a nationwide multicentre retrospective study from China.

At least 50% of patients with tuberous sclerosis complex present with intractable epilepsy; for these patients, resective surgery is a treatment option. Here, we report a nationwide multicentre retrospective study and analyse the long-term seizure and neuropsychological outcomes of epilepsy surgery in patients with tuberous sclerosis complex. There were 364 patients who underwent epilepsy surgery in the study. Patients' clinical data, postoperative seizure outcomes at 1-, 4-, and 10-year follow-ups, preoperative and postoperative intelligence quotients, and quality of life at 1-year follow-up were collected. The patients' ages at surgery were 10.35 ± 7.70 years (range: 0.5-47). The percentage of postoperative seizure freedom was 71% (258/364) at 1-year, 60% (118/196) at 4-year, and 51% (36/71) at 10-year follow-up. Influence factors of postoperative seizure freedom were the total removal of epileptogenic tubers and the presence of outstanding tuber on MRI at 1- and 4-year follow-ups. Furthermore, monthly seizure (versus daily seizure) was also a positive influence factor for postoperative seizure freedom at 1-year follow-up. The presence of an outstanding tuber on MRI was the only factor influencing seizure freedom at 10-year follow-up. Postoperative quality of life and intelligence quotient improvements were found in 43% (112/262) and 28% (67/242) of patients, respectively. Influence factors of postoperative quality of life and intelligence quotient improvement were postoperative seizure freedom and preoperative low intelligence quotient. The percentage of seizure freedom in the tuberectomy group was significantly lower compared to the tuberectomy plus and lobectomy groups at 1- and 4-year follow-ups. In conclusion, this study, the largest nationwide multi-centre study on resective epilepsy surgery, resulted in improved seizure outcomes and quality of life and intelligence quotient improvements in patients with tuberous sclerosis complex. Seizure freedom was often achieved in patients with an outstanding tuber on MRI, total removal of epileptogenic tubers, and tuberectomy plus. Quality of life and intelligence quotient improvements were frequently observed in patients with postoperative seizure freedom and preoperative low intelligence quotient.

Tubule-Specific Mst1/2 Deficiency Induces CKD via YAP and Non-YAP Mechanisms.

BACKGROUND: The serine/threonine kinases MST1 and MST2 are core components of the Hippo pathway, which has been found to be critically involved in embryonic kidney development. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the pathway's main effectors. However, the biologic functions of the Hippo/YAP pathway in adult kidneys are not well understood, and the functional role of MST1 and MST2 in the kidney has not been studied. METHODS: We used immunohistochemistry to examine expression in mouse kidneys of MST1 and MST2, homologs of Hippo in Drosophila. We generated mice with tubule-specific double knockout of Mst1 and Mst2 or triple knockout of Mst1, Mst2, and Yap. PCR array and mouse inner medullary collecting duct cells were used to identify the primary target of Mst1/Mst2 deficiency. RESULTS: MST1 and MST2 were predominantly expressed in the tubular epithelial cells of adult kidneys. Deletion of Mst1/Mst2 in renal tubules increased activity of YAP but not TAZ. The kidneys of mutant mice showed progressive inflammation, tubular and glomerular damage, fibrosis, and functional impairment; these phenotypes were largely rescued by deletion of Yap in renal tubules. TNF-α expression was induced via both YAP-dependent and YAP-independent mechanisms, and TNF-α and YAP amplified the signaling activities of each other in the tubules of kidneys with double knockout of Mst1/Mst2. CONCLUSIONS: Our findings show that tubular Mst1/Mst2 deficiency leads to CKD through both the YAP and non-YAP pathways and that tubular YAP activation induces renal fibrosis. The pathogenesis seems to involve the reciprocal stimulation of TNF-α and YAP signaling activities.

Identification and fine mapping of spot blotch (Bipolaris sorokiniana) resistance gene Sb4 in wheat.

KEY MESSAGE: A new spot blotch (Bipolaris sorokiniana) resistance gene Sb4 was mapped in a genomic interval of 1.34 Mb on wheat chromosome 4BL. Spot blotch, caused by Bipolaris sorokiniana, has emerged as a serious concern for cultivation of wheat in warmer and humid regions of the world, which results in substantial yield losses and descends with quality. In this study, we identified and mapped a spot blotch resistance gene, designated as Sb4, against B. sorokiniana in wheat. Bulked segregant RNA-Seq (BSR-Seq) analysis and single-nucleotide polymorphism mapping showed that Sb4 is located on the long arm of chromosome 4B. A genetic linkage map of Sb4 was constructed using an F4 mapping population developed from the cross between 'GY17' and 'Zhongyu1211,' and Sb4 was delimited in a 7.14-cM genetic region on 4BL between markers B6811 and B6901. Using the Chinese Spring reference sequences of chromosome arm 4BL, 13 new polymorphic markers were developed. Finally, Sb4 was mapped in a 1.19-cM genetic interval corresponding to a 1.34-Mb physical genomic region of Chinese Spring chromosome 4BL containing 21 predicted genes. This study provides a foundational step for further cloning of Sb4 using a map-based approach.

Organoaluminum Compounds as Catalysts for Monohydroboration of Carbodiimides.

The effective catalytic activity of organoaluminum compounds for the monohydroboration of carbodiimides has been demonstrated. Two aluminum complexes, 2 and 3, were synthesized and characterized. The efficient catalytic performances of four aluminum hydride complexes L1 AlH2 (L1 =HC(CMeNAr)2 , Ar=2,6-Et2 C6 H3 ; 1), L2 AlH2 (NMe3 ) (L2 =o-C6 H4 F(CH=N-Ar), Ar=2,6-Et2 C6 H3 ; 2), L3 AlH (L3 =2,6-bis(1-methylethyl)-N-(2-pyridinylmethylene)phenylamine; 3), and L4 AlH(NMe3 ) (L4 =o-C6 H4 (N-Dipp)(CH=N-Dipp), Dipp=2,6-iPr2 C6 H3 ; 4), and an aluminum alkyl complex L1 AlMe2 (5) were used for the monohydroboration of carbodiimides investigated under solvent-free and mild conditions. Compounds 1-3 and 5 can produce monohydroborated N-borylformamidine, whereas 4 can afford the C-borylformamidine product. A suggested mechanism of this reaction was explored, and the aluminum formamidinate compound 6 was characterized by single-crystal X-ray, also a stoichiometric reaction was investigated.

Synthesis of Cyclic Alkyl(amino) Carbene Stabilized Silylenes with Small N-Donating Substituents.

Lewis base cAACs stabilized monomeric silylenes with halogen or methyl substituents at the silicon center have not been reported due to the strong σ-donor and π-acceptor character of cAAC. To prepare these monomeric silylenes, we used the silicon(IV) precursors 5 and 6 with a nitrogen donor group L (L=o-C6 H4 NMe2 ). The cAAC-stabilized (cAAC=C(CH2 )(CMe2 )2 N-Ar, Ar=2,6-iPr2 C6 H3 ) silylenes LSiCl(cAAC) (7) and LSiMe(cAAC) (8) were synthesized by reduction of LSiCl3 and LSiMeCl2 with two equivalents of KC8 in the presence of one equivalent of cAAC, respectively. Compounds 7 and 8 were characterized by single-crystal X-ray crystallography, NMR spectroscopy, and elemental analysis. Compounds 7 and 8 are stable in the solid state as well as in solution at room temperature for at least four months under inert conditions.

Methylene Blue Exerts Anticonvulsant and Neuroprotective Effects on Self-Sustaining Status Epilepticus (SSSE) Induced by Prolonged Basolateral Amygdala Stimulation in Wistar Rats.

BACKGROUND This study was designed to investigate the potential anticonvulsant and neuroprotective effects of methylene blue (MB) on self-sustaining status epilepticus (SSSE) induced by prolonged basolateral amygdala stimulation (BLA) in Wistar rats. MATERIAL AND METHODS The rats were randomly divided into 4 groups: (1) the Control group (rats without any treatment); (2) the Sham group (rats received electrode implantation but without electrical stimulation); (3) the SSSE group (rats received electrode implantation and additional electrical stimulation); and (4) the SSSE+MB group (rats received 1 mg/kg MB intraperitoneal injection 5 min after SSSE). SSSE models were established by prolonged BLA stimulation. The severities of SSSE were assessed by the number of separate seizures and the accumulated time of seizures. The variations of malondialdehyde/glutathione (MDA/GSH) were assessed 24 h after the establishment of SSSE. Nissl staining was performed to detect the surviving neurons in hippocampal CA1 and CA3 regions, and Western blotting assays were used to detect Caspase-3 (CASP3), B cell lymphoma 2 (BCL2), and BCL2-associated X protein (BAX). RESULTS Compared with the SSSE group, treatment with MB (1) markedly reduced the number and accumulated time of seizure activities; (2) significantly attenuated the increase of MDA and the decrease of GSH hippocampal levels; (3) markedly improved the cell morphology and alleviated the neuronal loss in hippocampal CA1 and CA3 regions; (4) significantly attenuated the increase of CASP3 and BAX and the decrease of BCL2 hippocampal levels. CONCLUSIONS MB has a protective effect in the SSSE model and may be useful as an adjuvant for preventing or treating epilepsy in humans.