Retraction of "Ravoxertinib Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage through Early Inhibition of Erk1/2".

[This retracts the article DOI: 10.1021/acsomega.3c01296.].

Corrigendum: TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis after experimental subarachnoid hemorrhage.

[This corrects the article DOI: 10.3389/fncel.2022.878673.].

A perennial living mulch system fosters a more diverse and balanced soil bacterial community.

Cover crops are known to positively impact soil health, both at a physical level (through erosion control and organic matter enhancement) and at a biological level (by fostering more diverse microbial communities). However, most research in this area has been conducted in the context of annual cover crops that are terminated when the main crop is planted. We have previously demonstrated that a continuous "living mulch" cover crop system can enhance the physical and chemical aspects of soil health; In this study, we reveal its effect on the soil bacterial community and compare it to two different annual cover crops and a conventional control without cover crops. We examined the effect of a living-mulch (LM) system using perennial white clover (Trifolium pratense L), annual cereal rye (Secale cereale L.) (CR), annual crimson clover (Trifolium incarnatum L.) (CC), and a no-cover (NC) control at three time points during the 2018 growing season. 16S rRNA amplicon analysis of the soil bacterial community revealed that the community composition in cover crop systems was significantly different from the NC control, and that LM and CR accommodated more heterogeneous and even bacterial communities compared to the NC control. The difference in bacterial composition between cover crop systems appears to be partly influenced by soil nitrogen concentration and lime buffer capacity. Overall community diversity was associated with nitrogen and metal ion concentrations, and these associations were both stronger and more numerous later in the season. These results elucidate how a perennial cover crop system affects the soil bacterial community and advance our understanding of the interactions between crops, management practices, and soil microbiomes in sustainable agriculture.

Ravoxertinib Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage through Early Inhibition of Erk1/2.

Extracellular signal-regulated kinase 1 and 2 (Erk1/2) signaling has been shown to be involved in brain injury after subarachnoid hemorrhage (SAH). A first-in-human phase I study reported that ravoxertinib hydrochloride (RAH), a novel Erk1/2 inhibitor, has an acceptable safety profile and pharmacodynamic effects. Here, we showed that the level of Erk1/2 phosphorylation (p-Erk1/2) was significantly increased in the cerebrospinal fluid (CSF) of aneurysmal subarachnoid hemorrhage (aSAH) patients who developed poor outcomes. In a rat SAH model that was produced by the intracranial endovascular perforation method, western blot observed that the level of p-Erk1/2 was also increased in the CSF and basal cortex, showing a similar trend with aSAH patients. Immunofluorescence and western blot indicated that RAH treatment (i.c.v injection, 30 min post-SAH) attenuates the SAH-induced increase of p-Erk1/2 at 24 h in rats. RAH treatment can improve experimental SAH-induced long-term sensorimotor and spatial learning deficits that are evaluated by the Morris water maze, rotarod test, foot-fault test, and forelimb placing test. Moreover, RAH treatment attenuates neurobehavioral deficits, the blood-brain barrier damage, and cerebral edema at 72 h after SAH in rats. Furthermore, RAH treatment decreases the SAH-elevated apoptosis-related factor active caspase-3 and the necroptosis-related factor RIPK1 expression at 72 h in rats. Immunofluorescence analysis showed that RAH attenuated neuronal apoptosis but not neuronal necroptosis in the basal cortex at 72 h after SAH in rats. Altogether, our results suggest that RAH improves long-term neurologic deficits through early inhibition of Erk1/2 in experimental SAH.

Variation in the fruit development gene POINTED TIP regulates protuberance of tomato fruit tip.

The domestication of tomato has led to striking variations in fruit morphology. Here, we show a genome-wide association study (GWAS) to understand the development of the fruit tip and describe a POINTED TIP (PT) gene that encodes a C2H2-type zinc finger transcription factor. A single nucleotide polymorphism is found to change a histidine (H) to an arginine (R) in the C2H2 domain of PT and the two alleles are referred to as PTH and PTR. Knocking out PTH leads to development of pointed tip fruit. PTH functions to suppress pointed tip formation by downregulating the transcription of FRUTFULL 2 (FUL2), which alters the auxin transport. Our evolutionary analysis and previous studies by others suggest that the PTR allele likely hitch-hiked along with other selected loci during the domestication process. This study uncovers variation in PT and molecular mechanism underlying fruit tip development in tomato.

Genome-wide association mapping of resistance to the sorghum aphid in Sorghum bicolor.

Since 2013, the sorghum aphid (SA), Melanaphis sorghi (Theobald), has been a serious pest that hampers all types of sorghum production in the U.S. Known sorghum aphid resistance in sorghum is limited to a few genetic regions on SBI-06. In this study, a subset of the Sorghum Association Panel (SAP) was used along with some additional lines to identify genomic regions that confer sorghum aphid resistance. SAP lines were grown in the field and visually evaluated for SA resistance during the growing seasons of 2019 and 2020 in Tifton, GA. In 2020, the SAP accessions were also evaluated for SA resistance in the field using drone-based high throughput phenotyping (HTP). Flowering time was recorded in the field to confirm that our methods were sufficient for identifying known quantitative trait loci (QTL). This study combined phenotypic data from field-based visual ratings and reflectance data to identify genome-wide associated (GWAS) marker-trait associations (MTA) using genotyping-by-sequencing (GBS) data. Several MTAs were identified for SA-related traits across the genome, with a few common markers that were consistently identified on SBI-08 and SBI-10 for aphid count and plant damage, as well as loci for reflectance-based traits on SBI-02, SBI-03, and SBI-05. Candidate genes encoding leucine-rich repeats (LRR), Avr proteins, lipoxygenases (LOXs), calmodulins (CAM) dependent protein kinase, WRKY transcription factors, flavonoid biosynthesis genes, and 12-oxo-phytodienoic acid reductase were identified near SNPs that had significant associations with different SA traits. In this study, flowering time-related genes were also identified as a positive control for the methods. The total phenotypic variation explained by significant SNPs across SA-scored traits, reflectance data, and flowering time ranged from 6 to 61%, while the heritability value ranged from 4 to 69%. This study identified three new sources of resistant lines to sorghum aphid. These results supported the existing literature, and also revealed several new loci. Markers identified in this study will support marker-assisted breeding for sorghum aphid resistance.

TAT-HSP27 Peptide Improves Neurologic Deficits via Reducing Apoptosis After Experimental Subarachnoid Hemorrhage.

Cell apoptosis plays an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Heat shock protein 27 (HSP27), a member of the small heat shock protein (HSP) family, is induced by various stress factors and exerts protective role on cells. However, the role of HSP27 in brain injury after SAH needs to be further clarified. Here, we reported that HSP27 level of cerebrospinal fluid (CSF) is increased obviously at day 1 in patients with aneurysmal SAH (aSAH) and related to the grades of Hunt and Hess (HH), World Federation of Neurological Surgeons (WFNS), and Fisher score. In rat SAH model, HSP27 of CSF is first increased and then obviously declined; overexpression of HSP27, not knockdown of HSP27, attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex; and overexpression of HSP27 effectively suppresses SAH-elevated activation of mitogen-activated protein Kinase Kinase 4 (MKK4), the c-Jun N-terminal kinase (JNK), c-Jun, and caspase-3. In an in vitro hemolysate-damaged cortical neuron model, HSP2765-90 peptide effectively inhibits hemolysate-induced neuron death. Furthermore, TAT-HSP2765-90 peptide, a fusion peptide consisting of trans-activating regulatory protein (TAT) of HIV and HSP2765-90 peptide, effectively attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex of rats. Altogether, our results suggest that TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis.

Genome-wide association study reveals the genetic architecture of 27 agronomic traits in tomato.

Tomato (Solanum lycopersicum) is a highly valuable fruit crop, and yield is one of the most important agronomic traits. However, the genetic architecture underlying tomato yield-related traits has not been fully addressed. Based on ∼4.4 million single nucleotide polymorphisms obtained from 605 diverse accessions, we performed a comprehensive genome-wide association study for 27 agronomic traits in tomato. A total of 239 significant associations corresponding to 129 loci, harboring many previously reported and additional genes related to vegetative and reproductive development, were identified, and these loci explained an average of ∼8.8% of the phenotypic variance. A total of 51 loci associated with 25 traits have been under selection during tomato domestication and improvement. Furthermore, a candidate gene, Sl-ACTIVATED MALATE TRANSPORTER15, that encodes an aluminum-activated malate transporter was functionally characterized and shown to act as a pivotal regulator of leaf stomata formation, thereby affecting photosynthesis and drought resistance. This study provides valuable information for tomato genetic research and breeding.

SlBBX20 interacts with the COP9 signalosome subunit SlCSN5-2 to regulate anthocyanin biosynthesis by activating SlDFR expression in tomato.

Anthocyanins play vital roles in plant stress tolerance and growth regulation. Previously, we reported that the photomorphogenesis-related transcription factor SlBBX20 regulates anthocyanin accumulation in tomato. However, the underlying mechanism remains unclear. Here, we showed that SlBBX20 promotes anthocyanin biosynthesis by binding the promoter of the anthocyanin biosynthesis gene SlDFR, suggesting that SlBBX20 directly activates anthocyanin biosynthesis genes. Furthermore, we found by yeast two-hybrid screening that SlBBX20 interacts with the COP9 signalosome subunit SlCSN5-2, and the interaction was confirmed by bimolecular fluorescence complementation and coimmunoprecipitation assays. SlCSN5 gene silencing led to anthocyanin hyperaccumulation in the transgenic tomato calli and shoots, and SlCSN5-2 overexpression decreased anthocyanin accumulation, suggesting thSlCSN5-2 enhanced the ubiquitination of SlBBX20 and promoted the degradation of SlBBX20 in vivo. Consistently, silencing the SlCSN5-2 homolog in tobacco significantly increased the accumulation of the SlBBX20 protein. Since SlBBX20 is a vital regulator of photomorphogenesis, the SlBBX20-SlCSN5-2 module may represent a novel regulatory pathway in light-induced anthocyanin biosynthesis.

MAPK11 regulates seed germination and ABA signaling in tomato by phosphorylating SnRKs.

Seed germination is a critical stage in the plant life cycle and it plays an important role in the efficiency of agricultural production. However, our knowledge of the mechanisms that regulate seed germination remains limited. In this study, we identified a novel gene, MAPK11, that encodes mitogen-activated protein kinase 11; its expression was significantly higher in seeds of tomato varieties with a low optimum germination temperature than in those with a high optimum germination temperature. In tests at 25 °C, overexpression of MAPK11 in an accession with optimum germination at 25 °C resulted in a decrease in germination, whereas RNAi of MAPK11 in an accession with optimum germination at 15 °C resulted in increased germination. Furthermore, we found that lines overexpressing MAPK11 exhibited hypersensitivity to ABA during germination. These observations were at least partially explained by the fact that MAPK11 up-regulated both NCED1 expression and ABA biosynthesis, and that it also affected ABA signaling and negatively regulated germination by influencing the phosphorylation of SnRK2.2 in vivo. In addition, we found that MAPK11 interacts with and phosphorylates SnRK1 in vivo, thereby potentially inhibiting its activation. SnRK1 interacted with ABI5 and suppressed the transcription of ABI5, thereby affecting ABA signaling and the regulation of germination. Our results demonstrate that ABA signaling in tomato is affected by a mechanism that depends on MAPK11 phosphorylating SnRKs, and this ultimately influences seed germination.

The novel Nrf2 activator CDDO-EA attenuates cerebral ischemic injury by promoting microglia/macrophage polarization toward M2 phenotype in mice.

The aim of present study was to explore whether 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid (CDDO)-ethylamide (CDDO-EA) attenuates cerebral ischemic injury and its possible mechanisms using a middle cerebral artery occlusion (MCAO) model in C57BL/6 mice. Our results showed that intraperitoneal injection (i.p.) of CDDO-EA (2 and 4 mg/kg) augmented NFE2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in ischemic cortex after MCAO. Moreover, CDDO-EA (2 mg/kg, i.p.) significantly enhanced Nrf2 nuclear accumulation, associated with increased cytosolic HO-1 expression, reduced neurological deficit and infarct volume as well as neural apoptosis, and shifted polarization of microglia/macrophages toward an antiinflammatory M2 phenotype in ischemic cortex after MCAO. Using an in vitro model, we confirmed that CDDO-EA (100 µg/mL) increased HO-1 expression and primed microglial polarization toward M2 phenotype under inflammatory stimulation in BV2 microglial cells. These findings suggest that a novel Nrf2 activator CDDO-EA confers neuroprotection against ischemic injury.

NDW, encoding a receptor-like protein kinase, regulates plant growth, cold tolerance and susceptibility to Botrytis cinerea in tomato.

Plants utilize different mechanisms to respond and adapt to continuously changing environmental factors. Receptor-like protein kinases (RLKs) comprise one of the largest families of plant transmembrane signaling proteins, which play critical and diverse roles in plant growth, development, and stress response. Here, we identified the necrotic dwarf (ndw) mutant introgression line (IL) 6-2, which demonstrated stunting, leaf curl, and progressive necrosis at low temperatures. Based on map-based cloning and transgenic analysis, we determined that the phenotype of ndw mutant is caused by decreased expression of NDW, which encodes an RLK. NDW is a plasma membrane and cytoplasmic located protein. Overexpression of NDW can restore both of the semi-dwarf and necrotic phenotype in IL6-2 at low temperatures, further we found that NDW could significantly reduce susceptibility to Botrytis cinerea. On the contrary, knockdown NDW in M82 plants could increase the sensitivity to B. cinerea. Furthermore, transcriptional expression analysis showed that NDW affects the expression of genes related to the abscisic acid (ABA) signaling pathway. Taken together, these results indicate that NDW plays an important role in regulating plant growth, cold tolerance and mitigating susceptibility to Botrytis cinerea.

The HD-Zip IV transcription factor SlHDZIV8 controls multicellular trichome morphology by regulating the expression of Hairless-2.

Trichomes are specialized epidermal appendages that serve as excellent models to study cell morphogenesis. Although the molecular mechanism underlying trichome morphogenesis in Arabidopsis has been well characterized, most of the regulators essential for multicellular trichome morphology remain unknown in tomato. In this study, we determined that the recessive hairless-2 (hl-2) mutation in tomato causes severe distortion of all trichome types, along with increased stem fragility. Using map-based cloning, we found that the hl-2 phenotype was associated with a 100 bp insertion in the coding region of Nck-associated protein 1, a component of the SCAR/WAVE complex. Direct protein-protein interaction was detected between Hl-2 and Hl (SRA1, specifically Rac1-associated protein) using yeast two-hybrid and co-immunoprecipitation assays, suggesting that these proteins may work together during trichome formation. In addition, knock-down of a HD-Zip IV transcription factor, HDZIPIV8, distorted trichomes similar to the hl-2 mutant. HDZIPIV8 regulates the expression of Hl-2 by binding to the L1-box in the Hl-2 promoter region, and is involved in organizing actin filaments. The brittleness of hl-2 stems was found to result from decreased cellulose content. Taken together, these findings suggest that the Hl-2 gene plays an important role in controlling multicellular trichome morphogenesis and mechanical properties of stems in tomato plants.

Retraction notice to "A SERS-based lateral flow assay biosensor for quantitative and ultrasensitive detection of interleukin-6 in unprocessed whole blood" [Biosens. Bioelectron. 141 (2019) 111432].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the co-Editors in Chief and with the agreement of the authors, after a reader observed that Figure 3b had been partially duplicated with Figure 3a published in a previous publication by the same authors (Anal. Chem. (2017) 89:1163-1169) https://doi.org/10.1021/acs.analchem.6b03536.

The chaperonin 60 protein SlCpn60α1 modulates photosynthesis and photorespiration in tomato.

Photosynthesis, an indispensable biological process of plants, produces organic substances for plant growth, during which photorespiration occurs to oxidize carbohydrates to achieve homeostasis. Although the molecular mechanism underlying photosynthesis and photorespiration has been widely explored, the crosstalk between the two processes remains largely unknown. In this study, we isolated and characterized a T-DNA insertion mutant of tomato (Solanum lycopersicum) named yellow leaf (yl) with yellowish leaves, retarded growth, and chloroplast collapse that hampered both photosynthesis and photorespiration. Genetic and expression analyses demonstrated that the phenotype of yl was caused by a loss-of-function mutation resulting from a single-copy T-DNA insertion in chaperonin 60α1 (SlCPN60α1). SlCPN60α1 showed high expression levels in leaves and was located in both chloroplasts and mitochondria. Silencing of SlCPN60α1using virus-induced gene silencing and RNA interference mimicked the phenotype of yl. Results of two-dimensional electrophoresis and yeast two-hybrid assays suggest that SlCPN60α1 potentially interacts with proteins that are involved in chlorophyll synthesis, photosynthetic electron transport, and the Calvin cycle, and further affect photosynthesis. Moreover, SlCPN60α1 directly interacted with serine hydroxymethyltransferase (SlSHMT1) in mitochondria, thereby regulating photorespiration in tomato. This study outlines the importance of SlCPN60α1 for both photosynthesis and photorespiration, and provides molecular insights towards plant genetic improvement.

Anxiety and related factors in frontline clinical nurses fighting COVID-19 in Wuhan.

The aim of this study was to examine the anxiety status of the frontline clinical nurses in the designated hospitals for the treatment of coronavirus disease 2019 (COVID-19) in Wuhan and to analyze the influencing factors, to provide data for psychologic nursing.This study used a cross-sectional survey design and convenience sampling. The questionnaires were completed by 176 frontline clinical nurses. Anxiety was determined using the Hamilton anxiety scale. General data were collected using a survey. Correlation analyses were used.Among the 176 frontline nurses, 77.3% (136/176) had anxiety. The anxiety scores of the frontline clinical nurse fighting COVID-19 were 17.1 ±â€Š8.1. Anxiety symptoms, mild to moderate anxiety symptoms, and severe anxiety symptoms were found in 27.3%, 25%, and 25% of the nurses, respectively. Sex, age, marital status, length of service, and clinical working time against COVID-19 were associated with anxiety (P < .05).The frontline nurses working in the designated hospitals for the treatment of COVID-19 in Wuhan had serious anxiety. Sex, age, length of service, and clinical working time against COVID-19 were associated with anxiety in those nurses. Psychologic care guidance, counseling, and social support should be provided to the nurses to reduce their physical and mental burden. Nursing human resources in each province should be adjusted according to each province's reality.

Negative Allosteric Modulator of mGluR1 Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) causes permanent neurological sequelae, but the underlying mechanism needs to be further clarified. Here, we show that inhibition of metabotropic glutamate receptor 1 (mGluR1) with negative allosteric modulator JNJ16259685 improves long-term neurobehavioral outcomes in an endovascular perforation model of SAH. JNJ16259685 improves cerebrovascular dysfunction through attenuation of cerebral blood flow (CBF) reduction, cerebral vasoconstrictio, and microthrombosis formation in a rat SAH model. Moreover, JNJ16259685 reduces experimental SAH-induced long-term neuronal damage through alleviation of neuronal death and degeneration. Mechanically, JNJ16259685 maintains phosphorylation of endothelial NO synthase (eNOS) and vasodilator-stimulated phosphoprotein (VASP) and decreases apoptosis-related factors Bax, active caspase-9, and active caspase-3 following experimental SAH. Altogether, our results suggest JNJ16259685 improves long-term functional impairment through neurovascular protection.