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Noncoding RNAs (ncRNAs) regulation of various diseases including cancer has been extensively studied. Reactive oxidative species (ROS) elevated by oxidative stress are associated with cancer progression and drug resistance, while autophagy serves as an ROS scavenger in cancer cells. However, the regulatory effects of ncRNAs on autophagy and ROS in various cancer cells remains complex. Here, we explore how currently investigated ncRNAs, mainly miRNAs and lncRNAs, are involved in ROS production through modulating antioxidant genes. The regulatory effects of miRNAs and lncRNAs on autophagy-related (ATG) proteins to control autophagy activity in cancer cells are discussed. Moreover, differential expression of ncRNAs in tumor and normal tissues of cancer patients are further analyzed using The Cancer Genome Atlas (TCGA) database. This review hypothesizes links between ATG genes- or antioxidant genes-modulated ncRNAs and ROS production, which might result in tumorigenesis, malignancy, and cancer recurrence. A better understanding of the regulation of ROS and autophagy by ncRNAs might advance the use of ncRNAs as diagnostic and prognostic markers as well as therapeutic targets in cancer therapy.

Combining morphological comparison with karyotyping can make a more accurate and comprehensive study of mandarin fish (Siniperca spp.) and hybrid progenies. In recent years, the domestication of hybrid mandarin fish has become a hot spot in China, and it is essential to evaluate the nutritional value of the fish after food conversion. In this study, the F1 hybrid (S. chuatsi ♀ × S. scherzeri♂) were fed with artificial feed for five months. Afterwards, we studied the morphology, karyotypes, and biochemical composition of muscle in the F1 hybrid and its parents. The morphological results showed that total length and body height of the F1 hybrid appear to derive more from S. chuatsi than S. scherzeri. The DNA ploidy and karyotype results indicated that the F1 hybrid have a diploid chromosome number (2n = 48) and the same karyotypes (2n = 4sm + 14th+30t, NF = 52) with its parents, suggesting that the chromosome of the mandarin fish has convergence in the process of evolution. The results of biochemical composition of muscle showed that there were no significant difference in other nutritional indicators (P > 0.05), except the Gly (glycine) content of the F1 hybrid was significantly higher than that of S. chuatsi (P

Background Depression is a common psychiatric disorder associated with the defects in GABAergic neurotransmission. α-Dystroglycan (α-DG), a cell adhesion molecule known to be essential for skeletal muscle integrity, is also present at inhibitory synapses in the central nervous system and forms a structural element in certain synapses. However, the role of α-DG in the regulation of depressive-like behaviors remains largely unknown. Methods Depressive-like behaviors were induced by chronic social defeat stress (CSDS). Surface protein was extracted by a biotin kit and the expression of protein was detected by western blotting. Intra-hippocampal microinjection of the lentivirus or adeno-associated virus or agrin intervention were carried out using a stereotaxic instrument and followed by behavioral tests. The miniature inhibitory postsynaptic currents (mIPSCs) were recorded by whole-cell patch-clamp techniques. Results The expression of α-DG and glycosylated-α-DG (GLY-α-DG) in the ventral hippocampus (vHip) was significantly lower in CSDS susceptible male mice than that in controls, accompanied with a decreased surface expression of GABAAR γ2 and reduced GABAergic neurotransmission. RNAi-mediated knockdown of dystroglycan encoding gene dystroglycan 1 (DAG1) increased the susceptibility of mice to sub-threshold stress. Both in vivo administration of agrin and overexpression of like-acetylglucosaminyltransferase (LARGE) ameliorated depressive-like behaviors and restored the decrease in surface expression of GABAAR γ2 and the amplitude of mIPSCs in CSDS-treated mice. Conclusions Our findings demonstrate that GLY-α-DG plays a role in the pathophysiological process of depressive-like behaviors by regulating the surface expression of GABAAR γ2 and the GABAergic neurotransmission in the vHip.

In this study, we investigated the changes in global methylation status and its functional relevance in childhood atopic dermatitis (AD). Differences in epigenome-scale methylation events in peripheral blood associated with childhood AD were screened using DNA methylation arrays of 24 patients with AD compared with 24 control subjects. Of the 16,840 differentially methylated CpG regions between AD and control subjects, >97% CpG loci revealed hypomethylation in patients with childhood AD. Among the globally hypomethylated loci, we identified two CpG clusters within the golli-mbp locus of the MBP gene, which was functionally enriched by subnetwork enrichment analysis as an orchestrator among associated genes. The differential hypomethylation of the top-ranked cg24700313 cluster in the golli-mbp locus was validated by pyrosequencing in an independent cohort of 224 children with AD and 44 control subjects. DNA methylation was found to be negatively correlated with disease severity but showed no significant correlation with IgE levels after age adjustment. The multivariate correlation analysis represents a higher score in AD intensity with significantly increased IgE levels and decreased methylation levels in cg27400313. We concluded that methylation loss in the golli-mbp locus is an epigenetic factor associated with disease severity of childhood AD.

Antimicrobial-resistant pathogens in the environment and wastewater treatment systems, many of which are also important pollutant degraders and are difficult to control by traditional disinfection approaches, have become an unprecedented treat to ecological security and human health. Here, we propose the adoption of genetic editing techniques as a highly targeted, efficient and simple tool to control the risks of environmental pathogens at the source. An 'all-in-one' plasmid system was constructed in Aeromonas hydrophila to accurately identify and selectively inactivate multiple key virulence factor genes and antibiotic resistance genes via base editing, enabling significantly suppressed bacterial virulence and resistance without impairing their normal phenotype and pollutant-degradation functions. Its safe application for bioaugmented treatment of synthetic textile wastewater was also demonstrated. This genetic-editing technique may offer a promising solution to control the health risks of environmental microorganisms via targeted gene inactivation, thereby facilitating safer application of water treatment biotechnologies.

Acute ischemic stroke is a challenging disease that threatens the life of older people. Dysfunction of brain endothelial cells is reported to be involved in the pathogenesis of acute ischemic stroke. Ramelteon is a novel agonist of melatonin receptor developed for the treatment of insomnia. Recently, the promising protective effect of Ramelteon on brain injury has been widely reported. The present study aims to investigate the protective effect of Ramelteon against free fatty acid (FFA)-induced damages in brain vascular endothelial cells and the underlying mechanism. Firstly, we discovered that Ramelteon administration remarkably reversed the decreased cell viability, increased LDH release, activated oxidative stress, and excessive released inflammatory factors caused by FFAs. Secondly, Ramelteon extensively suppressed the attachment of U937 monocytes to bEnd.3 brain endothelial cells induced by FFAs. In addition, the elevated expression of E-selectin and the reduced expression of KLF2 induced by FFAs were pronouncedly alleviated by Ramelteon. Lastly, silencing of KLF2 abolished the protective effects of Ramelteon against FFA-induced expression of E-selectin and the attachment of U937 monocytes to bEnd.3 brain endothelial cells. In conclusion, Ramelteon mitigated FFA-induced attachment of monocytes to brain vascular endothelial cells by increasing the expression of KLF2 and reducing the expression of E-selectin.

Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a secretory serine protease that plays multiple biological functions in the regulation of physiological and pathological processes. PCSK9 inhibitors decrease the circulating LDL-cholesterol level with well-known preventive and therapeutic effects on atherosclerosis (AS). Still, increasing evidence shows that the direct impact of PCSK9 on the vascular wall also plays an important role in atherosclerotic progression. Compared with other vascular cells, a large proportion of PCSK9 is originated from vascular smooth muscle cells (VSMC). Therefore, defining the effect of VSMC-derived PCSK9 on response changes, such as phenotypic switch, apoptosis, autophagy, inflammation, foam cell formation, and calcification of VSMC, helps us better understand the “pleiotropic” effects of VSMC on the atherosclerotic process. In addition, our understanding of the mechanisms of PCSK9 controlling VSMC functions in vivo is far from enough. This review aims to holistically evaluate and analyze the current state of our knowledge regarding PCSK9 actions affecting VSMC functions and its mechanism in atherosclerotic lesion development. A mechanistic understanding of PCSK9 effects on VSMC will further underpin the success of a new therapeutic strategy targeting AS.

Background Panax notoginseng is a highly valued medicinal herb used widely in China and many Asian countries. Its root and rhizome have long been used for the treatment of cardiovascular and hematological diseases. Imaging the spatial distributions and dynamics of metabolites in heterogeneous plant tissues is significant for characterizing the metabolic networks of Panax notoginseng, and this will also provide a highly informative approach to understand the complex molecular changes in the processing of Panax notoginseng. Methods Here, a high-sensitive MALDI-MS imaging method was developed and adopted to visualize the spatial distributions and spatiotemporal changes of metabolites in different botanical parts of Panax notoginseng. Results A wide spectrum of metabolites including notoginsenosides, ginsenosides, amino acids, dencichine, gluconic acid, and low-molecular-weight organic acids were imaged in Panax notoginseng rhizome and root tissues for the first time. Moreover, the spatiotemporal alterations of metabolites during the steaming of Panax notoginseng root were also characterized in this study. And, a series of metabolites such as dencichine, arginine and glutamine that changed with the steaming of Panax notoginseng were successfully screened out and imaged. Conclusion These spatially-resolved metabolite data not only enhance our understanding of the Panax notoginseng metabolic networks, but also provide direct evidence that a serious of metabolic alterations occurred during the steaming of Panax notoginseng.

Male infertility may be caused by genetic and/or environmental factors that impair spermatogenesis and sperm maturation. High-altitude (HA) hypoxic environments represent one of the most serious challenges faced by humans that reside in these areas. To assess the influence of the plateau environment on semen parameters, 2,798 males, including 1,111 native Tibetans and 1,687 Han Chinese individuals living in the plains (HCILP) who underwent pre-pregnancy checkups, were enrolled in this study. The semen samples of males were evaluated to determine conventional sperm parameters, sperm morphology, and sperm movement. Reproductive endocrine hormones (REHs) were detected in 474 males, including 221 Tibetans and 253 HCILP. Due to recurrent abortions in partners, the DNA fragmentation index (DFI) of 133 native Tibetans and 393 HCILP individuals was further compared. Luteinizing hormone (LH) (4.94 ± 2.12 vs. 3.29 ± 1.43 U/L), prolactin (11.34 ± 3.87 vs. 8.97 ± 3.48 nmol/L), E2/T (0.22 ± 0.11 vs 0.11 ± 0.05), median total sperm motility (61.20% vs. 51.56%), and DFI (23.11% vs. 7.22%) were higher in males from plateau areas while median progressive motility (PR) (35.60% vs. 41.12%), total number of PR sperms (51.61 vs. 59.63 mil/ejaculate), percentage of normal form sperms (3.70% vs. 6.00%), curvilinear velocity (36.10 vs. 48.97 μm/s), straight-line (rectilinear) velocity (14.70 vs. 31.52 μm/s), estradiol (103.82 ± 45.92 vs. 146.01 ± 39.73 pmol/L), progesterone (0.29 ± 0.27 vs. 2.22 ± 0.84 nmol/L), testosterone (4.90 ± 1.96 vs. 14.36 ± 5.24 nmol/L), and testosterone secretion index (ratio of testosterone to LH) (33.45 ± 22.86 vs 145.78 ± 73.41) were lower than those in males from the plains. There was no difference in median total sperm number (157.76 vs. 151.65 mil/mL), sperm concentration (52.40 vs. 51.79 mil/mL), volume (3.10 vs. 3.10 mL), total normal form sperms (5.91 vs. 6.58 mil/ejaculate, p50), and follicle-stimulating hormone (FSH) levels (4.13 ± 2.55 U/L vs 3.82 ± 2.35 U/L) between the two groups of males. The REH and sperm parameters of males from HA hypoxic environments were adaptively altered. Although the total number of PR sperm decreased and DFI increased, the Tibetan population that lives at HAs has been found to grown continuously and rapidly. These results supplement prior findings regarding the impact of HA on male reproductive function.

The accurate taxonomic concept of the fungal Chaetomium species has been a hard work due to morphological similarity. Chemotaxonomy based on secondary metabolites is a powerful tool for taxonomical purposes, which could be used as an auxiliary reference to solve the problems encountered in the classification of Chaetomium. Among secondary metabolites produced by Chaetomium, cytochalasans and azaphilones exhibited a pattern of distribution and frequency of occurrence that establish them as chemotaxonomic markers for the Chaetomium species. This review attempted to elucidate the composition of the Chaetomium species and its relationship with classical taxonomy by summarizing the pattern of cytochalasans and azaphilones distribution and biosynthesis in the Chaetomium species. KEY POINTS: • Secondary metabolites from the genus Chaetomium are summarized. • Cytochalasans and azaphilones could be characteristic metabolites of the Chaetomium species. • Cytochalasans and azaphilones could be used to analyze for taxonomical purposes.

Southern East Asia, including Guangxi and Fujian provinces in China, is home to diverse ethnic groups, languages, and cultures. Previous studies suggest a high complexity regarding population dynamics and the history of southern East Asians. However, large-scale genetic studies on ancient populations in this region are hindered by limited sample preservation. Here, using highly efficient DNA capture techniques, we obtain 48 complete mitochondrial genomes of individuals from Guangxi and Fujian in China and reconstruct their maternal genetic history over the past 12,000 years. We find a strong connection between southern East Asians dating to ~12,000-6000 years ago and present-day Southeast Asians. In addition, stronger genetic affinities to northern East Asians are observed in historical southern East Asians than Neolithic southern East Asians, suggesting increased interactions between northern and southern East Asians over time. Overall, we reveal dynamic connections between ancient southern East Asians and populations located in surrounding regions, as well as a shift in maternal genetic structure within the populations over time.

The cyclic GMP‒AMP synthase (cGAS)‒stimulator of interferon genes (STING) signaling pathway senses the presence of cytosolic DNA and, in turn, triggers downstream signaling to induce the expression of inflammatory and type I interferon genes in immune cells. Whereas the innate immune function of the cGAS‒STING pathway is well studied over the past years, emerging evidence suggests that this signaling pathway may have additional functions beyond innate immune surveillance. Consistent with this notion, dysregulation of the cGAS‒STING signaling pathway in adipocytes, hepatocytes, and renal proximal tubule epithelial cells are associated with metabolic dysfunction, impaired energy homeostasis, and kidney diseases. In this review, we summarize current understanding of the cGAS‒STING pathway in several metabolic diseases such as obesity, insulin resistance, alcoholic and nonalcoholic fatty liver diseases, as well as acute kidney injury and chronic kidney disease. We also review the interaction between the cGAS‒STING pathway and lipid metabolism. Lastly, we discuss potential mechanisms by which cGAS‒STING signaling regulates metabolism and point toward future avenues of research targeting the cGAS‒STING pathway as possible means to treat common metabolic disorders.

The direct visualization of vaccine fate is important to investigate its immunoactivation process to elucidate the detailed molecular reaction process at single‐molecular level. Yet, visualization of the spatiotemporal trafficking of vaccines remains poorly explored. Here, we show that quantum dot (QD) nanomaterials allow for monitoring vaccine dynamics and for amplified immune response. Synthetic QDs enable efficient conjugation of antigen and adjuvants to target tissues and cells, and non‐invasive imaging the trafficking dynamics to lymph nodes and cellular compartments. The nanoparticle vaccine elicits potent immune responses and anti‐tumor efficacy alone or in combination with programmed cell death protein 1 blockade. The synthetic QDs showed high fluorescence quantum yield and superior photostability, and the reliable and long‐term spatiotemporal tracking of vaccine dynamics was realized for the first time by using the synthetic QDs, providing a powerful strategy for studying immune response and evaluating vaccine efficacy., Visualization of spatiotemporal trafficking of vaccines is achieved with synthetic QDs for potent immune activation.

Corynespora cassiicola, which causes Corynespora leaf spot, results in considerable yield loss of cucumber grown in greenhouses. Frequent reports of reduced efficacy and control failure of fungicides warrant new, efficient alternative chemistries. In this study, the sensitivity of C. cassiicola to benzovindiflupyr was evaluated using a collection of 81 isolates collected from Shandong, China. The mean EC50 values for mycelial growth, spore germination, and germ tube elongation of C. cassiicola were 0.69 ± 0.44, 0.12 ± 0.063, and 0.13 ± 0.076 µg ml−1, respectively. Benzovindiflupyr treatment led to a reduced respiration rate and ATP production of C. cassiicola and decreased spore pathogenicity by 21.9% on average. Additionally, detached cucumber leaves sprayed with fungicides before or after inoculation were used to assess the efficacy of benzovindiflupyr against C. cassiicola. Benzovindiflupyr (150 µg ml−1) exhibited preventive and curative efficacies of 86.9 and 77.1%, respectively. Benzovindiflupyr at 150 g a.i. ha−1 provided over 70% efficacy in field trials performed in 2018 and 2019, which was significantly higher than that of the reference fungicides fluopyram and fluxapyroxad at the same dose. Furthermore, the yield of commercial cucumber increased as disease incidence decreased. Our findings pave the way for the introduction of benzovindiflupyr in the integrated management of Corynespora leaf spot.

The design of three novel fatty nitrogen mustard-based anticancer agents with fluorophores incorporated into the alkene structure (CXL 118, CXL121, and CXL122) is described in this report. The results indicated that these compounds are selectively located in lysosomes and exhibit effective antitumour activity. Notably, these compounds can directly serve as both reporting and imaging agents in vitro and in vivo without the need to add other fluorescent tagging agents.

Genes containing GTP_EFTU domain mainly express elongation factors (EF), Small GTPases, and GTP-binding proteins, which are closely related to protein synthesis, extension and ATP synthesis. In this study, we identified 39 genes containing GTP_EFTU domains from peppers. The evolutionary trees constructed from capsicum, Arabidopsis, rice, and tomato are mainly divided into 7 subfamilies. Using PacBio (Pacific Biosciences) sequencing and assembly data, we extracted these 39 gene sequences, from which 25 genes had alternative splicing. Particularly, the Capana08g000545 had 16 alternative splicing processes. Accordingly, we performed promoter sequence analysis, subcellular location prediction, the expression analysis of different tissues and periods, and also the GO (Gene ontology) analysis of co-expressed genes. Lastly we did the qRT-PCR analysis in 5 stages of pepper fruit development. These analyses revealed important structural and functional information for the identified 39 genes that contain GTP_EFTU domains, providing important references for further follow-up experiments to verify the genes function on plants or their unique roles in peppers.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor without curable therapy. Surgical resection remains the first choice of patients with GBM but tumors relapse rapidly even combined with conventional chemoradiotherapy. The mechanism of GBM rapid recurrence is poorly understood, which is largely due to the lack of an appropriate animal model, thus heavily impedes the improvement of postoperative therapy. Here we established a highly reproducible mouse GBM surgical model by using the syngeneic G422TN-GBM cells, which faithfully recapitulates the features of rapid recurrence of human GBM after surgery. Implanting 2 × 103–5 × 104 of G422TN-GBM cells in mouse cerebral cortex caused death in all animal within 23 days, while surgery was an effective therapy but not curable. After complete removal of visible tumors on day 5–9 of tumor growth, the tumors recurred macroscopically within 5 days accompanied by increasing infiltrative cancer foci. Mechanistically, the rapid recurrence of resected tumors was positively correlated to early Akt activation, which subsequently upregulated PD-L1/Vimentin and promoted proliferation/migration of cancer cells. In addition, environmental astrocytic activation with strong PD-L1 signal was prominent. Taken together, we provided a novel GBM surgical recurrence model for preclinical studies and suggested complicated recurring mechanisms involving in strong oncogenic signaling as well as immune inhibitory signals from both GBM cells and their neighboring astrocytes.

Background:. Age-related macular degeneration (AMD) is the leading cause of vision loss worldwide. However, the mechanisms involved in the development and progression of AMD are poorly delineated. We aimed to explore the critical genes involved in the progression of AMD. Methods:. The differentially expressed genes (DEGs) in AMD retinal pigment epithelial (RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564, which were downloaded from the gene expression omnibus database. The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The hub genes were identified from these DEGs through protein-protein interaction network analyses. The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866. Following the identification of AMD-related key genes, the potential small molecule compounds targeting the key genes were predicted by PharmacoDB. Finally, a microRNA-gene interaction network was constructed. Results:. Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples. These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication, cell cycle, and proteasome-mediated protein polyubiquitination. Among the top ten hub genes, HSP90AA1, CHEK1, PSMA4, PSMD4, and PSMD8 were upregulated in the senescent ARPE-19 cells. Additionally, the drugs targeting HSP90AA1, CHEK1, and PSMA4 were identified. We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE. Conclusions:. Based on our findings, HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD. Targeting HSP90AA1, CHEK1, PSMA4, PSMD4, and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence.

Long noncoding RNAs (lncRNAs) are a group of nonprotein coding transcripts that play a critical role in cancer progression. However, the role of lncRNA in metformin-induced inhibition of cell growth and its biological function in gastric cancer remain largely unknown. In this study, we identified an oncogenic lncRNA, Loc100506691, the expression of which was decreased in gastric cancer cells with metformin treatment. Moreover, Loc100506691 was significantly overexpressed in gastric cancer compared with adjacent normal tissues (p < 0.001), and high Loc100506691 expression was significantly correlated with poor survival of patients with gastric cancer. Additionally, Loc100506691 knockdown could significantly suppress gastric cancer cell growth in vitro, and ectopic Loc100506691 expression accelerated tumor growth in an in vivo mouse model. Analysis of the cell cycle revealed that Loc100506691 knockdown induced cell cycle arrest at the G2/M phase by impairing cell entry from the G2/M to G1 phase. Loc100506691 negatively regulated CHAC1 expression by modulating miR-26a-5p/miR-330-5p expression, and CHAC1 knockdown markedly attenuated Loc100506691 knockdown-induced gastric cancer cell growth and motility suppression. We concluded that anti-proliferative effects of metformin in gastric cancer may be partially caused by suppression of the Loc100506691-miR-26a-5p/miR-330-5p-CHAC1 axis., Graphical abstract, This new signaling pathway broadens our understanding of the mechanism and anticancer potential of metformin in the treatment of gastric cancer. Our findings showed anti-proliferative effects of metformin in gastric cancer may be caused by suppression of the novel Loc100506691-CHAC1 axis.

Cereal cyst nematode (Heterodera avenae), an important plant-parasitic nematode causing yield losses of wheat, has been found in many provinces in China. It is urgent to develop an effective method of protecting wheat from H. avenae damage. Because of its novel mode of action, fluopyram has been registered for controlling root-knot nematodes on cucumber and tomato in China. However, the bioactivity of fluopyram against H. avenae and whether this seed treatment can effectively control H. avenae on wheat remains unknown. In this study, a bioactivity assay revealed that fluopyram increased the mortality of H. avenae second-stage juveniles (J2), with lethal concentrations (LC) required to kill 50% (LC50) and 90% (LC90) of 0.92 mg⋅liter−1 and 2.92 mg⋅liter−1, respectively. Hatching tests showed that the H. avenae egg hatching percent was reduced by 35.2 to 69.2% with fluopyram at rates of 1.6 to 6.4 mg⋅liter−1, and that the egg hatching period was delayed by 3 to 9 days compared with the control. During pot and field trials, fluopyram seed treatment significantly reduced the H. avenae population density and increased wheat yield by 3.0 to 13.7%. Therefore, fluopyram seed treatment is an effective approach for the management of H. avenae on wheat in China.

Large-scale green tides in the Yellow Sea occurred for 13 consecutive years since 2007. The unusual co-occurrence of green tides and golden tides occurred in the Yellow Sea in 2017. The causative species are Ulva prolifera and/or Sargassum horneri. Previous studies on physiological response characteristics of U. prolifera and S. horneri are done in the laboratory mainly, and there is no in-situ comparative study in this regard. In this study, the in-situ physiological response characteristics of both species were measured. The results indicated that cyclic electron flow and antioxidant system play more important roles in protecting U. prolifera, while non-photochemical quenching is more important for adapting to the environment in S. horneri. U. prolifera has a stronger ability to utilize nutrients to rapidly increase its biomass under a suitable condition compared to S. horneri.

Microbial fabrication is eco-friendly for nobel-metal catalysts typically used in proton exchange membrane fuel cell (PEMFC). In our study, nano-Pd electrocatalysts were successfully prepared by using three Shewanellas as precursors through hydrogen reduction (200 °C) and carbonization (800 °C). The analysis revealed that the catalysts showed outstanding ORR electrocatalytic performance via a predominant four-electron oxygen reduction pathway in alkaline medium. The best performance was obtained for Pd/HNC-32, which showed a mass activity at 0.526 A mg−1, 3.78 times higher than that of commercial Pd/C. Shewanella putrefaciens CN-32 was a more effective Pd-adsorbent. The enhanced performance can be ascribed to the small Pd-particle size and uniform dispersion on microbial support, which results from stronger hydrophilicity of Shewanella putrefaciens CN-32. The content of nitrogen is another key to the performance of Pd/HNC-32. This study developed a promising strategy for screening microbial strains for electrocatalyst fabrication.

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase, which plays an essential role in both innate and adaptive immunity. However, the key molecular mechanisms that regulate SYK activity are poorly understood. Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation. We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK. This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors (CLRs), and also prevented the interaction with the phosphatase SHP-1. Therefore, deficiency of Trim31 in bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) dampened SYK-mediated signaling and inhibited the secretion of proinflammatory cytokines and chemokines against the fungal pathogen Candida albicans infection. Trim31−/− mice were also more sensitive to C. albicans systemic infection than Trim31+/+ mice and exhibited reduced Th1 and Th17 responses. Overall, our study uncovered the pivotal role of TRIM31-mediated K27-linked polyubiquitination on SYK activation and highlighted the significance of TRIM31 in anti-C. albicans immunity.

Benzothiazole is a microbial volatile compound with strong antifungal activity against the phytopathogenic fungus Botrytis cinerea, but its mode of action against fungi remains largely unknown. Understanding the molecular mechanisms underlying its activity could aid the design and synthesis of similar compounds against pathogenic fungi. Based on the results of morphological and antifungal activity assays, B. cinerea was exposed to 2.5 µl/liter of benzothiazole for 12, 24, and 48 h, and an isobaric tags for relative and absolute quantitation-based quantitative proteomic analysis showed that 378 out of 5,110 identified proteins were differentially expressed proteins (DEPs). The majority of these DEPs were associated with carbohydrate metabolism, oxidation reduction processes, and energy production. Further analysis showed that benzothiazole inhibited mitochondrial membrane organization and decreased the mitochondrial membrane potential of B. cinerea. In addition, the key enzymes of the glyoxylate cycle were downregulated after benzothiazole treatment, and a biochemical analysis indicated that inhibition of the glyoxylate cycle by benzothiazole blocked nutrient availability and interfered with adenosine triphosphate generation. This study provides markers for future research of the molecular responses of B. cinerea to benzothiazole stress.

Retinitis pigmentosa (RP) is a group of inherited photoreceptor degeneration diseases that causes blindness without effective treatment. The pathogenesis of retinal degeneration involves mainly oxidative stress and inflammatory responses. Zeaxanthin dipalmitate (ZD), a wolfberry-derived carotenoid, has anti-inflammatory and anti-oxidative stress effects. Here we investigated whether these properties of ZD can delay the retinal degeneration in rd10 mice, a model of RP, and explored its underlying mechanism. One shot of ZD or control vehicle was intravitreally injected into rd10 mice on postnatal day 16 (P16). Retinal function and structure of rd10 mice were assessed at P25, when rods degenerate substantially, using a visual behavior test, multi-electrode-array recordings and immunostaining. Retinal pathogenic gene expression and regulation of signaling pathways by ZD were explored using transcriptome sequencing and western blotting. Our results showed that ZD treatment improved the visual behavior of rd10 mice and delayed the degeneration of retinal photoreceptors. It also improved the light responses of photoreceptors, bipolar cells and retinal ganglion cells. The expression of genes that are involved in inflammation, apoptosis and oxidative stress were up-regulated in rd10 mice, and were reduced by ZD. ZD further reduced the activation of two key factors, signal transducer and activator of transcription 3 and chemokine (C-C motif) ligand 2, down-regulated the expression of the inflammatory factor GFAP, and inhibited extracellular signal regulated protein kinases and P38, but not the JNK pathways. In conclusion, ZD delays the degeneration of the rd10 retina both morphologically and functionally. Its anti-inflammatory function is mediated primarily through the signal transducer and activator of transcription 3, chemokine (C-C motif) ligand 2 and MAPK pathways. Thus, ZD may serve as a potential clinical candidate to treat RP.

Although Uzbekistan and Central Asia are known for the well-studied Bronze Age civilization of the Bactria–Margiana Archaeological Complex (BMAC), the lesser-known Iron Age was also a dynamic period that resulted in increased interaction and admixture among different cultures from this region. To broaden our understanding of events that impacted the demography and population structure of this region, we generated 27 genome-wide single-nucleotide polymorphism capture data sets of Late Iron Age individuals around the Historical Kushan time period (∼2100–1500 BP) from three sites in South Uzbekistan. Overall, Bronze Age ancestry persists into the Iron Age in Uzbekistan, with no major replacements of populations with Steppe-related ancestry. However, these individuals suggest diverse ancestries related to Iranian farmers, Anatolian farmers, and Steppe herders, with a small amount of West European Hunter Gatherer, East Asian, and South Asian Hunter Gatherer ancestry as well. Genetic affinity toward the Late Bronze Age Steppe herders and a higher Steppe-related ancestry than that found in BMAC populations suggest an increased mobility and interaction of individuals from the Northern Steppe in a Southward direction. In addition, a decrease of Iranian and an increase of Anatolian farmer-like ancestry in Uzbekistan Iron Age individuals were observed compared with the BMAC populations from Uzbekistan. Thus, despite continuity from the Bronze Age, increased admixture played a major role in the shift from the Bronze to the Iron Age in southern Uzbekistan. This mixed ancestry is also observed in other parts of the Steppe and Central Asia, suggesting more widespread admixture among local populations.

Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling. Yet, despite the importance of O-glycans, relatively few tools exist for their analysis and modification. In particular, there is a need for enzymes that can cleave the wide range of O-glycan structures found on protein surfaces, to facilitate glycan profiling and editing. Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide. We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family. Through structural and sequence analysis, we identified active site residues that modulate specificity. Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved. Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells. Access to this enzyme opens up improved methodologies for unraveling the glycan code.

Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HTDRN) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HTDRN to hypothalamic arcuate nucleus (5-HTDRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT2C and 5-HT1B receptors, whereas activation of 5-HTDRN to ventral tegmental area (5-HTDRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HTDRN neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HTDRN neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.

The cosmopolitan phytoplankton species Eucampia zodiacus Ehrenberg 1839 is a common harmful algal bloom (HAB) species with significant negative ecological impact. However, molecular information for this HAB species is limited. In this study, the complete chloroplast genome (cpDNA) of E. zodiacus was constructed for the first time. The circular genome was 118,107 bp in length, containing a pair of inverted repeats (IR) (6991 bp each). The overall GC content of E. zodiacus cpDNA was 31.64%. It encoded 169 genes, including 131 protein-coding genes (PCGs), 30 tRNA genes, one tmRNA gene, one ncRNA gene, and six rRNA genes in IR regions. Phylogenetic analysis using concatenated PCGs of 56 diatom cpDNAs strongly supported that E. zodiacus was closely related to Cerataulina daemon, which belongs to the same family Hemiaulaceae according to AlgaeBase. Syntenic analysis revealed nearly identical gene order between the two cpDNAs, except for an inversion in the small single-copy (SSC) region.

SARS-CoV-2 infection causes a wide spectrum of clinical manifestations in humans, and olfactory dysfunction is one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism by which SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein, we demonstrate that intranasal inoculation with SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not the olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 (hACE2) mice. The sustentacular cells and Bowman’s gland cells in the OE were identified as the major target cells of SARS-CoV-2 before invasion into olfactory sensory neurons (OSNs). Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration and directly impairs the uniformity of the OE structure. Combined transcriptomic and quantitative proteomic analyses revealed the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates olfactory dysfunction in COVID-19 patients and provides critical clues for understanding the physiological basis for extrapulmonary manifestations of COVID-19.

Walnut blight (WB), caused by the bacterium Xanthomonas arboricola pv. juglandis,continues to be a serious disease of walnut in northern China, where weather conditions favor disease development. From 2013 to 2017, WB incidences in walnut cv. ‘Liaoning 1’ were investigated in three areas (Dalian,Suizhong and Jianchang areas) in the Liaoning province, northeastern China. WB incidence was high in Dalian (23.72%) and Suizhong (24.31%) but was low in Jianchang (12.98%). Relative humidity is a key meteorological factor that affected the differences between areas. Ten walnut cultivars were surveyed in 2013, 2015, and 2017 for their susceptibility to blight. Lateral-bearing walnut cultivars showed a higher incidence and were found more susceptible to WB compared with terminal-bearing cultivars. In order to test the most effective chemical spray methods, bactericide screening trials were conducted comprising 12 different types of bactericides and mixtures in 2015. The combination of kasugamycin+mancozeb was most effective in controlling WB incidence resulting in lowest fruit disease incidence (2.63%). Subsequently, minimal spray trials were studied to determine the most effective chemical control as well as timing and frequency of application in 2017. The study confirmed these results of studies done in California: the best timing for the first spray application was at 30%–40% pistillate flower emergence and subsequently spray times were at 6 days and 16 days interval. Results of this study provide essential information to better understand the complexity of this walnut disease toward developing effective control management strategies globally.

Background and objectives Manipulating different signaling pathways via small molecules could efficiently induce cardiomyocytes from human induced pluripotent stem cells (hiPSC). However, the effect of transcription factors on the hiPSC-directed cardiomyocytes differentiation remains unclear. Transcription factor, p53 has been demonstrated indispensable for the early embryonic development and mesendodermal differentiation of embryonic stem cells (ESC). We tested the hypothesis that p53 promotes cardiomyocytes differentiation from human hiPSC. Methods and results Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, we demonstrated that forced expression of p53 in hiPSC remarkably improved the differentiation efficiency of cardiomyocytes from hiPSC, whereas knockdown endogenous p53 decreased the yield of cardiomyocytes. This p53-mediated increased cardiomyocyte differentiation was mediated through WNT3, as evidenced by that overexpression of p53 upregulated the expression of WNT3, and knockdown of p53 decreased the WNT3 expression. Mechanistic analysis showed that the increased cardiomyocyte differentiation partially depended on the amplified mesendodermal specification resulted from p53-mediated activation of WNT3-mediated Wnt signaling. Consistently, endogenous WNT3 knockdown significantly ameliorated mesendodermal specification and subsequent cardiomyocyte differentiation. Conclusions These results provide a novel insight into the potential effect of p53 on the development and differentiation of cardiomyocyte during embryogenesis.

Larimichthys crocea is a marine fish species cultured in China. Short-term starvation is often applied to improve the quality of cultured L. crocea, and the expression of ghrelin in tissues of stomach, muscle, brain, intestines, liver, and kidney, involved in starvation response, under starvation conditions were studied to understand the effect of starvation on the expression of ghrelin in L. crocea juveniles. The ghrelin expression was tissue-specific, and expression was significantly higher in the stomach compared to other tissues (P

BACKGROUND Understanding performance matching of pesticide droplets on the surface of cucumber leaves modified by powdery mildew is of practical importance for the agricultural sector. Here, the surface texture and wettability of cucumber leaves covered by powdery mildew were systematically examined using parameters such as micromorphology, physicochemical properties, and liquid droplet contact angle measurements. RESULTS Our results show that powdery mildew growth can be divided into four distinct stages according to the surface texture characteristics of the diseased cucumber leaves. The three-dimensional (3D) surface structures of powdery mildew layers on cucumber leaves had individual characteristics at different mildew growth stages, among which powdery mildew was more easily spread in the last growth stage, and powdery mildew height was greatest in the NO. 2 growth stage (Sa = 425.35 μm). Surface free energy values, static contact angle, and contact angle hysteresis all correlated strongly with the surface characteristics of powdery mildew layers at different growth stages. When the concentration of surfactant reached the critical micelle concentration, the wetting state of AEO-5 solution droplets on the surface of cucumber powdery mildew leaves reached the Wenzel state more easily. The wettability of a droplet on the leaf surface depends on the state of the monomer and micelle in the surfactant solution and the surface characteristics of the powdery mildew-covered leaf. CONCLUSION The 3D structure and relative dielectric constant of powdery mildew-covered leaves influenced surface texture characteristics, which in turn controlled the wetting and matching ability of surfactant droplets on diseased leaves. This work provides valuable new insights into the matching of the structure of powdery mildew-covered plant leaves with the properties of surfactant solutions. © 2021 Society of Chemical Industry.

Cancer-associated fibroblasts (CAFs) can promote the development and metastasis of prostate cancer partly by mediating tumor-associated inflammation. An increasing amount of studies have focused on the functional interactions between CAFs and immune cells in the tumor microenvironment (TME). We previously reported that G protein-coupled receptor 30 (GPR30) was highly expressed in prostate CAFs and plays a crucial role in prostate stromal cell activation. However, the effect and underlying mechanism of GPR30 expression in prostate CAFs affecting the interaction between CAFs and tumor-associated macrophages (TAMs) need further elucidation. Here, we found that, compared with CAF-shControl, CAF-shGPR30 inhibited macrophage migration through transwell migration assays, which should be attributed to the decreased expression of C-X-C motif chemokine ligand 12 (CXCL12). In addition, macrophages treated with a culture medium of CAF-shGPR30 exhibited attenuated M2 polarization with downregulated M2-like markers expression. Moreover, macrophages stimulated with a culture medium of CAF-shGPR30 were less efficient in promoting activation of fibroblast cells and invasion of PCa cells. Finally, cocultured CAF-shGPR30 and macrophages suppressed PCa cell invasion compared to cocultured CAF-shControl and macrophages by decreasing interleukin-6 (IL-6) secretion, and this effect could be abrogated with rescue expression of IL-6. Our results pinpoint the function of GPR30 in prostate CAFs on regulating the CAF-TAM interaction in the TME and provide new insights into PCa therapies via regulating TME.

The prevalence and destructiveness of anthracnose, caused by Colletotrichum scovillei, in pepper production regions seriously affects pepper yield and quality. Mefentrifluconazole, the first of the isopropanol-azole subgroup of triazole fungicides, was introduced for the control of pepper anthracnose. However, the growth characteristics of pepper fruit and rapid spread of anthracnose suggest that the fungicide application method must be optimized to enhance fungicide efficacy. The sensitivity of C. scovillei to mefentrifluconazole was determined by mycelial growth and germ tube elongation assays using 157 single-spore isolates with mean 50% effective concentration values of 0.462 ± 0.138 and 0.359 ± 0.263 mg/liter, respectively. The in vivo data also showed that mefentrifluconazole had favorable protective and curative effects against pepper anthracnose. Mefentrifluconazole significantly affected C. scovillei infection on pepper by reducing appressorium formation and sporulation, shriveling spores and germ tubes, and causing the abnormal development of appressoria and conidiophores. Mefentrifluconazole could move acropetally, horizontally, and basipetally in pepper plants. Compared with a knapsack sprayer, mefentrifluconazole applied by mist sprayer exhibited significantly better activity against pepper anthracnose. Additionally, as the spray volume increased from 45 to 150 liters/ha, the control efficacy of mefentrifluconazole first increased and then tended to be steady, with an optimal spray volume of 90 liters/ha. The difference in disease control efficacy was related to the deposition and droplet distribution of mefentrifluconazole on the pepper fruit. These results provide scientific guidance for the application of mefentrifluconazole in pepper fields and improved fungicide utilization.

Nintedanib, an Food and Drug Administration (FDA) approved multiple tyrosine kinase inhibitor, exhibits an anti‐fibrotic effect in lung and kidneys. Its effect on peritoneal fibrosis remains unexplored. In this study, we found that nintedanib administration lessened chlorhexidine gluconate (CG)‐induced peritoneal fibrosis and reduced collagen I and fibronectin expression. This coincided with suppressed phosphorylation of platelet‐derived growth factor receptor, fibroblast growth factor receptors, vascular endothelial growth factor receptor and Src family kinase. Mechanistically, nintedanib inhibited injury‐induced mesothelial‐to‐mesenchymal transition (MMT), as demonstrated by decreased expression of α‐smooth muscle antigen and vimentin and preserved expression of E‐cadherin in the CG‐injured peritoneum and cultured human peritoneal mesothelial cells exposed to transforming growth factor‐β1. Nintedanib also suppressed expression of Snail and Twist, two transcription factors associated with MMT in vivo and in vitro. Moreover, nintedanib treatment inhibited expression of several cytokines/chemokines, including tumour necrosis factor‐α, interleukin‐1β and interleukin‐6, monocyte chemoattractant protein‐1 and prevented infiltration of macrophages to the injured peritoneum. Finally, nintedanib reduced CG‐induced peritoneal vascularization. These data suggest that nintedanib may attenuate peritoneal fibrosis by inhibiting MMT, inflammation, and angiogenesis and have therapeutic potential for the prevention and treatment of peritoneal fibrosis in patients on peritoneal dialysis.

The homodimeric kinesin-2 protein KIF17 functions in intracellular transport and spermiogenesis in mammals. However, its role in fish spermiogenesis has not been reported. Here, we aimed to clone full-length kif17 cDNA and determine the molecular characteristics and expression patterns of KIF17 in Larimichthys polyactis spermiogenesis. The full-length cDNA of L. polyactis kif17 (hp-kif17) was sequenced and found to contain a 332-bp 5′ untranslated region, 480-bp 3′ untranslated region, and 2 433-bp open reading frame encoding 810 amino acids. Bioinformatics analyses showed that L. polyactis KIF17 (Lp-KIF17) shared high sequence similarity with homologs in other animals and possessed an N-terminal motor domain with microtubule-binding sites and adenosine triphosphate (ATP) hydrolysis sites, a stalk domain containing two coiled-coil regions, and a C-terminal tail domain. The Lp-kif17 mRNA was widely expressed in various tissues, with the highest level in the brain, followed by that in the testis. Fluorescence in situ hybridization (FISH) analysis revealed that Lp-kif17 was continuously expressed in spermiogenesis, showing that it had potential functions in this process. Using immunofluorescence (IF) analysis, we found that Lp-KIF17 colocalized with tubulin and was transferred from the perinuclear cytoplasm to the side of spermatid where the tail forms during spermiogenesis. These findings suggested that KIF17 is involved in L. polyactis spermiogenesis. In particular, it may participate in nuclear shaping and tail formation by interacting with perinuclear microtubules during spermatid reshaping. In addition to providing evidence for the role of KIF17 in fish spermatid reshaping, this study provides important data for studies of reproductive biology in L. polyactis.

The harmful algal bloom (HAB) species Pseudo-nitzschia pungens is widely distributed in almost all continents. Accumulating evidence suggests that P. pungens has high genetic diversity and many strains can produce the toxin domoic acid (DA) that harms animals and humans. Nevertheless, different P. pungens strains cannot be distinguished using morphological features or using common molecular markers including 18S rDNA, 28S rDNA, ITS, cox1, and rbcL. As such, high-resolution molecular markers need to be developed to resolve P. pungens genetic diversity, facilitating accurate tracking of toxic P. pungens strains. We hypothesized that molecular markers with high resolution and high specificity can be designed through identifying regions with high genomic variations in the mitochondrial genome. Here, we describe the development of a new molecular marker Pseudo-nitzschia pungens mitochondrial 1 (ppmt1) with high resolution and high specificity through comparative analysis of mitochondrial genomes of nine P. pungens strains isolated from coastal regions of China. In conclusion, we have developed ppmt1 as a high-resolution and high-specificity molecular marker for tracking strains and genetic diversity of the HAB species P. pungens.

CARD9 is an essential adaptor protein in antifungal innate immunity mediated by C-type lectin receptors. The activity of CARD9 is critically regulated by ubiquitination; however, the deubiquitinases involved in CARD9 regulation remain incompletely understood. In this study, we identified ovarian tumor deubiquitinase 1 (OTUD1) as an essential regulator of CARD9. OTUD1 directly interacted with CARD9 and cleaved polyubiquitin chains from CARD9, leading to the activation of the canonical NF-κB and MAPK pathway. OTUD1 deficiency impaired CARD9-mediated signaling and inhibited the proinflammatory cytokine production following fungal stimulation. Importantly, Otud1–/– mice were more susceptible to fungal infection than wild-type mice in vivo. Collectively, our results identify OTUD1 as an essential regulatory component for the CARD9 signaling pathway and antifungal innate immunity through deubiquitinating CARD9.

Members of the Shewanella genus play important roles in bioenergy generation and environmental bioremediation, but their practical applications in engineered systems are still limited due to the la...

The identification of mixed stains has always been a difficult problem in personal identification in the forensic field. In recent years, tissue-specific methylation sites have proven to be very stable biomarkers for distinguishing tissue origin. However, it is still challenging to perform tissue source identification and individual identification simultaneously. In this study, we developed a method that uses tissue-specific methylation markers combined with single-nucleotide polymorphism (SNP) markers to detect semen from mixed biofluids and to identify individuals simultaneously. Semen-specific CpG markers were chosen from the literature and further validated utilizing methylation-sensitive restriction endonuclease (MSRE) combined with PCR technology. The neighboring SNP markers were searched in the flanking sequence of the target CpG within 400 bp, and SNP typing was then carried out through a single-base extension reaction followed by capillary electrophoresis. Eventually, a method of MSRE combined with SNaPshot that could detect 12 compound CpG-SNP markers was developed. Using this system, 10 ng of total DNA and DNA mixture with semen content up to 25% could be typed successfully. Moreover, the cumulative discrimination power of the system in the northern Chinese Han population is 0.9998. This study provides a valuable strategy for forensic practice to perform tissue origin and individual identification from mixed stains simultaneously.

Among succinate dehydrogenase inhibitors, only boscalid has been registered in China for controlling gray mold. In Shandong Province of China, it has been more than a decade since the first use of boscalid to control gray mold. In the current study, we monitored the resistance development process of Botrytis cinerea to boscalid, identified the mutation types that occurred in boscalid-resistant isolates, and proposed an original application technique to delay resistance development. A total of 720 B. cinerea isolates collected from tomato and cucumber in Shandong Province from 2014 to 2019 were determined to be sensitive to boscalid. The results showed that the sensitivity of the B. cinerea isolates to boscalid declined gradually over time, with a mean half maximal effective concentration of 0.3 ± 0.02 mg/liter in 2014 and 6.39 ± 1.66 mg/liter in 2019. The proportion of resistant isolates quickly increased from 0.81% in 2014 to 28.97% in 2019. Mutations of P225F, N230I, H272Y, and H272R in the SdhB subunit were responsible for boscalid resistance. Four concurrent mutations (G85A, I93V, M158V, and V168I) in the SdhC subunit were first discovered in Shandong Province, but they did not affect the level of boscalid resistance. Interestingly, this study found that the fruit dipping application, a precise topical application technique, could delay the development of boscalid resistance. Therefore, this application technique provides a new method for resistance management of B. cinerea.

Background Cottonseed is one of the major sources of vegetable oil. Analysis of the dynamic changes of fatty acid components and the genes regulating the composition of fatty acids of cottonseed oil is of great significance for understanding the biological processes underlying biosynthesis of fatty acids and for genetic improving the oil nutritional qualities. Results In this study, we investigated the dynamic relationship of 13 fatty acid components at 12 developmental time points of cottonseed (Gossypium hirsutum L.) and generated cottonseed transcriptome of the 12 time points. At 5–15 day post anthesis (DPA), the contents of polyunsaturated linolenic acid (C18:3n-3) and saturated stearic acid (C18:0) were higher, while linoleic acid (C18:2n-6) was mainly synthesized after 15 DPA. Using 5 DPA as a reference, 15,647 non-redundant differentially expressed genes were identified in 10–60 DPA cottonseed. Co-expression gene network analysis identified six modules containing 3275 genes significantly associated with middle-late seed developmental stages and enriched with genes related to the linoleic acid metabolic pathway and α-linolenic acid metabolism. Genes (Gh_D03G0588 and Gh_A02G1788) encoding stearoyl-ACP desaturase were identified as hub genes and significantly up-regulated at 25 DPA. They seemed to play a decisive role in determining the ratio of saturated fatty acids to unsaturated fatty acids. FAD2 genes (Gh_A13G1850 and Gh_D13G2238) were highly expressed at 25–50 DPA, eventually leading to the high content of C18:2n-6 in cottonseed. The content of C18:3n-3 was significantly decreased from 5 DPA (7.44%) to 25 DPA (0.11%) and correlated with the expression characteristics of Gh_A09G0848 and Gh_D09G0870. Conclusions These results contribute to our understanding on the relationship between the accumulation pattern of fatty acid components and the expression characteristics of key genes involved in fatty acid biosynthesis during the entire period of cottonseed development.

Fiber length is one of the most important quality parameters of cotton fibers. Transcriptomic analyses of developing cotton fibers have identified genes preferentially expressing in fiber elongation stage, but few have been functionally characterized. Here, on the basis of confirmation of the preferential expression profile of GhAlaRP (Gh_A09G1166 and Gh_D09G1172), an alanine rich protein gene, in the rapid elongating fibers, we investigated the role of GhAlaRP in fiber development by generating transgenic cottons with an increased or decreased expression level of GhAlaRP. Our results showed that the fiber length was consistently significantly shorter in both the GhAlaRP-RNAi lines and the alarp mutant generated by genome editing than in the control YZ-1. GhAlaRP was localized on plasma membrane, nucleus and endoplasmic reticulum. The yeast two-hybrid assay and bimolecular fluorescence complementation assay showed that GhAlaRP co-expresses and interacts with GhAnnexin (Gh_D11G2184) and GhEXPA (Gh_A10G2323) that are involved in fiber elongation. Down-regulation of GhAlaRP co-suppressed the expression levels of GhAnnexin and GhEXPA. These results suggest a role of GhAlaRP in regulation of cotton fiber elongation, which could be achieved by regulating the functions of GhAnnexin and GhEXPA.