Systematic identification and expression analysis of bHLH gene family reveal their relevance to abiotic stress response and anthocyanin biosynthesis in sweetpotato.

BACKGROUND: bHLH transcription factors play significant roles in regulating plant growth and development, stress response, and anthocyanin biosynthesis. Sweetpotato is a pivotal food and industry crop, but little information is available on sweetpotato bHLH genes. RESULTS: Herein, 227 putative IbbHLH genes were defined on sweetpotato chromosomes, and fragment duplications were identified as the dominant driving force for IbbHLH expansion. These IbbHLHs were divided into 26 subfamilies through phylogenetic analysis, as supported by further analysis of exon-intron structure and conserved motif composition. The syntenic analysis between IbbHLHs and their orthologs from other plants depicted evolutionary relationships of IbbHLHs. Based on the transcriptome data under salt stress, the expression of 12 IbbHLHs was screened for validation by qRT-PCR, and differential and significant transcriptions under abiotic stress were detected. Moreover, IbbHLH123 and IbbHLH215, which were remarkably upregulated by stress treatments, had obvious transactivation activity in yeasts. Protein interaction detections and yeast two-hybrid assays suggested an intricate interaction correlation between IbbHLHs. Besides, transcriptome screening revealed that multiple IbbHLHs may be closely related to anthocyanin biosynthesis based on the phenotype (purple vs. white tissues), which was confirmed by subsequent qRT-PCR analysis. CONCLUSIONS: These results shed light on the promising functions of sweetpotato IbbHLHs in abiotic stress response and anthocyanin biosynthesis.

Evidence from 2100 index cases supports genome sequencing as a first-tier genetic test.

PURPOSE: Genome sequencing (GS) is one of the most comprehensive assays that interrogate single-nucleotide variants, copy number variants, mitochondrial variants, repeat expansions, and structural variants in a single assay. Despite the clear technical superiority, the full clinical utility of GS has yet to be determined. METHODS: We systematically evaluated 2100 clinical GS index cases performed in our laboratory to explore the diagnostic yield of GS as first-tier and as follow-up testing. RESULTS: The overall diagnostic yield was 28% (585/2100). The diagnostic yield for GS as the first-tier test was 26% (294/1146). Among cases with prior non-diagnostic genetic tests, GS provided a diagnosis for 27% (247/910) of cases, including 56 cases with prior exome sequencing (ES). Although re-analysis of previous ES might have resolved the diagnosis in 29 cases, diagnoses for 27 cases would have been missed because of the technical inferiority of ES. Moreover, GS further disclosed additional genetic etiology in 3 out of 44 cases with existing partial diagnosis. CONCLUSION: We present the largest-to-date GS data set of a clinically heterogeneous cohort from a single clinical laboratory. Our data demonstrate that GS should be considered as the first-tier genetic test that has the potential to shorten the diagnostic odyssey.

The unique sweet potato NAC transcription factor IbNAC3 modulates combined salt and drought stresses.

Plants often simultaneously experience combined stresses rather than a single stress, causing more serious damage, but the underlying mechanisms remain unknown. Here, we identified the stress-induced IbNAC3 from sweet potato (Ipomoea batatas) as a nucleus-localized transcription activator. IbNAC3 contains a unique activation domain whose MKD sequence confers transactivation activities to multiple other TFs and is essential for the activated expression of downstream target genes. Ectopic expression of IbNAC3 conferred tolerance to single and combined salt and drought stresses in Arabidopsis (Arabidopsis thaliana), and a group of NAM, ATAF1/2, and CUC2 (NAC) TFs, including ANAC011, ANAC072, ANAC083, ANAC100, and NAP, interacted with IbNAC3, and the specific domains responsible for each interaction varied. Intriguingly, IbNAC3 repressed the interaction among the five NACs, and knockout or mutation of ANAC011 and ANAC072 dramatically impaired combined stress tolerance. IbNAC3-ANAC072 and IbNAC3-NAP modules synergistically activated the MICROTUBULE-RELATED E3 LIGASE57 (MREL57) gene. Consistently, mutation of MREL57 and overexpression of WAVE-DAM-PENED2-LIKE7, encoding a target protein of MREL57, both remarkably impaired combined stress tolerance. Moreover, transgenic plants displayed abscisic acid (ABA) hyposensitivity by directly promoting the transcription of ENHANCED RESPONSE TO ABA 1, a key negative regulator of ABA signaling. The data unravel the unique IbNAC3 TF functions as a pivotal component in combined stress tolerance by integrating multiple regulatory events and ubiquitin pathways, which is essential for developing high-tolerant plants in natural environments.

Assessing the impact of river connectivity on fish biodiversity in the Yangtze River Basin using a multi-index evaluation framework.

The Yangtze River Basin, the world's third-largest river basin and a hot spot for global biodiversity conservation, is facing biodiversity crisis caused by reduced river connectivity. The deterioration arises from four dimensions: longitudinal, lateral, vertical and temporal. However, limited research has quantified the spatiotemporal connectivity of the Yangtze River Basin and further evaluated the consequent impact on fish biodiversity. In our study, a multi-index evaluation framework was developed to assess the variations in the four-dimensional connectivity of the Yangtze River Basin from 1980 to 2020, and fish biodiversity affected by reduced connectivity was detected by environmental DNA metabarcoding. Our results showed that the Yangtze River Basin suffers from a pronounced connectivity reduction, with 67% of assessed rivers experiencing deteriorated connectivity in recent years. The lost fish biodiversity along the river reaches with the worst connectivity was likely attributed to the construction of hydropower plants. The headwaters and the downstreams of most hydropower plants had a higher fish biodiversity compared with reservoirs. The free-flowing reaches in the downstream of the lowest hydropower station, had higher lotic fish abundance compared with that in the upstream. As for the entire Yangtze River Basin, 67% of threatened fish species, with 70% endemic species, were threatened by reduced river connectivity. Our result indicates that the massive loss of river connectivity changes the spatiotemporal patterns of fish community and threatens protected fish. More effective measures to restore the populations of affected fish in rivers with reduced river connectivity are required.

Estimating the temporal and spatial distribution and threats of bisphenol A in temperate lakes using machine learning models.

Bisphenol A (BPA) is easily enriched in many human-disturbed watersheds, particularly lakes with poor water mobility, which is posing a threat to aquatic biota. While previous studies have focused on the concentration of BPA in water and its toxicity to aquatic organisms, a small amount of measured data is not enough to reveal the temporal and spatial distribution and threats of BPA, and estimate the ecological risk in watersheds. Therefore, we collected 164 measured BPA data points from Taihu Lake to develop machine learning models using random forest (RF), support vector machine (SVM) and least square regression (LSR) and created month-by-month watershed prediction maps in temperate lakes to estimate the spatiotemporal distribution and threats of BPA. Due to RF's superior robustness to noisy data, the RF model exhibits the best performance among the three algorithms. The RF model showed acceptable predictive performance on the modeling dataset (coefficients of determination and root-mean-square error for the training set were 0.927 and 17.499, respectively, and 0.607, 39.645 for the validation set, respectively). The maps indicated that areas susceptible to anthropogenic activities were more severely polluted by BPA, and rainy climate may favor the migration of BPA to aquatic ecosystems. The model was also applied to predict 42 data points of BPA collected from Dianchi Lake, and the results showed that most predicted data were within a factor of 10 of the measured data, but the prediction accuracy of the model has declined. The ecological risks in the two lakes were evaluated and attention should be paid to the regions with higher risks. Our study provided a novel idea for comprehensive monitoring of an unconventional trace pollutant with endocrine disrupting effects in aquatic ecosystems and analyzing their spatiotemporal distribution, which will contribute to the scientific assessment of the ecological risk of BPA.

Environmental DNA and remote sensing datasets reveal the spatial distribution of aquatic insects in a disturbed subtropical river system.

Biodiversity datasets with high spatial resolution are critical prerequisites for river protection and management decision-making. However, traditional morphological biomonitoring is inefficient and only provides several site estimates, and there is an urgent need for new approaches to predict biodiversity on fine spatial scales throughout the entire river systems. Here, we combined the environmental DNA (eDNA) and remote sensing (RS) technologies to develop a novel approach for predicting the spatial distribution of aquatic insects with high spatial resolution in a disturbed subtropical Dongjiang River system of southeast China. First, we screened thirteen RS-based vegetation indices that significantly correlated with the eDNA-inferred richness of aquatic insects. In particular, the green normalized difference vegetation index (GNDVI) and normalized difference red-edge2 (NDRE2) were closely related to eDNA-inferred richness. Second, using the gradient boosting decision tree, our data showed that the spatial pattern of eDNA-inferred richness could achieve a high spatial resolution to 500 m reach and accurate prediction of more than 80%, and the prediction efficiency of the headwater streams (Strahler stream order = 1) was slightly higher than the downstream (Strahler stream order >1). Third, using the random forest algorithm, the spatial distribution of aquatic insects could reach a prediction rate of over 70% for the presence or absence of specific genera. Overall, this study provides a new approach to achieving high spatial resolution prediction of the distribution of aquatic insects, which supports decision-making on river diversity protection under climate changes and human impacts.

How do small dams alter river food webs? A food quality perspective along the aquatic food web continuum.

Damming of rivers poses a significant threat to freshwater ecosystems. Previous studies about the impact of damming on river ecosystems have mostly focused on large dams, with the impact of small dams largely unknown. Further, while the impacts of dams on aquatic communities have been widely studied, the effect on energy flow across river food webs remains unclear. In recent years, long-chain polyunsaturated fatty acid analysis (LC-PUFA) has emerged as a promising technique for assessing food quality and trophic interactions. In this study, LC-PUFA was applied to explore the nutritional effects of small dams on river food webs. A field investigation was conducted at upstream and downstream areas of three small dams in the headwaters of Dongjiang River, China, to evaluate the impact of small dams on the nutritional quality of basal food sources, and their consequent impacts on aquatic consumers and trophic links. Basal food sources (i.e., submerged leaves, macrophytes and periphyton) and aquatic consumers (i.e., macroinvertebrates and fish) were collected, and their fatty acid (FA) composition was measured. Our results showed that periphyton, rather than submerged leaves and macrophytes, was the primary high-quality food source for aquatic consumers, providing them with LC-PUFA, irrespective of whether sites were upstream or downstream. Damming the streams induced changes in aqueous nutrient concentrations (TP, PO4-P, DIN, and TN) from upstream to downstream of the dams, leading to significant variation in periphyton FA content. Compared with periphyton collected at downstream sites, periphyton at upstream sites contained higher LC-PUFA, but lower short-chain PUFA. Differences in periphyton LC-PUFA between the upstream and downstream areas of dams were reflected in the FA profiles of invertebrate grazers and filterers, and further transferred to fish. Furthermore, decreased periphyton nutritional quality at the downstream of the dams was one of the reasons for the simplification of stream food webs. Our results indicated that small dams negatively affected food webs, emphasizing the importance of high-quality food sources for stream ecosystems. We suggest that the trophic integrity of river food webs hinges on the dietary availability of periphyton supplying physiologically highly required nutrients for consumers and must thus not be compromised by damming of streams or other alterations.

Ni(OH)2 surface-modified hierarchical ZnIn2S4 nanosheets: dual photocatalytic application and mechanistic insights.

The simultaneous utilization of electrons and holes to couple photocatalytic H2 production with selective biomass transformation has attracted immense interest toward achieving sustainability in the fields of energy and chemical industry. In this study, by assembling highly dispersed Ni(OH)2 onto ZnIn2S4 (ZIS), efficient H2 evolution along with highly selective photocatalytic oxidation of furfuryl alcohol (FA) to furfural (FF) in pure water was achieved under anaerobic conditions. The H2 production and FA conversion rates over the optimal Ni-ZIS sample reached about 686 and 583 µmol g-1 h-1, respectively, about 4.9 and 1.7 folds as those of pure ZIS. Moreover, the formation of by-products with C-C coupling was dramatically suppressed over Ni-ZIS, resulting in higher selectivity for FF (97%), which is about 2.7-fold that of pure ZIS (36%). Deep mechanistic studies were conducted to reveal the structural evolution and cocatalyst effects of Ni(OH)2. This study not only offers a feasible paradigm for modifying the surface of catalysts to tune the photoactivity and selectivity for product-oriented alcohol oxidation coupled with efficient H2 production in water but also reveals the working mechanism of the deposited Ni(OH)2 over ZIS toward coupling reactions.

Antibacterial lanostane triterpenoids from Ganoderma tsugae.

A phytochemical investigation on the 80% EtOH extract of the fruiting bodies of Ganoderma tsugae resulted into the isolation of two previously undescribed lanostane triterpenoids, 7,11-dioxo-3ß-acetyloxy-26,27-dihydroxy-lanosta-8,24-diene (1) and 7,20-dioxo-3ß-acetyloxy-11ß,15α-dihydroxy-22,23,24,25,26,27-hexanorlanosta-8-ene (2), togeher with one known lanostane triterpenoid ganodermanontriol (3). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. All the triterpenoids were in vitro evaluated for their antibacterial activities against six pathogenic microorganisms. Compound 3 exhibited some activities against three Gram positive bacteria with MIC values less than 30 µg/ml.

A Modified 1H-NMR Quantification Method of Ephedrine Alkaloids in Ephedrae Herba Samples.

A previous 1H-NMR method allowed the quantification of ephedrine alkaloids; however, there were some disadvantages. The cyclized derivatives resulted from the impurities of diethyl ether were identified and benzene was selected as the better extraction solvent. The locations of ephedrine alkaloids were confirmed with 2D NMR. Therefore, a specific 1H-NMR method has been modified for the quantification of ephedrine alkaloids. Accordingly, twenty Ephedrae Herba samples could be classified into three classes: (I) E. sinica-like species; (II) E. intermedia-like species; (III) others (lower alkaloid contents). The results indicated that ephedrine and pseudoephedrine are the major alkaloids in Ephedra plants, but the concentrations vary greatly determined by the plant species and the collection locations.

Long-term exercise at different intensities can reduce the inflammatory response in the brains of methamphetamine-treated mice.

Methamphetamine (METH) is a highly addictive psychoactive drug that is used worldwide. Various approaches have been used to address METH dependence, but many of them have little effect. Previous studies have shown that exercise on a treadmill could reduce METH dependence in mice, but the intensity and duration of exercise that was needed to be effective was unknown. This study investigated the effects of low- and medium-intensity treadmill exercise on methamphetamine reward in male mice via conditioned place preference (CPP) training, and the levels of the inflammatory factors IL-1ß, IL-6 and TNF-α in three brain regions (cerebral cortex, hippocampus and striatum) were determined. The results showed that long-term medium-intensity exercise reduced the effects of methamphetamine on inflammation markers in the brain and CPP scores. In addition, long-term medium-intensity exercise decreased IL-1ß concentrations in the cerebral cortex and hippocampus, reduced IL-6 concentrations in the striatum, and reduced TNF-α concentrations in the cerebral cortex, hippocampus, and striatum in methamphetamine-treated mice; low-intensity exercise was less effective. The results indicated that long-term medium-intensity exercise could reduce concentrations of methamphetamine-induced encephalitis factors in male mice, while low-intensity exercise was less effective in alleviating dependence and inflammatory responses. It is suggested that exercise intensity is an important factor affecting the dependence level and inflammatory responses in the brain in mice administered methamphetamine.

A systematical genome-wide analysis and screening of WRKY transcription factor family engaged in abiotic stress response in sweetpotato.

BACKGROUND: WRKY transcription factors play pivotal roles in regulating plant multiple abiotic stress tolerance, however, a genome-wide systematical analysis of WRKY genes in sweetpotato is still missing. RESULTS: Herein, 84 putative IbWRKYs with WRKY element sequence variants were identified in sweetpotato reference genomes. Fragment duplications, rather than tandem duplications, were shown to play prominent roles in IbWRKY gene expansion. The collinearity analysis between IbWRKYs and the related orthologs from other plants further depicted evolutionary insights into IbWRKYs. Phylogenetic relationships displayed that IbWRKYs were divided into three main groups (I, II and III), with the support of the characteristics of exon-intron structures and conserved protein motifs. The IbWRKY genes, mainly from the group Ib, displayed remarkable and diverse expression profiles under multiple abiotic stress (NaCl, PEG6000, cold and heat) and hormone (ABA, ACC, JA and SA) treatments, which were determined by RNA-seq and qRT-PCR assays, suggesting their potential roles in mediating particular stress responses. Moreover, IbWRKY58L could interact with IbWRKY82 as revealed by yeast two-hybrid based on the protein interaction network screening. And abiotic stress-remarkably induced IbWRKY21L and IbWRKY51 were shown to be localized in the nucleus and had no transactivation activities. CONCLUSION: These results provide valuable insights into sweetpotato IbWRKYs and will lay a foundation for further exploring functions and possible regulatory mechanisms of IbWRKYs in abiotic stress tolerance.

Genome-wide survey and expression analysis of GRAS transcription factor family in sweetpotato provides insights into their potential roles in stress response.

BACKGROUND: The plant-specific GRAS transcription factors play pivotal roles in various adverse environmental conditions. Numerous GRAS genes have been explored and characterized in different plants, however, comprehensive survey on GRASs in sweetpotato is lagging. RESULTS: In this study, 72 putative sweetpotato IbGRAS genes with uneven distribution were isolated on 15 chromosomes and classified into 12 subfamilies supported by gene structures and motif compositions. Moreover, both tandem duplication and segmental duplication events played critical roles in the expansion of sweetpotato GRAS genes, and the collinearity between IbGRAS genes and the related orthologs from nine other plants further depicted evolutionary insights into GRAS gene family. RNA-seq analysis under salt stress and qRT-PCR detection of 12 selected IbGRAS genes demonstrated their significant and varying inductions under multiple abiotic stresses (salt, drought, heat and cold) and hormone treatments (ABA, ACC and JA). Consistently, the promoter regions of IbGRAS genes harbored a series of stress- and hormone-associated cis-acting elements. Among them, IbGRAS71, the potential candidate for breeding tolerant plants, was characterized as having transactivation activity in yeasts, while IbGRAS-2/-4/-9 did not. Moreover, a complex interaction relationship between IbGRASs was observed through the interaction network analysis and yeast two-hybrid assays. CONCLUSIONS: Our results laid a foundation for further functional identifications of IbGRAS genes, and multiple members may serve as potential regulators for molecular breeding of tolerant sweetpotato.

Environmental DNA Biomonitoring Reveals the Interactive Effects of Dams and Nutrient Enrichment on Aquatic Multitrophic Communities.

Dam construction and nutrient enrichment are two pervasive stressors in rivers worldwide, which trigger a sharp decline in biodiversity and ecosystem services. However, the interactive effects of both stressors on multitrophic taxonomic groups remain largely unclear. Here, we used the multitrophic datasets captured by the environmental DNA (eDNA) approach to reveal the interactions between dams and nutrient enrichment on aquatic communities from the aspects of taxonomic α diversity, ß diversity, and food webs. First, our data showed that dams and nutrient enrichment jointly shaped a unique spatial pattern of aquatic communities across the four river systems, and the dissimilarity of community structure significantly declined (i.e., structural homogenization) under both stressors. Second, dams and nutrients together explained 40-50% of the variations in aquatic communities, and dams had a stronger impact on fish, aquatic insects, and bacteria, yet nutrients had a stronger power to drive protozoa, fungi, and eukaryotic algae. Finally, we found that additive, synergistic, and antagonistic interactions of dams and nutrient enrichment were common and coexisted in river systems and led to significantly simplified aquatic food webs, with decreases in modularity (synergistic) and robustness (additive) and an increase in coherence (synergistic). Overall, our study highlights that eDNA-based datasets can provide multitrophic perspectives for fostering the understanding of the interactive effects of multiple stressors on rivers.

Assessment of Compound-Specific Fatty Acid δ13C and δ2H Values to Track Fish Mobility in a Small Sub-alpine Catchment.

Methods for identifying origin, movement, and foraging areas of animals are essential for understanding ecosystem connectivity, nutrient flows, and other ecological processes. Telemetric methods can provide detailed spatial coverage but are limited to a minimum body size of specimen for tagging. In recent years, stable isotopes have been increasingly used to track animal migration by linking landscape isotope patterns into movement (isoscapes). However, compared to telemetric methods, the spatial resolution of bulk stable isotopes is low. Here, we examined a novel approach by evaluating the use of compound-specific hydrogen and carbon stable isotopes of fatty acids (δ2HFA and δ13CFA) from fish liver, muscle, brain, and eye tissues for identifying site specificity in a 254 km2 sub-alpine river catchment. We analyzed 208 fish (European bullhead, rainbow trout, and brown trout) collected in 2016 and 2018 at 15 different sites. δ13CFA values of these fish tissues correlated more among each other than those of δ2HFA values. Both δ2HFA and δ13CFA values showed tissue-dependent isotopic fractionation, while fish taxa had only small effects. The highest site specificity was for δ13CDHA values, while the δ2H isotopic difference between linoleic acid and alpha-linolenic acid resulted in the highest site specificity. Using linear discrimination analysis of FA isotope values, over 90% of fish could be assigned to their location of origin; however, the accuracy dropped to about 56% when isotope data from 2016 were used to predict the sites for samples collected in 2018, suggesting temporal shifts in site specificity of δ2HFA and δ13CFA. However, the predictive power of δ2HFA and δ13CFA over this time interval was still higher than site specificity of bulk tissue isotopes for a single time point. In summary, compound-specific isotope analysis of fatty acids may become a highly effective tool for assessing fine and large-scale movement and foraging areas of animals.

Spatial Attention Frustum: A 3D Object Detection Method Focusing on Occluded Objects.

Achieving the accurate perception of occluded objects for autonomous vehicles is a challenging problem. Human vision can always quickly locate important object regions in complex external scenes, while other regions are only roughly analysed or ignored, defined as the visual attention mechanism. However, the perception system of autonomous vehicles cannot know which part of the point cloud is in the region of interest. Therefore, it is meaningful to explore how to use the visual attention mechanism in the perception system of autonomous driving. In this paper, we propose the model of the spatial attention frustum to solve object occlusion in 3D object detection. The spatial attention frustum can suppress unimportant features and allocate limited neural computing resources to critical parts of the scene, thereby providing greater relevance and easier processing for higher-level perceptual reasoning tasks. To ensure that our method maintains good reasoning ability when faced with occluded objects with only a partial structure, we propose a local feature aggregation module to capture more complex local features of the point cloud. Finally, we discuss the projection constraint relationship between the 3D bounding box and the 2D bounding box and propose a joint anchor box projection loss function, which will help to improve the overall performance of our method. The results of the KITTI dataset show that our proposed method can effectively improve the detection accuracy of occluded objects. Our method achieves 89.46%, 79.91% and 75.53% detection accuracy in the easy, moderate, and hard difficulty levels of the car category, and achieves a 6.97% performance improvement especially in the hard category with a high degree of occlusion. Our one-stage method does not need to rely on another refining stage, comparable to the accuracy of the two-stage method.

Longitudinal variation in the nutritional quality of basal food sources and its effect on invertebrates and fish in subalpine rivers.

There is growing recognition of the importance of food quality over quantity for aquatic consumers. In streams and rivers, most previous studies considered this primarily in terms of the quality of terrestrial leaf litter and importance of microbial conditioning. However, many recent studies suggest that algae are a more nutritional food source for riverine consumers than leaf litter. To date, few studies have quantified longitudinal shifts in the nutritional quality of basal food resources in river ecosystems and how these may affect consumers. We conducted a field investigation in a subalpine river ecosystem in Austria to investigate longitudinal variations in diet quality of basal food sources (submerged leaves and periphyton) and diet source dependence of stream consumers (invertebrate grazers, shredders, filterers and predators, and fish). Fatty acid (FA) profiles of basal food sources and their consumers were measured. Our results indicate systematic differences between the FA profiles of terrestrial leaves and aquatic biota, that is periphyton, invertebrates and fish. Submerged leaves contained very low proportions of long-chain polyunsaturated fatty acids (LC-PUFAs), which were conversely rich in aquatic biota. While the FA composition of submerged leaves remained similar among sites, the LC-PUFAs of periphyton increased longitudinally, which was associated with increasing nutrients from upstream to downstream. Longitudinal variations in periphyton LC-PUFAs were reflected in the LC-PUFAs of invertebrate grazers and shredders, and further tracked by invertebrate predators and fish. However, brown trout Salmo trutta contained a large proportion of docosahexaenoic acid (DHA, 22:6ω3), a LC-PUFA almost entirely missing in basal sources and invertebrates. The fish accumulated eicosapentaenoic acid (EPA, 20:5ω3) from invertebrate prey and may use this FA to synthesize DHA. Our results provide a nutritional perspective for river food web studies, emphasizing the importance of algal resources to consumer somatic growth and the need to account for the longitudinal shifts in the quality of these basal resources.

The baroreflex afferent pathway plays a critical role in H2S-mediated autonomic control of blood pressure regulation under physiological and hypertensive conditions.

Hydrogen sulfide (H2S), which is closely related to various cardiovascular disorders, lowers blood pressure (BP), but whether this action is mediated via the modification of baroreflex afferent function has not been elucidated. Therefore, the current study aimed to investigate the role of the baroreflex afferent pathway in H2S-mediated autonomic control of BP regulation. The results showed that baroreflex sensitivity (BRS) was increased by acute intravenous NaHS (a H2S donor) administration to renovascular hypertensive (RVH) and control rats. Molecular expression data also showed that the expression levels of critical enzymes related to H2S were aberrantly downregulated in the nodose ganglion (NG) and nucleus tractus solitarius (NTS) in RVH rats. A clear reduction in BP by the microinjection of NaHS or L-cysteine into the NG was confirmed in both RVH and control rats, and a less dramatic effect was observed in model rats. Furthermore, the beneficial effects of NaHS administered by chronic intraperitoneal infusion on dysregulated systolic blood pressure (SBP), cardiac parameters, and BRS were verified in RVH rats. Moreover, the increase in BRS was attributed to activation and upregulation of the ATP-sensitive potassium (KATP) channels Kir6.2 and SUR1, which are functionally expressed in the NG and NTS. In summary, H2S plays a crucial role in the autonomic control of BP regulation by improving baroreflex afferent function due at least in part to increased KATP channel expression in the baroreflex afferent pathway under physiological and hypertensive conditions.

Protective effects of irigenin against 1-methyl-4-phenylpyridinium-induced neurotoxicity through regulating the Keap1/Nrf2 pathway.

The rhizome of Belamcanda chinensis possesses antiinflammatory and antioxidant activities. However, the effect of irigenin, isolated from the rhizome of B. chinensis, on 1-methyl-4-phenylpyridinium (MPP+ )-induced neurotoxicity is unknown. MTT assay showed that MPP+ exposure dose dependently inhibited the viability of mouse microglia BV-2 cells, whereas irigenin suppressed MPP+ -induced viability reduction. The production of nitric oxide, prostaglandin E2, tumor necrosis factor-α and interleukin-6 were increased by MPP+ treatment, which were abolished by irigenin treatment. Irigenin-attenuated MPP+ -induced increase of malondialdehyde content and activities of superoxide dismutase, catalase and glutathione peroxidase in BV-2 cells. Irigenin treatment also repressed apoptosis, caspase-3/7 activity and Cytochrome C expression in MPP+ -challenged BV-2 cells. Interestingly, irigenin activated the Keap1/Nrf2 pathway in MPP+ -induced BV-2 cells. Nrf2 knockdown attenuated the effects of irigenin on MPP+ -induced viability reduction, inflammation, oxidative stress and apoptosis in BV-2 cells. In conclusion, irigenin alleviated MPP+ -induced neurotoxicity in BV-2 cells through regulating the Keap1/Nrf2 pathway.

Chromosomal instability upregulates interferon in acute myeloid leukemia.

Chromosome instability (CIN) generates genetic and karyotypic diversity that is common in hematological malignancies. Low to moderate levels of CIN are well tolerated and can promote cancer proliferation. However, high levels of CIN are lethal. Thus, CIN may serve both as a prognostic factor to predict clinical outcome and as a predictive biomarker. A retrospective study was performed to evaluate CIN in acute myeloid leukemia (AML). Chromosome mis-segregation frequency was correlated with clinical outcome in bone marrow core biopsy specimens from 17 AML cases. Additionally, we induced chromosome segregation errors in AML cell lines with AZ3146, an inhibitor of the Mps1 mitotic checkpoint kinase, to quantify the phenotypic effects of high CIN. We observed a broad distribution of chromosome mis-segregation frequency in AML bone marrow core specimens. High CIN correlated with complex karyotype in AML, as expected, although there was no clear survival effect. In addition to CIN, experimentally inducing chromosome segregation errors by Mps1 inhibition in AML cell lines causes DNA damage, micronuclei formation, and upregulation of interferon stimulated genes. High levels of CIN appear to be immunostimulatory, suggesting an opportunity to combine mitotic checkpoint inhibitors with immunotherapy in treatment of AML.