Fangyukangsuan granules ameliorate hyperuricemia and modulate gut microbiota in rats.

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.

Transcription factor DIVARICATA1 positively modulates seed germination in response to salinity stress.

Seed germination is a critical checkpoint for plant growth under unfavorable environmental conditions. In Arabidopsis (Arabidopsis thaliana), the abscisic acid (ABA) and gibberellic acid (GA) signaling pathways play important roles in modulating seed germination. However, the molecular links between salinity stress and ABA/GA signaling are not well understood. Herein, we showed that the expression of DIVARICATA1 (DIV1), which encodes a MYB-like transcription factor, was induced by GA and repressed by ABA, salinity, and osmotic stress in germinating seeds. DIV1 positively regulated seed germination in response to salinity stress by directly regulating the expression of DELAY OF GERMINATION 1-LIKE 3 (DOGL3) and GA-STIMULATED ARABIDOPSIS 4 (GASA4) and indirectly regulating the expression of several germination-associated genes. Moreover, NUCLEAR FACTOR-YC9 (NF-YC9) directly repressed the expression of DIV1 in germinating seeds in response to salinity stress. These results help reveal the function of the NF-YC9-DIV1 module and provide insights into the regulation of ABA and GA signaling in response to salinity stress during seed germination in Arabidopsis.

Chromosome-level genome assembly of Przevalski's partridge (Alectoris magna).

Przevalski's partridge (Alectoris magna) is one of the birds in the genus Alectoris endemic to China. The distribution of A. magna was narrow, and it was only found in parts of the Qinghai, Gansu, and Ningxia provinces. A. magna was considered a monotypic species until it was distinguished into two subspecies. However, external morphological characteristics, rather than genetic differences or evolutionary relationships, are now commonly used as evidence of subspecies differentiation. In this study, a chromosome-level reference genome of A. magna has been constructed by combining Illumina, PacBio and Hi-C sequencing data. The 1135.01 Mb A. magna genome was ultimately assembled. The genome showed 96.9% completeness (BUSCO), with a contig N50 length of 23.34 Mb. The contigs were clustered and oriented on 20 chromosomes, covering approximately 99.96% of the genome assembly. Additionally, altogether 19,103 protein-coding genes were predicted, of which 95.10% were functionally annotated. This high-quality genome assembly could serve as a valuable genomic resource for future research on the functional genomics, genetic protection, and interspecific hybridization of A. magna.

The complete mitochondrial genome and phylogenetic analysis of Lepidozona coreanica (Reeve, 1847).

In the present study, the complete mitochondrial genome of Lepidozona coreanica was sequenced and described. The complete mitogenome sequence of L. coreanica is 16,572 bp long and contains 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA) genes. The base composition was AT biased (70.1%). The 13 PCGs of L. coreanica and the other 15 species of Polyplacophora were used for phylogenetic analysis using maximum-likelihood methods. The results showed that L. coreanica, Ischnochiton hakodadensis, and Chaetopleura apiculata are sister groups of the three lineages.

Acute effects of polystyrene nanoplastics on the immune response in Sepia esculenta larvae.

With extensive use of plastic products, microplastics (MPs, < 5 mm) and nanoplastics (NPs, < 1 µm) have become major pollutants in ecosystem, especially in marine environment. In recent years, researches on the impact of NPs on organisms have gradually increased. However, studies on the influence of NPs on cephalopods are still limited. Golden cuttlefish (Sepia esculenta), an important economic cephalopod, is a shallow marine benthic organism. In this study, the effect of acute exposure (4 h) to 50-nm polystyrene nanoplastics (PS-NPs, 100 µg/L) on the immune response of S. esculenta larvae was analyzed via transcriptome data. A total of 1260 DEGs were obtained in the gene expression analysis. The analyses of GO, KEGG signaling pathway enrichment, and protein-protein interaction (PPI) network were then performed to explore the potential molecular mechanisms of the immune response. Finally, 16 key immune-related DEGs were obtained according to the number of KEGG signaling pathways involved and the PPI number. This study not only confirmed that NPs had an impact on cephalopod immune response, but also provided novel insights for further unmasking the toxicological mechanisms of NPs.

Histopathological and transcriptomic analyses reveal the reproductive endocrine-disrupting effects of decabromodiphenyl ethane (DBDPE) in mussel Mytilus galloprovincialis.

The novel brominated flame retardant DBDPE has become a widespread environmental contaminant and could affect reproductive endocrine system in vertebrates. However, information about reproductive endocrine-disrupting effects of DBDPE on invertebrates is totally unknown. In this study, mussels Mytilus galloprovincialis were exposed to 1, 10, 50, 200 and 500 µg/L DBDPE for 30 days. Histopathological and transcriptomic analyses were performed to assess the reproductive endocrine-disrupting effects of DBDPE in mussels and the potential mechanisms. DBDPE promoted the gametogenesis in mussels of both sexes according to histological observation, gender-specific gene expression (VERL and VCL) and histological morphometric parameter analysis. Transcriptomic analysis demonstrated that DBDPE suppressed the genes related to cholesterol homeostasis and transport in both sexes via different LRPs- and ABCs-mediated pathways. DBDPE also disturbed nongenomic signaling pathway including signaling cascades (GPR157-IP3-Ca2+) in males and secondary messengers (cGMP) in females, and subsequently altered the expression levels of reproductive genes (VMO1, ZAN, Banf1 and Hook1). Additionally, dysregulation of energy metabolism in male mussels induced by DBDPE might interfere with the reproductive endocrine system. Overall, this is the first report that DBDPE evoked reproductive endocrine-disruptions in marine mussels. These findings will provide important references for ecological risk assessment of DBDPE pollution in marine environment.

Time-dependent immune injury induced by short-term exposure to nanoplastics in the Sepia esculenta larvae.

Marine organisms are threatened by various environmental contaminants, and nanoplastics (NPs) is one of the most concerned. Studied have shown that NPs has a certain impact on marine organisms, but the specific molecular mechanism is still unclear. At present, researches on the effect of NPs on marine life mostly focus on crustaceans, gastropods, and bivalves. In this study, cephalopod Sepia esculenta larvae were first used to investigate the potential immune response molecular mechanisms caused by PS-NPs (50 nm, 50 mg/L) short-term exposure (4 and 24 h). Through S. esculenta larvae transcriptome profile of gene expression analysis, 548 and 1990 genes showed differential expression at 4 and 24 h after NPs exposure, respectively. GO and KEGG enrichment analysis were performed to find immune related DEGs. Then, the interaction relationship between the immune related DEGs after NPs exposure was known through the constructed protein-protein interaction network. 20 hub genes were found on the base of KEGG pathway numbers involved and protein-protein interaction numbers. This research supply valuable genes for the study of cephalopod immune response caused by NPs, which can help us further uncover the molecular mechanisms of organism against NPs.

Complete mitogenome and phylogenetic analysis of the tropical rocky shore crab Grapsus albolineatus (Lamarck, 1818) (Crustacea: Grapsoidea).

In this study, the complete mitogenome of Grapsus albolineatus (Lamarck, 1818) (Crustacea: Grapsoidea) was sequenced. The mitogenome of G. albolineatus was a circular molecule with 15,578 bp length. Its nucleotide composition was 26.81% A, 16.37% G, 34.51% T, and 22.31% C. It comprised 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), and two ribosomal RNA (rRNA). All PCGs were initiated by ATN codons, except for the atp8 and nad1 genes. Ten PCGs used a common stop codon of TAA or TAG, and the other three ended with a truncated stop codon (a single stop nucleotide T). Phylogenetic analysis revealed that G. albolineatus was closely related to species from the genera Pachygrapsus and Metopograpsus.

A PCSK9 inhibitor induces a transient decrease in the neutrophil-lymphocyte ratio and monocyte-lymphocyte ratio in homozygous familial hypercholesterolemia patients.

Background and aims: Extremely elevated levels of low-density lipoprotein-cholesterol (LDL-C) contribute to long-term chronic systemic inflammation in homozygous familial hypercholesterolemia (HoFH) patients. The aims of this study is to describe the inflammatory profile of HoFH patients and explore the effect of a PCSK9 inhibitor (PCSK9i) on a series of inflammatory biomarkers, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-HDL ratio (MHR), monocyte-lymphocyte ratio (MLR) and mean platelet volume-lymphocyte ratio (MPVLR). Methods: In this prospective cohort study, 25 definitive HoFH patients on high-intensity statins plus ezetimibe were administered subcutaneous injections of 420 mg PCSK9i every 4 weeks (Q4W). The biochemical parameters and inflammatory profile were analyzed on the day before PCSK9i therapy and 3 months and 6 months after PCSK9i therapy. Results: HoFH on the maximum tolerated statin dose plus ezetimibe displayed elevated lipid and disturbed blood biomarker profiles. After 3 months of add-on PCSK9i therapy, a significant reduction in LDL-C was observed. Moreover, the percentage and count of neutrophils, monocyte counts, MPV, and two inflammatory biomarkers, the NLR and MLR, were reduced. However, at 6 months of PCSK9i treatment, the NLR and MLR returned to pre-PCSK9i treatment levels. Conclusions: PCSK9i induces a transient decrease in the NLR and MLR in HoFH patients in a lipid-lowering independent manner.

The Complete Plastid Genomes of Seven Sargassaceae Species and Their Phylogenetic Analysis.

Sargassum is one of the most important genera of the family Sargassaceae in brown algae and is used to produce carrageenan, mannitol, iodine, and other economic substances. Here, seven complete plastid genomes of Sargassum ilicifolium var. conduplicatum, S. graminifolium, S. phyllocystum, S. muticum, S. feldmannii, S. mcclurei, and S. henslowianum were assembled using next-generation sequencing. The sizes of the seven circular genomes ranged from 124,258 to 124,563 bp, with two inverted regions and the same set of plastid genes, including 139 protein-coding genes (PCGs), 28 transfer (t)RNAs, and 6 ribosomal (r)RNAs. Compared with the other five available plastid genomes of Fucales, 136 PCGs were conserved, with two common ones shared with Coccophora langsdorfii, and one with S. fusiforme and S. horneri. The co-linear analysis identified two inversions of trnC(gca) and trnN(gtt) in ten Sargassum species, against S. horneri and C. langsdorfii. The phylogenetic analysis based on the plastid genomes of 55 brown algae (Phaeophyceae) showed four clades, whose ancient ancestor lived around 201.42 million years ago (Mya), and the internal evolutionary branches in Fucales started to be formed 92.52 Mya, while Sargassum species were divided into two subclades 14.33 Mya. Our novel plastid genomes provided evidence for the speciation of brown algae and plastid genomic evolution events.

MODB: a comprehensive mitochondrial genome database for Mollusca.

Mollusca is the largest marine phylum, comprising about 23% of all named marine organisms, Mollusca systematics are still in flux, and an increase in human activities has affected Molluscan reproduction and development, strongly impacting diversity and classification. Therefore, it is necessary to explore the mitochondrial genome of Mollusca. The Mollusca mitochondrial database (MODB) was established for the Life and Health Big Data Center of Yantai University. This database is dedicated to collecting, sorting and sharing basic information regarding mollusks, especially their mitochondrial genome information. We also integrated a series of analysis and visualization tools, such as BLAST, MUSCLE, GENEWISE and LASTZ. In particular, a phylogenetic tree was implemented in this database to visualize the evolutionary relationships between species. The original version contains 616 species whose mitochondrial genomes have been sequenced. The database provides comprehensive information and analysis platform for researchers interested in understanding the biological characteristics of mollusks. Database URL: http://modb.ytu.edu.cn/.

The complete mitochondrial genome and phylogenetic analysis of Neorhodomela munita.

Neorhodomela munita (Perestenko) Masuda 1982 is distributed in the coastal areas of Shandong and Liaoning in China, and also in Japan. In this study, the complete nucleotide sequence of the circular mitochondrial DNA of the red alga Neorhodomela munita has been determined. The complete mitochondrial DNA sequence of Neorhodomela munita was 25,318 bp in length with an overall GC content of 25.1% and encoded 23 protein-coding genes, two ribosomal RNAs and 24 transfer RNAs. Phylogenetic tree showed that Neorhodomela munita clustered together with Choreocolax polysiphoniae. The phylogenetic analysis may provide a better understanding of the evolution of the Rhodophyta species.

A charge sensor integration to tunable double quantum dots on two neighboring InAs nanowires.

A single quantum dot serving as a charge sensor is integrated to scalable double quantum dots using local top finger-gate techniques on two neighboring pure-phase InAs nanowires. The single dot built on one nanowire capacitively couples one of the double dots constructed on another nanowire via a metal bridge gate. The charge occupation states of double quantum dots can be accurately monitored by the sensor even in a few-electron regime in which transport tunneling current through the double dots vanishes. In the tunneling spectroscopy of double dots, electron inter dot tunneling process is absent; however, it can be illustrated by the sensor in terms of a transconductance line between the two closest triple points. Thus, tunnel coupling strength between the double dots is quantitatively extracted from the detectable charge transition. The highly tunable multiple quantum dots with integrated charge sensors on InAs nanowires could be an essential building block for quantum information processing technology.

OGDA: a comprehensive organelle genome database for algae.

Algae are the oldest taxa on Earth, with an evolutionary relationship that spans prokaryotes (Cyanobacteria) and eukaryotes. A long evolutionary history has led to high algal diversity. Their organelle DNAs are characterized by uniparental inheritance and a compact genome structure compared with nuclear genomes; thus, they are efficient molecular tools for the analysis of gene structure, genome structure, organelle function and evolution. However, an integrated organelle genome database for algae, which could enable users to both examine and use relevant data, has not previously been developed. Therefore, to provide an organelle genome platform for algae, we have developed a user-friendly database named Organelle Genome Database for Algae (OGDA, http://ogda.ytu.edu.cn/). OGDA contains organelle genome data either retrieved from several public databases or sequenced in our laboratory (Laboratory of Genetics and Breeding of Marine Organism [MOGBL]), which are continuously updated. The first release of OGDA contains 1055 plastid genomes and 755 mitochondrial genomes. Additionally, a variety of applications have been integrated into this platform to analyze the structural characteristics, collinearity and phylogeny of organellar genomes for algae. This database represents a useful tool for users, enabling the rapid retrieval and analysis of information related to organellar genomes for biological discovery.

Transcriptomic and Proteomic Analysis of Mannitol-metabolism-associated Genes in Saccharina japonica.

As a carbon-storage compound and osmoprotectant in brown algae, mannitol is synthesized and then accumulated at high levels in Saccharina japonica (Sja); however, the underlying control mechanisms have not been studied. Our analysis of genomic and transcriptomic data from Sja shows that mannitol metabolism is a cyclic pathway composed of four distinct steps. A mannitol-1-phosphate dehydrogenase (M1PDH2) and two mannitol-1-phosphatases (M1Pase1 and MIPase2) work together or in combination to exhibit full enzymatic properties. Based on comprehensive transcriptomic data from different tissues, generations, and sexes as well as under different stress conditions, coupled with droplet digital PCR (ddPCR) and proteomic confirmation, we suggest that SjaM1Pase1 plays a major role in mannitol biosynthesis and that the basic mannitol anabolism and the carbohydrate pool dynamics are responsible for carbon storage and anti-stress mechanism. Our proteomic data indicate that mannitol metabolism remains constant during diurnal cycle in Sja. In addition, we discover that mannitol-metabolism-associated (MMA) genes show differential expression between the multicellular filamentous (gametophyte) and large parenchymal thallus (sporophyte) generations and respond differentially to environmental stresses, such as hyposaline and hyperthermia conditions. Our results indicate that the ecophysiological significance of such differentially expressed genes may be attributable to the evolution of heteromorphic generations (filamentous and thallus) and environmental adaptation of Laminariales.

Upregulation of miR-223 abrogates NLRP3 inflammasome-mediated pyroptosis to attenuate oxidized low-density lipoprotein (ox-LDL)-induced cell death in human vascular endothelial cells (ECs).

MiR-223 is closely associated with pathogenesis of coronary artery disease (CAD); however, the molecular mechanisms are unclear. In the present study, the human vascular endothelial cells (ECs) were isolated from patients undergoing coronary artery bypass graft and treated with oxidized low-density lipoprotein (ox-LDL) to induce cellular CAD models in vitro. We found that ox-LDL inhibited cell proliferation and viability, and promoted cell apoptosis in ECs. Of note, ox-LDL promoted cell pyroptosis, and both the pyroptosis inhibitor necrosulfonamide (NSA) and NLRP3 ablation restored cell viability in ECs treated with ox-LDL, indicating that ox-LDL induced EC death by triggering cell pyroptosis. In addition, miR-223 was downregulated by ox-LDL in ECs, and miR-223 overexpression rescued cell viability in ECs treated with ox-LDL. Interestingly, there existed targeting sites in miR-223 and 3' untranslated regions (3' UTRs) of NLRP3 mRNA, and further experiments validated that miR-223 negatively regulated NLRP3 expressions in ECs at both transcriptional and translational levels. Finally, we verified that upregulation of NLRP3 abrogated the protective effects of miR-223 overexpression on ox-LDL-treated ECs. Collectively, this in vitro study proved that overexpression of miR-223 protected ox-LDL-stimulated ECs from death through inactivating NLRP3 inflammasome-mediated pyroptotic cell death.

[Effects of reduced nitrogen application on yield, nitrogen utilization of spring maize and soil nitrate content in Weibei dryland, Northwest China]. / å‡é‡æ–½æ°®å¯¹æ¸­åŒ—æ—±åœ°æ˜¥çŽ‰ç±³äº§é‡ã€æ°®ç´ åˆ©ç”¨åŠåœŸå£¤ç¡æ€æ°®å«é‡çš„å½±å“.

To get a scientific pattern for nitrogen-reducing and efficiency-increasing production of spring maize in Weibei dryland, we conducted an in-situ field experiment of spring maize (Zhengdan 958 and Shaandan 8806) under dryland farming from 2016 to 2019 in Heyang County, located in Weibei dryland of Shaanxi. There were five nitrogen (N) treatments, including 360 kg·hm-2(N360, a rate commonly adopted by local farm households), 270 kg·hm-2(N270), 150-180 kg·hm-2(N150-180), 75-90 kg·hm-2(N75-90) and 0 kg·hm-2(N0). We investigated the effects of reduced nitrogen application on maize yield, nitrogen uptake and utilization of spring maize and soil nitrate residue. The results showed that: 1) Maize yield of both varieties at N150-180 was increased by 0.9%-7.1% and nitrogen uptake was decreased by 4.1%-4.6%, while average reco-very efficiency, partial-factor productivity and agronomic efficiency of N at N150-180 were increased by 79.3%-83.6%, 105.9%-157.7%, and 101.9%-114.1% compared with those at N360, respectively. 2) The contents of residual nitrate increased significantly when nitrogen application rate was more than 180 kg·hm-2, while nitrogen uptake was significantly reduced under rainfall shortage, and thus resulted in increasing soil residual nitrogen. After four-year treatments, the residual nitrate was up to 504.7-620.8 kg·hm-2 in 0-200 cm soil layer, with a peak in 80-140 cm soil layer. There was a risk of nitrate leaching. According to the comprehensive evaluation for annual yield, nitrogen use efficiency and soil nitrate residue, the optimum N application rate was recommended to be 150-180 kg N·hm-2 for spring maize in Weibei dryland.

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study.

BACKGROUND: Homozygous familial hypercholesterolemia (hoFH) is a rare inherited disorder characterized by extreme elevation of low-density lipoprotein (LDL) cholesterol, accelerated coronary artery disease, and premature death. Aggressive LDL-lowering therapies are important for survival, but these are not available worldwide. OBJECTIVE: The aim of the study was to compare and contrast cardiovascular outcomes and mortality of hoFH patients in 2 countries with disparate use of lipoprotein apheresis (LA) and modern therapies for lowering LDL cholesterol. METHODS: A retrospective study was undertaken comparing cardiovascular disease (CVD)-free survival and mortality in 44 hoFH patients who were treated with statins but not LA, from a center in Beijing, China, and 18 hoFH patients who were treated with LA and novel therapies from an early age, from a center in Rome, Italy. RESULTS: CVD-free survival and survival were significantly reduced in Chinese patients compared with the Italian patients after 30 years of follow-up (log-rank P < .01). In a pooled analysis, cardiovascular survival was significantly increased with earlier age at treatment, longer duration of treatment, and lower on-treatment LDL cholesterol concentrations (P < .05). In addition, the probability of a CVD event and death were increased in patients that carried a null mutation in the LDLR or had elevated lipoprotein(a). CONCLUSIONS: We show that coronary artery disease outcomes in patients with hoFH can be significantly improved with earlier and potent LDL cholesterol lowering with pharmacotherapies and LA. This has major implications for countries, such as China, where the models of care for hoFH remains underdeveloped.

Evolution of Complex Thallus Alga: Genome Sequencing of Saccharina japonica.

Saccharina, as one of the most important brown algae (Phaeophyceae) with multicellular thallus, has a very remarkable evolutionary history, and globally accounts for most of the economic marine aquaculture production worldwide. Here, we present the 580.5 million base pairs of genome sequence of Saccharina japonica, whose current assembly contains 35,725 protein-coding genes. In a comparative analysis with Ectocarpus siliculosus, the integrated virus sequence suggested the genome evolutionary footprints, which derived from their co-ancestry and experienced genomic arrangements. Furthermore, the gene expansion was found to be an important strategy for functional evolution, especially with regard to extracelluar components, stress-related genes, and vanadium-dependent haloperoxidases, and we proposed a hypothesis that gene duplication events were the main driving force for the evolution history from multicellular filamentous algae to thallus algae. The sequenced Saccharina genome paves the way for further molecular studies and is useful for genome-assisted breeding of S. japonica and other related algae species.