Two complete mitochondrial genomes in Scolopendra and a comparative analysis of tRNA rearrangements in centipedes.

BACKGROUND: Centipedes are one of the oldest terrestrial arthropods belonging to the sub phylum Myriapoda. With the expansion of our understanding of the application of the two centipedes Scolopendra morsitans and Scolopendra hainanum, belonging to the order Scolopendromorpha, an exhaustive classification was required. Although consensus has been reached on the phylogeny of Chilopoda based on morphological traits, recent analyses based on molecular data exhibited differences in results. METHODS AND RESULTS: The mitochondrial genome sequences of S. morsitans and S. hainanum were obtained by next-generation sequencing. S. morsitans contains 13 PCGs, two rRNAs, 11 tRNAs, and one CR. whereas S. hainanum contains 12 PCGs, of which ATP8 remains unpredicted, two rRNAs, 14 tRNAs, and one CR. An obvious tRNA rearrangement was found in the genus Scolopendra. S. morsitans exhibited a loss of trnW, trnC, trnI, trnK, trnD, trnA, trnN, trnQ, trnF, trnT, trnS, trnL, and trnV, and a repeat of trnR and trnL. S. hainanum exhibited a loss of trnQ, trnC, trnW, trnI, trnD, trnQ, trnP, and trnV. Phylogenetic analyses of centipedes based on 12 PCGs supported the sister relationship between the orders Geophilomorpha and Lithobiomorpha and a close relationship between Scolopendra dehaani and S. hainanum. CONCLUSIONS: The new mitogenomes determined in this study provide new genomic resources for gene rearrangements and contribute to the understanding of the evolution of gene rearrangement in Chilopoda.

Integrated Bioinformatics Analysis Identifies microRNA-200a-5p as a New Plasma Marker in Patients with Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a major global health problem with high incidence and mortality. Vein endothelial cell (VEC) dysfunction is the primary cause of VTE. MicroRNAs (miRNAs) assist in the regulation of VEC functional pathways. Our objective was to identify potential miRNA target genes associated with VTE. MATERIALS AND METHODS: To explore the association between mRNAs and miRNAs in VTE, we performed an mRNA or miRNA microarray analysis and experiments in vitro. In addition, five online bioinformatics tools identified the target genes of differentially expressed miRNAs, and a miRNA-gene network was constructed. As a result, hub miRNA and mRNA were confirmed. Finally, wound healing assay and transwell migration assay were performed to elucidate the effect of hub miRNA in VEC. Luciferase reporter assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to decide the role of miRNA in the expression of hub mRNA. RESULTS: Screening identified eight overlapping dysregulated genes in patients with VTE, three of which demonstrated a significantly decreased expression of miR-200a-5p. Low expression miR-200a-5p in VTE patients is confirmed by a receiver operating characteristic analysis (AUC = 0.800, P = 0.023) and binary logistic regression (OR = 0.359, 95% confidence interval: 0.605-0.995). RT-qPCR results showed that the miR-200a-5p level was decreased in hypoxia VEC (P = 0.038). MiR-200a-5p significantly promoted the migration ability of VEC. The result of Dual-luciferase reporter assay showed that cytochrome coxidase Ⅶc (COX7C) directly inhibit the miR-200a-5p expression by binding 5'UTR of miR-200a-5p (P = 0.011). CONCLUSIONS: We anticipate that the miR-200a-5p-COX7C pair might be involved in the progression of VTE. Moreover, miR-200a-5p might be a therapeutic target for VTE.

A Cys2/His2 Zinc Finger Protein Acts as a Repressor of the Green Revolution Gene SD1/OsGA20ox2 in Rice (Oryza sativa L.).

Gibberellins (GAs) play important roles in the regulation of plant growth and development. The green revolution gene SD1 encoding gibberellin 20-oxidase 2 (GA20ox2) has been widely used in modern rice breeding. However, the molecular mechanism of how SD1/OsGA20ox2 expression is regulated remains unclear. Here, we report a Cys2/His2 zinc finger protein ZFP207 acting as a transcriptional repressor of OsGA20ox2. ZFP207 was mainly accumulated in young tissues and more specifically in culm nodes. ZFP207-overexpression (ZFP207OE) plants displayed semidwarfism phenotype and small grains by modulating cell length. RNA interference of ZFP207 caused increased plant height and grain length. The application of exogenous GA3 could rescue the semidwarf phenotype of ZFP207OE rice seedlings. Moreover, ZFP207 repressed the expression of OsGA20ox2 via binding to its promoter region. Taken together, ZFP207 acts as a transcriptional repressor of SD1/OsGA20ox2 and it may play a critical role in plant growth and development in rice through the fine-tuning of GA biosynthesis .

The karyotype, genome survey, and assembly of Mud artemisia (Artemisia selengensis).

BACKGROUND: Artemisia selengensis is traditional Chinese medicine and phytochemical analysis indicated that A. selengensis contains essential oils, fatty acids and phenolic acids. The lack of reference genomic information may lead to tardiness in molecular biology research of A. selengensis. METHOD AND RESULTS: Karyotype analysis, genome survey, and genome assembly was employed to acquire information on the genome structure of A. selengensis. The chromosome number is 2n = 2x = 36, karyotype formula is 28 m + 8Sm, karyotype asymmetry coefficient is 58.8%, and karyotypes were symmetric to Stebbins' type 2A. Besides, the flow cytometry findings reported that the mean peak value of fluorescent intensity is 1,170,677, 2C DNA content is 12 pg and the genome size was estimated to be approximately 5.87 Gb. Furthermore, the genome survey generates 341,478,078 clean reads, unfortunately, after K-mer analysis, no significant peak can be observed, the heterozygosity, repetitive rate and genome size was unable to estimated. It is speculated that this phenomenon might be due to the complexity of genome structure. 37,266 contigs are preliminary assembled with Oxford Nanopore Technology (ONT) sequencing, totaling 804 Mb and GC content was 34.08%. The total length is 804,475,881 bp, N50 is 29,624 bp, and the largest contig length is 239,792 bp. CONCLUSION: This study reveals the preliminary information of genome size of A. selengensis. These findings may provide supportive information for sequencing and assembly of whole-genome sequencing and encourage the progress of functional gene discovery, genetic improvement, evolutionary study, and structural studies of A. selengensis.

In vitro human intestinal microbiota biotransformation of nobiletin using liquid chromatography-mass spectrometry analysis and background subtraction strategy.

In this study, the in vitro biotransformation of nobiletin by human intestinal microbiota, which is a bioactive polymethoxyflavone widely presented in Citrus plants, has been investigated via utilizing an anaerobic incubation protocol. The incubation samples were detected using high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. A background subtraction strategy incorporated in Microsoft Office was employed to eliminate the interferences in medium and feces. The parent and three metabolites sinensetin, 5-hydroxy-6,7,3',4'-tetramethoxyflavone, and 5-demethylnobiletin were detected and identified based on the characteristics of their protonated molecules. The proposed metabolic pathway revealed that nobiletin went through phase I metabolism including demethylation and demethoxylation in human intestinal microbiota. The characterization of nobiletin metabolic profile transformed by human intestinal bacteria would be helpful for understanding its efficacy and action mechanism.

Development and Application of a Vehicle-Mounted Soil Texture Detector.

It is of great significance to obtain soil texture information quickly for the realization of farmland management. Soil with good particle condition can well regulate the needs of plants for water, nutrients, air, and temperature during crop growth, thereby promoting high crop yields. The existing methods of measuring soil texture cannot meet the requirements of time and spatial resolution. For this reason, a vehicle-mounted soil texture detector was designed and developed based on machine vision and soil electrical conductivity devices. The detector does not require pretreatment such as air-drying and screening of the soil, and completely uses the original information of the farmland. The whole process can obtain the soil texture information in real time, omitting the complicated chemical process, and saving manpower and material resources. The vehicle-mounted detector is divided into a mechanical part, a control part, and a display part. The mechanical part provides measurement support for the acquisition of soil texture information; the control part collects and processes signals and images; the measurement results can be intuitively observed and recorded on the display, and can be operated through the mobile phone. The vehicle-mounted detector obtains soil conductivity through 4 disc electrodes, while the vehicle-mounted industrial camera captures the soil surface image, and extracts texture parameters through image processing, takes EC and texture parameters as input, and the embedded SVM model of the instrument was used to perform soil texture prediction. In order to verify the measurement accuracy of the detector, farmland verification experiments were carried out on farmland loam in Tongzhou District and Haidian District of Beijing. The R2 of the correlation between the measured value of soil EC and the actual value was 0.75, and the accuracy of soil texture prediction was 84.86%. It shows that the developed vehicle-mounted soil texture detector can meet the requirements for rapid acquisition of farmland texture information.

Assessing the utility of structure in amorphous materials.

This paper presents a set of general strategies for the analysis of structure in amorphous materials and a general approach to assessing the utility of any selected structural description. Two measures of structure are defined, "diversity" and "utility," and applied to two model glass forming binary atomic alloys, Cu50Zr50 and a Lennard-Jones A80B20 mixture. We show that the change in diversity associated with selecting Voronoi structures with high localization or low energy, while real, is too weak to support claims that specific structures are the prime cause of these local physical properties. In addition, a new structure-free measure of incipient crystal-like organization in mixtures is introduced, suitable for cases where the stable crystal is a compound structure.

Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus.

We previously mapped the type 2 diabetes mellitus-2 locus (T2dm2), which affects fasting insulin levels, to distal chromosome 19 in a leptin-deficient obese F2 intercross derived from C57BL/6 (B6) and BTBR T+ tf/J (BTBR) mice. Introgression of a 7-Mb segment of the B6 chromosome 19 into the BTBR background (strain 1339A) replicated the reduced insulin linked to T2dm2. The 1339A mice have markedly impaired insulin secretion in vivo and disrupted islet morphology. We used subcongenic strains derived from 1339A to localize the T2dm2 quantitative trait locus (QTL) to a 242-kb segment comprising the promoter, first exon and most of the first intron of the Sorcs1 gene. This was the only gene in the 1339A strain for which we detected amino acid substitutions and expression level differences between mice carrying B6 and BTBR alleles of this insert, thereby identifying variation within the Sorcs1 gene as underlying the phenotype associated with the T2dm2 locus. SorCS1 binds platelet-derived growth factor, a growth factor crucial for pericyte recruitment to the microvasculature, and may thus have a role in expanding or maintaining the islet vasculature. Our identification of the Sorcs1 gene provides insight into the pathway underlying the pathophysiology of obesity-induced type 2 diabetes mellitus.

[The Ala379Val polymorphism of platelet-activating factor acetylhydrolase gene in Chinese patients with pre-eclampsia].

OBJECTIVE: To investigate the relationship between the Ala379Val polymorphism of the platelet-activating factor acetylhydrolase gene (PAF-AH) and pre-eclampsia (PE) in Chinese pregnant women. METHODS: A total of 592 subjects (210 patients with PE and 382 healthy pregnant women) in Chengdu area were included in this study. The Ala379Val polymorphism of the PAF-AH gene was determined by PCR amplification and restriction analysis. Plasma PAF-AH and high-density lipoprotein-associated PAF-AH (H-PAF-AH) activities were measured by the trichloroacetic acid precipitation method using PAF as substrate and (3 H-acetyl) PAF as tracer. Low-density lipoprotein-associated PAF-AH (L-PAF-AH) activity was obtained by subtracting H-PAF-AH activity from plasma PAF-AH activity. RESULTS: The frequencies of the A and V alleles at Ala379Val site were 0.890 and 0.110 in the patient group, and 0.865 and 0.135 in control group, respectively. No significant differences in the frequencies of the genotypes and alleles were observed between the two groups (P>0.05). However, the body mass index (BMI) and the ratio of L-PAF-AH to H-PAF-AH activities were significantly higher, and H-PAF-AH activity was significantly lower, in patients with V alleles (AV + VV genotypes) compared to patients with AA homozygotes (P<0.05). CONCLUSION: The Ala379Val polymorphism of the PAF-AH gene was not associated with PE, but the V allele variation at this site might be associated with the increased BMI and the abnormal distribution of plasma PAF-AH activities in lipoproteins in patients with PE.

The Advancement and Application of the Single-Cell Transcriptome in Biological and Medical Research.

Single-cell RNA sequencing technology (scRNA-seq) has been steadily developing since its inception in 2009. Unlike bulk RNA-seq, scRNA-seq identifies the heterogeneity of tissue cells and reveals gene expression changes in individual cells at the microscopic level. Here, we review the development of scRNA-seq, which has gone through iterations of reverse transcription, in vitro transcription, smart-seq, drop-seq, 10 × Genomics, and spatial single-cell transcriptome technologies. The technology of 10 × Genomics has been widely applied in medicine and biology, producing rich research results. Furthermore, this review presents a summary of the analytical process for single-cell transcriptome data and its integration with other omics analyses, including genomes, epigenomes, proteomes, and metabolomics. The single-cell transcriptome has a wide range of applications in biology and medicine. This review analyzes the applications of scRNA-seq in cancer, stem cell research, developmental biology, microbiology, and other fields. In essence, scRNA-seq provides a means of elucidating gene expression patterns in single cells, thereby offering a valuable tool for scientific research. Nevertheless, the current single-cell transcriptome technology is still imperfect, and this review identifies its shortcomings and anticipates future developments. The objective of this review is to facilitate a deeper comprehension of scRNA-seq technology and its applications in biological and medical research, as well as to identify avenues for its future development in alignment with practical needs.

3D-printed Bi2Te3-based Thermoelectric Generators for Energy Harvesting and Temperature Response.

Thermoelectric generators (TEGs) are environmentally friendly energy harvesting technologies that hold great promise in the field of self-powered electronics and sensing. However, the current development of thermoelectric (TE) devices has largely lagged behind the development of thermoelectric materials, especially in the preparation of thermoelectric components with customizable shapes and excellent properties, which largely limits their practical applications. These issues can be effectively addressed by using 3D printing technology. Here, we print multiple p-type thermoelectric legs (pins) consecutively with this simple technique, and the printed TEGs have excellent thermal potential (288 µV K-1 at room temperature) and excellent temperature response properties, which exhibited an output voltage of 127.94 mV at a temperature difference (ΔT) of 40 K. The 3D-printed thermoelectric generator enables the collection of thermal energy. In addition, the device has excellent temperature sensing characteristics, and this temperature signal to electrical signal conversion is very rapid, which enables temperature sensing alarms in a wide temperature domain. Combining these features, an energy harvesting and electrical alarm concept for home-scale applications is proposed, which is expected to provide a diverse research idea for the application of next-generation thermoelectric devices.

Characterization of a vacuolar zinc transporter OZT1 in rice (Oryza sativa L.).

The CDF family is a ubiquitous family that has been identified in prokaryotes, eukaryotes, and archaea. Members of this family are important heavy metal transporters that transport metal ions out of the cytoplasm. In this research, a full length cDNA named Oryza sativa Zn Transporter 1 (OZT1) that closely related to rat ZnT-2 (Zn Transporter 2) gene was isolated from rice. The OZT1 encoding a CDF family protein shares 28.2 % ~ 84.3 % of identities and 49.3 % ~ 90.9 % of similarities with other zinc transporters such as RnZnT-2, HsZnT-8, RnZnT-8 and AtMTP1. OZT1 was constitutively expressed in various rice tissues. The OZT1 expression was significantly induced both in the seedlings of japonica rice Nipponbare and indica rice IR26 in response to Zn(2+) and Cd(2+) treatments. Besides, OZT1 expression was also increased when exposed to other excess metals, such as Cu(2+), Fe(2+) and Mg(2+). Subcellular localization analysis indicated that OZT1 localized to vacuole. Heterologous expression of OZT1 in yeast increased tolerance to Zn(2+) and Cd(2+) stress but not the Mg(2+) stress. Together, OZT1 is a CDF family vacuolar zinc transporter conferring tolerance to Zn(2+) and Cd(2+) stress, which is important to transporting and homeostasis of Zn, Cd or other heavy metals in plants.

Prevention of allergic airway hyperresponsiveness and remodeling in mice by Astragaliradix antiasthmatic decoction.

BACKGROUND: Astragali radix Antiasthmatic Decoction (AAD), a traditional Chinese medication, is found effective in treating allergic diseases and chronic cough. The purpose of this study is to determine whether this medication could suppress allergen-induced airway hyperresponsiveness (AHR) and remodeling in mice, and its possible mechanisms. METHODS: A mouse model of chronic asthma was used to investigate the effects of AAD on the airway lesions. Mice were sensitized and challenged with ovalbumin (OVA), and the extent of AHR and airway remodeling were characterized. Cells and cytokines in the bronchoalveolar lavage fluid (BALF) were examined. RESULTS: AAD treatment effectively decreased OVA-induced AHR, eosinophilic airway inflammation, and collagen deposition around the airway. It significantly reduced the levels of IL-13 and TGF-ß1, but exerted inconsiderable effect on INF-γ and IL-10. CONCLUSIONS: AAD greatly improves the symptoms of allergic airway remodeling probably through inhibition of Th2 cytokines and TGF-ß1.

Comparison of seven complete mitochondrial genomes from Lamprologus and Neolamprologus (Chordata, Teleostei, Perciformes) and the phylogenetic implications for Cichlidae.

In this study, mitochondrial genomes (mitogenomes) of seven cichlid species (Lamprologuskungweensis, L.meleagris, L.ornatipinnis, Neolamprologusbrevis, N.caudopunctatus, N.leleupi, and N.similis) are characterized for the first time. The newly sequenced mitogenomes contained 37 typical genes [13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs) and 22 transfer RNA genes (tRNAs)]. The mitogenomes were 16,562 ~ 16,587 bp in length with an A + T composition of 52.1~58.8%. The cichlid mitogenomes had a comparable nucleotide composition, A + T content was higher than the G + C content. The AT-skews of most mitogenomes were inconspicuously positive and the GC-skews were negative, indicating higher occurrences of C than G. Most PCGs started with the conventional start codon, ATN. There was no essential difference in the codon usage patterns of these seven species. Using Ka/Ks, we found the fastest-evolving gene were atp8. But the results of p-distance indicated that the fastest-evolving gene was nad6. Phylogenetic analysis revealed that L.meleagris did not cluster with Lamprologus species, but with species from the genus Neolamprologus. The novel information obtained about these mitogenomes will contribute to elucidating the complex relationships among cichlid species.

Safety outcomes of salbutamol: A systematic review and meta-analysis.

PURPOSE: Salbutamol has been used to alleviate bronchospasm in airway disease for decades, while its potential risks have not been systematically investigated yet. The risk of any potential adverse events (AEs) in patients treated with salbutamol was assessed through systematic review and meta-analysis. METHODS: A systematic search of the literature was conducted, using EMBASE, PubMed and Cochrane library, until 3 April 2023. Once the AE incidence was evaluated, randomized controlled trials (RCTs) were eligible for review. The endpoints included the incidence of total AEs, severe AEs, treatment discontinuation and specific AEs. The pooled AEs incidence was analysed via random-effects model in a single-arm meta-analysis. A subgroup study was carried out to examine whether the pooled incidence of AE differed by indications or formulations. RESULTS: Of the 8912 studies that were identified, 58 RCTs met the inclusion criteria and involved 12 961 participants. The analysis showed the pooled incidences of total AEs, severe AEs and treatment discontinuation in patients treated with salbutamol were 34%, 2% and 3%, respectively. Subgroup analysis indicated that premature labour users and intravenous salbutamol users were more likely associated with total AEs. The most frequently observed specific AEs were palpitations or tachycardia. CONCLUSION: This meta-analysis indicated that salbutamol was associated with a very common risk of palpitations or tachycardia. Clinical vigilance and research efforts are needed to optimize the safe use of salbutamol.

Molecular Characterization and Phylogenetic Analysis of Casein Gene Family in Camelus ferus.

Camel milk is known for its exceptional medical uses. It has been used since ancient times to treat infant diarrhea, hepatitis, insulin-dependent diabetes (IDDM), lactose intolerance, alcohol-induced liver damage, allergies, and autism. It has the power to treat several diseases, with cancer being the most significant. This study investigated the evolutionary relationship, physiochemical characteristics, and comparative genomic analysis of the casein gene family (CSN1S1, CSN2, CSN1S2, and CSN3) in Camelus ferus. Molecular phylogenetics showing the camelid species clustered casein nucleotide sequences into four groups: CSN1S1, CSN2, CSN1S2, and CSN3. The casein proteins from camels were evaluated and found to be unstable, thermostable, and hydrophilic. CSN1S2, CSN2, and CSN3 were acidic, but CSN1S1 was basic. CSN1S1 showed positive selection for one amino acid (Q), CSN1S2 and CSN2 for three (T, K, Q), and CSN3 showed no positive selection. We also compared high-milk-output species such as cattle (Bos Tarus) and low-milk-yield species such as sheep (Ovies Aries) with camels (Camel ferus) and discovered that YY1 sites are more frequent in sheep than in camels and very low in cattle. We concluded that the ratio of YY1 sites in these species may affect milk production.

Molecular cytogenetic map visualizes the heterozygotic genome and identifies translocation chromosomes in Citrus sinensis.

Citrus sinensis is the most cultivated and economically valuable Citrus species in the world, whose genome has been assembled by three generation sequencings. However, chromosome recognition remains a problem due to the small size of chromosomes, and difficulty in differentiating between pseudo and real chromosomes because of a highly heterozygous genome. Here, we employ fluorescence in situ hybridization (FISH) with 9 chromosome painting probes, 30 oligo pools, and 8 repetitive sequences to visualize 18 chromosomes. Then, we develop an approach to identify each chromosome in one cell through single experiment of oligo-FISH and Chromoycin A3 (CMA) staining. By this approach, we construct a high-resolution molecular cytogenetic map containing the physical positions of CMA banding and 38 sequences of FISH including centromere regions, which enables us to visualize significant differences between homologous chromosomes. Based on the map, we locate several highly repetitive sequences on chromosomes and estimate sizes and copy numbers of each site. In particular, we discover the translocation regions of chromosomes 4 and 9 in C. sinensis "Valencia." The high-resolution molecular cytogenetic map will help improve understanding of sweet orange genome assembly and also provide a fundamental reference for investigating chromosome evolution and chromosome engineering for genetic improvement in Citrus.

The Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cognition in Patients With Traumatic Brain Injury: A Protocol for a Randomized Controlled Trial.

Cognitive impairment, defined as a decline in memory and executive function, is one of the most severe complications of traumatic brain injury (TBI). Patients with TBI are often unable to return to work due to cognitive impairment and their overall quality of life is reduced. TBI can bring a serious economic burden to patient's families and to society. Reported findings on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving cognitive impairment following TBI are inconsistent. The purpose of the proposed study is to investigate whether rTMS can improve memory and executive function in patients with TBI. Herein, we propose a prospective randomized placebo-controlled (rTMS, sham rTMS, cognitive training), parallel-group, single-center trial. 36 participants with a TBI occurring at least 6 months prior will be recruited from an inpatient rehabilitation center. Participants will be randomly assigned to the real rTMS, sham rTMS, or cognitive training groups with a ratio of 1:1:1. A 20-session transcranial magnetic stimulation protocol will be applied to the left and right dorsolateral prefrontal cortices (DLPFC) at frequencies of 10 Hz and 1 Hz, respectively. Neuropsychological assessments will be performed at four time points: baseline, after the 10th rTMS session, after the 20th rTMS session, and 30 days post-intervention. The primary outcome is change in executive function assessed using the Shape Trail Test (STT). The secondary outcome measures are measures from neuropsychological tests: the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory Test (BVMT), the Digit Span Test (DST). We report on positive preliminary results in terms of improving memory and executive function as well as beneficial changes in brain connectivity among TBI patients undergoing rTMS and hypothesize that we will obtain similar results in the proposed study.

Spiradiclisliboensis (Rubiaceae), a new species from limestone mountain areas in Guizhou, China.

Spiradiclisliboensis L. Wu & W. J. Liu, a new species in tribe Ophiorrhizeae of Rubiaceae from limestone mountain areas of Guizhou, south-western China, is described and illustrated. It is similar to S.guangdongensis and S.jingxiensis, but differs from the latter two by the following traits: stipule triangular, inflorescence sessile or with peduncle up to 0.5 mm long, pedicel 0.8-2.2 mm long, corolla white, salverform, corolla tube 1.6-2.2 cm long, corolla tube of long-styled morph inside with a villous ring and stigmas positioned at the throat of the corolla tube. The conservation status is assessed as "Vulnerable" (VU) according to the IUCN Red List Categories and Criteria.

Humic Acids Inhibit Platelet Activation to Reduce Venous Thromboembolism in Mice.

Objective: We aimed to investigate the effects of the natural product humic acids (HA) on platelet activation and development of venous thromboembolism (VTE) in mice and further explore the relevant mechanism. Methods: Eight-week C57BL/6 mice were randomly assigned to three groups: sham operation group (n = 7), VTE group (n = 8), and VTE + HA group (n = 10). Thrombi were harvested to hematoxylin-eosin staining to evaluate the thrombolysis and recanalization of the thrombus. In addition, flow cytometry was performed to detect the expression levels of protein disulfide isomerase on endothelial-derived exosomes and glycoprotein IIb/IIIa on the surface of the activated platelets surface in plasma. Furthermore, the protein expression level of glycoprotein IIb/IIIa in thrombus was determined by immunohistochemistry and immunofluorescence. Results: The length of thrombosis in the VTE + HA group was significantly shorter than that in the VTE group (P = 0.040). No significant differences were observed in thrombolysis and recanalization between the VTE + HA group and the VTE group (P > 0.05). The content of protein disulfide isomerase carried by endothelial-derived exosomes was significantly increased in the VTE group (P = 0.008) but significantly reduced by native humic acids (P = 0.012). Compared with the VTE group, the expression of glycoprotein IIb/IIIa on activated platelet surface in the VTE + HA group was significantly decreased (P = 0.002). The concentration of plasmatic P-selectin in the VTE group was significantly higher than that in the VTE + HA group (P < 0.001). Conclusion: We demonstrate that HA possess a pharmacological property that decreases venous thrombus formation in mice. The underlying mechanism is that HA could inhibit the expression of glycoprotein IIb/IIIa on the activated platelets surface by suppressing endothelial-derived exosomes carrying on protein disulfide isomerase, thereby blocking platelet activation.