Full-length transcriptome profiling of Acanthopanax gracilistylus provides new insight into the kaurenoic acid biosynthesis pathway.

Acanthopanax gracilistylus is a deciduous plant in the family Araliaceae, which is commonly used in Chinese herbal medicine, as the root bark has functions of nourishing the liver and kidneys, removing dampness and expelling wind, and strengthening the bones and tendons. Kaurenoic acid (KA) is the main effective substance in the root bark of A. gracilistylus with strong anti-inflammatory effects. To elucidate the KA biosynthesis pathway, second-generation (DNA nanoball) and third-generation (Pacific Biosciences) sequencing were performed to analyze the transcriptomes of the A. gracilistylus leaves, roots, and stems. Among the total 505,880 isoforms, 408,954 were annotated by seven major databases. Sixty isoforms with complete open reading frames encoding 11 key enzymes involved in the KA biosynthesis pathway were identified. Correlation analysis between isoform expression and KA content identified a total of eight key genes. Six key enzyme genes involved in KA biosynthesis were validated by real-time quantitative polymerase chain reaction. Based on the sequence analysis, the spatial structure of ent-kaurene oxidase was modeled, which plays roles in the three continuous oxidations steps of KA biosynthesis. This study greatly enriches the transcriptome data of A. gracilistylus and facilitates further analysis of the function and regulation mechanism of key enzymes in the KA biosynthesis pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01436-7.

The value of a panel of circulating microRNAs in screening prostate cancer.

Background: Prostate cancer (PCa) remains a worldwide public health problem that poses a serious threat to the health of men worldwide. Many studies have found that microRNA (miRNA) in serum has the potential to be a biomarker for cancer screening. Our study was conducted to investigate the value of serum miRNAs in PCa screening. Methods: We selected 12 miRNAs from past studies for its association with PCa. We checked the expression levels of these miRNAs in the serum of 112 PCa patients and 112 healthy controls in a two-stage experiment. We plotted the receiver operating characteristic curve of miRNAs in the validation stage and constructed a four-miRNA panel with the highest diagnostic value using stepwise logistic regression. We also predicted the target genes with these four miRNAs through online databases and performed Gene Ontology functional annotation and pathway analysis. Results: The results showed that six miRNAs (miR-429, miR-10a-5p, miR-183-5p, miR-181a-5p, miR-1231, miR-129-5p) were abnormally expressed in the serum of PCa patients. We used four of these miRNAs including miR-1231, miR-10a-5p, miR-429 and miR-129-5p to construct a combination of miRNAs with high specificity and sensitivity in screening PCa (area under the curve =0.878). Bioinformatics analysis showed that the genes targeted by these miRNAs can be linked to the development of PCa. Conclusions: Our study detected and identified a set of miRNAs that serves as screening marker for PCa, which may assist in early diagnosis and treatment of PCa.

Exosomes derived from diabetic serum accelerate the progression of osteoarthritis.

Diabetes mellitus (DM) has been demonstrated to accelerate the progression of osteoarthritis (OA) by largely unknown mechanisms. Studies have shown that DM dysfunctional adipocyte-derived exosomes play a crucial role in the pathogenesis of remote organ functions. The present study aimed to clarify whether and how diabetic adipocyte-derived exosomes mediate the pathological regulation of OA. We found that intraarticular injection of DM serum exosomes in the non-diabetic mice significantly exacerbated OA injury as evidenced by a rough and fractured cartilage surface as well as increased chondrocyte apoptosis, decreased mitochondrial membrane potential (△Ψ) and increased expression of cleaved caspase-3. Mechanistic investigation identified that miR-130b-3p was significantly increased in circulating exosomes derived from DM mice and exosomes derived from HG-treated normal adipocytes, and we demonstrated that transfection of miR-130b-3p mimics significantly exacerbated the mitochondrial function of chondrocytes. Our data also indicated that miR-130b-3p impaired the △Ψ, increased cleaved caspase-3 levels, and decreased the expression of 5'-adenosine monophosphate-activated protein kinase α1 (AMPKα1), Silent mating-type information regulation 2 homolog 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in chondrocytes. Pharmacologic activation of AMPKα1 using AICAR reversed the â–³Ψ and catabolic responses in chondrocytes transfected with miR-130b-3p mimics. Moreover, AICAR decreased the effects of miR-130b-3p mimics on chondrocytes transfected with SIRT1-siRNA or PGC-1α-siRNA. The current study demonstrated that adipocyte-derived exosomal miR-130b-3p under DM conditions suppresses mitochondrial function in chondrocytes through targeting the AMPKα1/SIRT1/PGC1-α pathway, thus exacerbating OA injury.

The ecological suitability area of Cirsium lineare (Thunb.) Sch.-Bip. under future climate change in China based on MaxEnt modeling.

Many kinds of medicinal ingredients occur in Cirsium lineare that have good clinical efficacy, conferring on this species its high medicinal development value. However, with a rapidly changing global climate, it is increasingly imperative to study the factors affecting the habitat distribution and survival of species. We predicted the current and future distribution areas of suitable habitats for C. lineare, analyzed the importance of environmental variables in influencing habitat shifts, and described the alterations to suitable habitats of C. lineare in different periods (modern, 2050s, and 2070s) and scenarios (RCP2.6, RCP4.5, and RCP8.5). The results show that, under the current climate, the total suitable area of C. lineare is about 2,220,900 km2, of which the highly suitable portion amounts to ca. 292,600 km2. The minimum temperature of the coldest month, annual precipitation, and mean daily temperature range are the chief environmental variables affecting the distribution of habitat for C. lineare. In the same period, with rising greenhouse gas emission concentrations, the total suitable area will increase. In general, under future climate change, the suitable habitat for C. lineare will gradually migrate to the west and north, and its total suitable area will also expand. The results of this experiment can be used for the conservation and management of the wild resources of C. lineare. We can choose suitable growth areas to protect the medicinal resources of C. lineare through in situ conservation and artificial breeding.

Asymmetric Extrusion Technology of Mg Alloy: A Review.

Magnesium (Mg) alloy is a widely used lightweight metal structural material due to its high specific strength and stiffness, excellent damping performance, and recyclability. Wrought Mg alloys are particularly favored in fields such as aerospace, transportation, and biomedical stents. However, most wrought Mg alloys with a hexagonal close-packed (HCP) crystal structure lack sufficient independent slip systems to meet the von Mises criterion for uniform plastic deformation at room temperature. This can result in the formation of a strong basal texture during plastic deformation and poor room temperature plastic formability. Enhancing the room temperature forming performance is therefore a crucial challenge that needs to be addressed in order to expand the application of Mg alloy sheets. Our research group has comprehensively summarized significant work and the latest research progress in improving the room temperature forming of Mg alloy sheets via extrusion technology in recent years. Specifically, we have developed a new type of asymmetric extrusion technology that combines material structure evolution, mechanical properties, and forming behavior analysis. We have elucidated the extrusion process characteristics, texture control mechanism, and forming properties of Mg alloy sheets through plastic deformation mechanisms, mold design, and finite element numerical simulation. The findings of our study present an innovative extrusion technology for the fabrication of highly formable Mg alloy sheets, which can be utilized in various applications.

PagDA1a and PagDA1b expression improves salt and drought resistance in transgenic poplar through regulating ion homeostasis and reactive oxygen species scavenging.

DA1/DAR proteins play a crucial role in plant biomass production. However, their functions in woody plants in response to abiotic stress are still unknown. In this study, a total number of six PagDA1/DAR family genes were identified in the poplar genome, and the biological functions of PagDA1a and PagDA1b in the resistance to salt and drought stresses were investigated in transgenic poplar. PagDA1a and PagDA1b were ubiquitously expressed in roots, stems, and leaves, with predominant expression in roots, and were significantly induced by abiotic stress and ABA. Transgenic poplar overexpressing either PagDA1a or PagDA1b showed restrained growth but improved resistance to salt and drought stresses. Further ion content and antioxidant enzyme expression analyses exhibited that transgenic poplar accumulated less sodium (Na+), hydrogen peroxide (H2O2) and malondialdehyde (MDA) in the leaves, accompanied with increased activity of superoxide dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT), and up-regulated transcription of SOD1, APX1, and CAT2. Our observations demonstrate that PagDA1a and PagDA1b improve salt and drought tolerance through ion homeostasis optimization and ROS scavenging ability enhancement in transgenic poplar, and both can be used for the future genetic breeding of new salt and drought tolerant tree species.

Improving the Mechanical Properties of Mg-5Al-2Ca-1Mn-0.5Zn Alloy through Rotary Swaging.

To meet the demand for more extensive applications of Mg alloys, a Mg-5Al-2Ca-1Mn-0.5Zn alloy without RE was prepared in this paper, and its mechanical properties were further improved by conventional hot extrusion and subsequent rotary swaging. The results show that the hardness of the alloy decreases along the radial central region after rotary swaging. The strength and hardness of the central area are lower, but the ductility is higher. The yield strength and ultimate tensile strength of the alloy in the peripheral area after rotary swaging reach 352 MPa and 386 MPa, respectively, while the elongation remains at 9.6%, exhibiting better strength-ductility synergy. The grain refinement and dislocation increase caused by rotary swaging promoted strength improvement. The activation of non-basal slips during rotary swaging is an important reason for the alloy to maintain good plasticity while improving strength.

Comparative Genomic Analysis of a Methylorubrum rhodesianum MB200 Isolated from Biogas Digesters Provided New Insights into the Carbon Metabolism of Methylotrophic Bacteria.

Methylotrophic bacteria are widely distributed in nature and can be applied in bioconversion because of their ability to use one-carbon source. The aim of this study was to investigate the mechanism underlying utilization of high methanol content and other carbon sources by Methylorubrum rhodesianum strain MB200 via comparative genomics and analysis of carbon metabolism pathway. The genomic analysis revealed that the strain MB200 had a genome size of 5.7 Mb and two plasmids. Its genome was presented and compared with that of the 25 fully sequenced strains of Methylobacterium genus. Comparative genomics revealed that the Methylorubrum strains had closer collinearity, more shared orthogroups, and more conservative MDH cluster. The transcriptome analysis of the strain MB200 in the presence of various carbon sources revealed that a battery of genes was involved in the methanol metabolism. These genes are involved in the following functions: carbon fixation, electron transfer chain, ATP energy release, and resistance to oxidation. Particularly, the central carbon metabolism pathway of the strain MB200 was reconstructed to reflect the possible reality of the carbon metabolism, including ethanol metabolism. Partial propionate metabolism involved in ethyl malonyl-CoA (EMC) pathway might help to relieve the restriction of the serine cycle. In addition, the glycine cleavage system (GCS) was observed to participate in the central carbon metabolism pathway. The study revealed the coordination of several metabolic pathways, where various carbon sources could induce associated metabolic pathways. To the best of our knowledge, this is the first study providing a more comprehensive understanding of the central carbon metabolism in Methylorubrum. This study provided a reference for potential synthetic and industrial applications of this genus and its use as chassis cells.

IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis.

Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.

Genome-wide identification of the AlkB homologs gene family, PagALKBH9B and PagALKBH10B regulated salt stress response in Populus.

The AlkB homologs (ALKBH) gene family regulates N6-methyladenosine (m6A) RNA methylation and is involved in plant growth and the abiotic stress response. Poplar is an important model plant for studying perennial woody plants. Poplars typically have a long juvenile period of 7-10 years, requiring long periods of time for studies of flowering or mature wood properties. Consequently, functional studies of the ALKBH genes in Populus species have been limited. Based on AtALKBHs sequence similarity with Arabidopsis thaliana, 23 PagALKBHs were identified in the genome of the poplar 84K hybrid genotype (P. alba × P. tremula var. glandulosa), and gene structures and conserved domains were confirmed between homologs. The PagALKBH proteins were classified into six groups based on conserved sequence compared with human, Arabidopsis, maize, rice, wheat, tomato, barley, and grape. All homologs of PagALKBHs were tissue-specific; most were highly expressed in leaves. ALKBH9B and ALKBH10B are m6A demethylases and overexpression of their homologs PagALKBH9B and PagALKBH10B reduced m6A RNA methylation in transgenic lines. The number of adventitious roots and the biomass accumulation of transgenic lines decreased compared with WT. Therefore, PagALKBH9B and PagALKBH10B mediate m6A RNA demethylation and play a regulatory role in poplar growth and development. Overexpression of PagALKBH9B and PagALKBH10B can reduce the accumulation of H2O2 and oxidative damage by increasing the activities of SOD, POD, and CAT, and enhancing protection for Chl a/b, thereby increasing the salt tolerance of transgenic lines. However, overexpression lines were more sensitive to drought stress due to reduced proline content. This research revealed comprehensive information about the PagALKBH gene family and their roles in growth and development and responsing to salt stress of poplar.

Single-Crystalline Pyramidal TiCx Particles Grown by Biphase Diffusion Synthesis.

In this study, we present single-crystalline pyramid-shaped (SP) TiCx particles synthesized on a stacked melt (copper)-solid (titanium) substrate using a biphase diffusion synthesis (BDS) method, in which different sizes ranging from nano- to micrometer scale were obtained within the copper melt with the {100} planes exposed to air. Direct observation and further plasma treatment of the pyramids at different self-assembly stages facilitated the investigation of their growth mode, especially in the horizontal plane. The dendritic growth mode along with the edge and corner-shared modes of the SP TiCx particles frozen on the copper surface was investigated. With SP TiCx particles stacked on top, MoS2-based phototransistors exhibited an up to 6-fold photocurrent increase under laser illumination at different wavelengths, which was attributed to the localized surface plasmonic resonance (LSPR) effect. The BDS method is applied for the synthesis of SP TiCx particles, with a detailed investigation of the relevant growth mode and related applications, such as decoration for high-performance photodevices.

Blood-brain barrier-penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy.

We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shell incorporating a dual-action ligand that facilitates BBB penetration, tumor cell targeting, and Cas9/sgRNA selective release. Our encapsulating nanocapsules evidenced promising glioblastoma tissue targeting that led to high PLK1 gene editing efficiency in a brain tumor (up to 38.1%) with negligible (less than 0.5%) off-target gene editing in high-risk tissues. Treatment with nanocapsules extended median survival time (68 days versus 24 days in nonfunctional sgRNA-treated mice). Our new CRISPR-Cas9 delivery system thus addresses various delivery challenges to demonstrate safe and tumor-specific delivery of gene editing Cas9 ribonucleoprotein for improved glioblastoma treatment that may potentially be therapeutically useful in other brain diseases.

Transcriptome analyses reveal the expression profile of genes related to lignan biosynthesis in Anthriscus sylvestris L. Hoffm. Gen.

Anthriscus sylvestris L. Hoffm. Gen (A. sylvestris) is a perennial herb widely used for antitussive and diuretic purposes in traditional Korean and Chinese medicine. Lignans are critical secondary metabolites with widely pharmacological activities in A. sylvestris. Using transcriptome data of A. sylvestris, we identified genes related to lignan biosynthesis. In all, 123,852 unigenes were obtained from the flowers, leaves, roots, and stems of A. sylvestris with the Illumina HiSeq 4000 platform. The average length of unigenes was 1,123 bp and 91,217 (73.65%) of them were annotated in public databases. Differentially expressed genes and root-specific genes were analyzed between roots and the other three tissue types by comparing gene expression profiles. Specifically, the key enzyme genes involved in lignan biosynthesis were identified and analyzed. The expression levels of some of these genes were highest in the roots, consistent with the accumulation of deoxypodophyllotoxin. These expression levels were experimentally verified via quantitative real-time polymerase chain reaction (qRT-PCR). This research provides valuable information on the transcriptome data of A. sylvestris and the identification of candidate genes associated with the biosynthesis of lignans, laying the foundation for further research on genomics in A. sylvestris and related species. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01156-w.

Advanced Glycation End Products Induced Mitochondrial Dysfunction of Chondrocytes through Repression of AMPKα-SIRT1-PGC-1α Pathway.

INTRODUCTION: Our previous studies have demonstrated advanced glycation end products (AGEs) was an important mediator in osteoarthritis (OA) which may induce mitochondrial dysfunction. AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and its downstream target peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) are the critical sensors that regulate mitochondrial biogenesis and have been recognized as therapeutic targets in OA. This study was designed to test whether AGEs caused mitochondrial dysfunction through modulation of AMPKα/SIRT1/PGC-1α. METHODS: We knocked down or overexpressed AMPKα, SIRT1, and PGC-1α by small interfering RNA or plasmid DNA transfection, respectively. Mitochondrial membrane potential (△Ψ) was detected by tetraethylbenzimidazolyl carbocyanine iodide (JC-1) fluorescence probe. RESULTS: The results showed that AGEs impaired △Ψ, intracellular ATP level, and mitochondrial DNA content, linked to decreased AMPKα, SIRT1, and PGC-1α expression in chondrocyte. AMPKα pharmacologic activation or overexpression of AMPKα, SIRT1, and PGC-1α reversed impairments of mitochondrial biogenesis, oxidative stress, and inflammation in AGEs-induced chondrocytes. However, AMPKα activation using AICAR had decreased capacity to increase each of those same effect readouts in AGEs-treated SIRT1-siRNA or PGC-1α-siRNA chondrocyte. CONCLUSION: Taken together, AGEs reduced the AMPKα/SIRT1/PGC-1α signaling in chondrocytes, leading to mitochondrial dysfunction as a result of increased oxidative stress, inflammation, and apoptosis. These results indicated that target AMPK may be as a novel therapeutic strategy for AGEs-related OA prevention.

Heme Oxygenase-1 targeting exosomes for temozolomide resistant glioblastoma synergistic therapy.

Glioblastoma (GBM) is a highly fatal and recurrent brain cancer without a complete prevailing remedy. Although the synthetic nanotechnology-based approaches exhibit excellent therapeutic potential, the associated cytotoxic effects and organ clearance failure rest major obstacles from bench to clinics. Here, we explored allogeneic bone marrow mesenchymal stem cells isolated exosomes (BMSCExo) decorated with heme oxygenase-1 (HMOX1) specific short peptide (HSSP) as temozolomide (TMZ) and small interfering RNA (siRNA) nanocarrier for TMZ resistant glioblastoma therapy. The BMSCExo had excellent TMZ and siRNA loading ability and could traverse the blood-brain barrier (BBB) by leveraging its intrinsic brain accumulation property. Notably, with HSSP decoration, the TMZ or siRNA encapsulated BMSCExo exhibited excellent TMZ resistant GBM targeting ability both in vitro and in vivo due to the overexpression of HMOX1 in TMZ resistant GBM cells. Further, the HSSP decorated BMSCExo delivered the STAT3 targeted siRNA to the TMZ resistant glioma and restore the TMZ sensitivity, consequently achieved the synergistically drug resistant GBM treatment with TMZ. Our results showed this biomimetic nanoplatform can serve as a flexible, robust and inert system for GBM treatment, especially emphasizing the drug resistant challenge.

Cation-Free siRNA Micelles as Effective Drug Delivery Platform and Potent RNAi Nanomedicines for Glioblastoma Therapy.

Nanoparticle-based small interfering RNA (siRNA) therapy shows great promise for glioblastoma (GBM). However, charge associated toxicity and limited blood-brain-barrier (BBB) penetration remain significant challenges for siRNA delivery for GBM therapy. Herein, novel cation-free siRNA micelles, prepared by the self-assembly of siRNA-disulfide-poly(N-isopropylacrylamide) (siRNA-SS-PNIPAM) diblock copolymers, are prepared. The siRNA micelles not only display enhanced blood circulation time, superior cell take-up, and effective at-site siRNA release, but also achieve potent BBB penetration. Moreover, due to being non-cationic, these siRNA micelles exert no charge-associated toxicity. Notably, these desirable properties of this novel RNA interfering (RNAi) nanomedicine result in outstanding growth inhibition of orthotopic U87MG xenografts without causing adverse effects, achieving remarkably improved survival benefits. Moreover, as a novel type of polymeric micelle, the siRNA micelle displays effective drug loading ability. When utilizing temozolomide (TMZ) as a model loading drug, the siRNA micelle realizes effective synergistic therapy effect via targeting the key gene (signal transducers and activators of transcription 3, STAT3) in TMZ drug resistant pathways. The authors' results show that this siRNA micelle nanoparticle can serve as a robust and versatile drug codelivery platform, and RNAi nanomedicine and for effective GBM treatment.

Polymeric Nanoparticles for Mitochondria Targeting Mediated Robust Cancer Therapy.

Despite all sorts of innovations in medical researches over the past decades, cancer remains a major threat to human health. Mitochondria are essential organelles in eukaryotic cells, and their dysfunctions contribute to numerous diseases including cancers. Mitochondria-targeted cancer therapy, which specifically delivers drugs into the mitochondria, is a promising strategy for enhancing anticancer treatment efficiency. However, owing to their special double-layered membrane system and highly negative potentials, mitochondria remain a challenging target for therapeutic agents to reach and access. Polymeric nanoparticles exceed in cancer therapy ascribed to their unique features including ideal biocompatibility, readily design and synthesis, as well as flexible ligand decoration. Significant efforts have been put forward to develop mitochondria-targeted polymeric nanoparticles. In this review, we focused on the smart design of polymeric nanosystems for mitochondria targeting and summarized the current applications in improving cancer therapy.

Murine pharmacokinetics and antimalarial pharmacodynamics of dihydroartemisinin trimer self-assembled nanoparticles.

Currently, conjugation of artemisinin-derived dimers, trimers, and tetramers is a viable strategy for developing new effective antimalarial candidates. Furthermore, nanotechnology is an effective means to achieve intravenous administration of hydrophobic drugs. In this paper, an ester-linked dihydroartemisinin trimer (DHA3) was synthesized and further prepared as self-assembled nanoparticles (DHA3NPs) by a one-step nanoprecipitation method. The pharmacokinetics and antimalarial pharmacodynamics of DHA3NPs were studied in rats and mice infected with Plasmodium yoelii BY265 (PyBY265). DHA3NPs had a regular spherical shape with a uniform size distribution of 140.27 ± 3.59 nm, entrapment efficiency (EE) of 99.63 ± 0.17%, and drug loading efficiency (DL) of 79.62 ± 0.11%. The in vitro release characterization revealed that DHA3NPs were easily hydrolysed into DHA in an esterase environment. The pharmacokinetics study demonstrated that the area under the concentration-time curve (AUC0-t) of DHA in DHA3NPs group was 2070.52 ± 578.76 h×ng×mL-1, which was higher than that of DHA and artesunate (AS) control groups (AUC0-t values of 724.18 ± 94.32 and 448.40 ± 94.45 h×ng×mL-1, respectively) (P < 0.05). The antimalarial pharmacodynamics in vivo suggested that DHA3NPS (ED90 7.82 ± 1.16 µmol×(kg×day)-1) had a superior antimalarial effect compared with that of control groups (ED90 values of 14.68 ± 0.98 (DHA) and 14.34 ± 1.96 (AS) µmol×(kg×day)-1) (P < 0.05). In addition, DHA3NPS reduced the recurrence ratio and improved the cure ratio and survival time. In summary, DHA3NPs exhibited promising pharmacokinetic characteristics and antimalarial pharmacodynamics in vivo.

Role of microRNAs in intervertebral disc degeneration (Review).

The incidence of lower back pain caused by intervertebral disc degeneration (IDD) is gradually increasing. IDD not only affects the quality of life of the patients, but also poses a major socioeconomic burden. There is currently no optimal method for delaying or reversing IDD, mainly due to its unknown pathogenesis. MicroRNAs (miRNAs/miRs) participate in the development of a number of diseases, including IDD. Abnormal expression of miRNAs in the intervertebral disc is implicated in various pathological processes underlying the development of IDD, including nucleus pulposus (NP) cell (NPC) proliferation, NPC apoptosis, extracellular matrix remodeling, inflammation and cartilaginous endplate changes, among others. The focus of the present review was the advances in research on the involvement of miRNAs in the mechanism underlying IDD. Further research is expected to identify markers for early diagnosis of IDD and new targets for delaying or reversing IDD.

Identify of Fast-Growing Related Genes Especially in Height Growth by Combining QTL Analysis and Transcriptome in Salix matsudana (Koidz).

The study on the fast-growing traits of trees, mainly valued by tree height (TH) and diameter at breast height (DBH), is of great significance to promote the development of the forest industry. Quantitative trait locus (QTL) mapping based on high-density genetic maps is an efficient approach to identify genetic regions for fast-growing traits. In our study, a high-density genetic map for the F1 population was constructed. The genetic map had a total size of 5,484.07 centimorgan (cM), containing 5,956 single nucleotide polymorphisms (SNPs) based on Specific Length Amplified Fragment sequencing. Six fast-growing related stable QTL were identified on six chromosomes, and five stable QTL were identified by a principal component analysis (PCA). By combining the RNA-seq analysis for the two parents and two progenies with the qRT-PCR analysis, four candidate genes, annotated as DnaJ, 1-aminocyclopropane-1-carboxylate oxidase 1 (ACO1), Caffeic acid 3-O-methyltransferase 1 (COMT1), and Dirigent protein 6 (DIR6), that may regulate height growth were identified. Several lignin biosynthesis-related genes that may take part in height growth were detected. In addition, 21 hotspots in this population were found. The results of this study will provide an important foundation for further studies on the molecular and genetic regulation of TH and DBH.