Bulked Segregant Analysis and Association Analysis Identified the Polymorphisms Related to the Intermuscular Bones in Common Carp (Cyprinus carpio).

The allotetraploid common carp is one of the most important freshwater food fish. However, the IBs found in allotetraploid common carp increase the difficulty in fish meat processing and consumption. Although candidate genes associated with the total IB number have been identified, the SNPs associated with the numbers of the total IBs and different forms of IBs have not yet been identified, hindering the breeding of IB-reduced common carp. Herein, the numbers of different types of IBs in three common carp strains were measured. Using whole-genome resequencing and bulked segregant analysis in three pairs of IB-more and IB-less groups, we identified the consensus nonsynonymous SNPs in three strains of common carp. Screening the flanking regions of these SNPs led to the detection of other SNPs. Association study detected 21 SNPs significantly associated with the number of total IBs, epineural-IBs, and ten detailed types of IBs. We observed the joint effects of multiple SNPs on each associated IB number with an improved explained percentage of phenotypic variation. The resulting dataset provides a resource to understand the molecular mechanisms of IB development in different common carp strains. These SNPs are potential markers for future selection to generate IB-reduced common carp.

Parallel subgenome structure and divergent expression evolution of allo-tetraploid common carp and goldfish.

How two subgenomes in allo-tetraploids adapt to coexistence and coordinate through structure and expression evolution requires extensive studies. In the present study, we report an improved genome assembly of allo-tetraploid common carp, an updated genome annotation of allo-tetraploid goldfish and the chromosome-scale assemblies of a progenitor-like diploid Puntius tetrazona and an outgroup diploid Paracanthobrama guichenoti. Parallel subgenome structure evolution in the allo-tetraploids was featured with equivalent chromosome components, higher protein identities, similar transposon divergence and contents, homoeologous exchanges, better synteny level, strong sequence compensation and symmetric purifying selection. Furthermore, we observed subgenome expression divergence processes in the allo-tetraploids, including inter-/intrasubgenome trans-splicing events, expression dominance, decreased expression levels, dosage compensation, stronger expression correlation, dynamic functionalization and balancing of differential expression. The potential disorders introduced by different progenitors in the allo-tetraploids were hypothesized to be alleviated by increasing structural homogeneity and performing versatile expression processes. Resequencing three common carp strains revealed two major ecotypes and uncovered candidate genes relevant to growth and survival rate.

Successively triggered Rod-shaped protocells for enhanced tumor Chemo-Photothermal therapy.

Abundant existence of extracellular matrix biological hydrogels in solid tumors precludes most therapeutics to arrive at intracellular target sites, which is probably one of the threatened reasons of pancreatic ductal adenocarcinoma (PDAC) for public health. In this study, we designed a rod-shaped protocell nanoparticle loading with doxorubicin hydrochloride (Dox) and indocyanine green (ICG), denoted as Dox/ICG-RsPNs, for enhanced chemo-photothermal PDAC treatment. The enhanced therapeutic efficacy was achieved by successively enhancing penetration across matrix hydrogels, endocytosis, increasing local temperature under laser irradiation and hyperthermia-triggered Dox release to nucleus. We found that RsPNs with rod shape could easily penetrate across matrix hydrogel, exerting excellent tumor accumulation. Then RsPNs was internalized effectively by BxPC-3 cells via a caveolin-mediated endocytosis pathway. In addition, ICG endowed the Dox/ICG-RsPNs with photothermal effect and the photothermal conversion efficiency was calculated for 16.2%. Under irradiation, a great number of Dox transported to the nucleus via hyperthermia-induced release. Furthermore, we found that the relative tumor volume of Dox/ICG-RsPNs was merely 1.37 under irradiation at the end of pharmacodynamic studies, which was significantly lower than that of other groups. These findings will provide a promise on the rational design of drug delivery system for effective chemo-photothermal combination therapy to treat PDAC.

A chromosome-level genome of the mud crab (Scylla paramamosain estampador) provides insights into the evolution of chemical and light perception in this crustacean.

Mud crabs, found throughout the Indo-Pacific region, are coastal species that are important fisheries resources in many tropical and subtropical Asian countries. Here, we present a chromosome-level genome assembly of a mud crab (Scylla paramamosain). The genome is 1.55 Gb (contig N50 191 kb) in length and encodes 17,821 proteins. The heterozygosity of the assembled genome was estimated to be 0.47%. Effective population size analysis suggested that an initial large population size of this species was maintained until 200 thousand years ago. The contraction of cuticle protein and opsin genes compared with Litopenaeus vannamei is assumed to be correlated with shell hardness and light perception ability, respectively. Furthermore, the analysis of three chemoreceptor gene families, the odorant receptor (OR), gustatory receptor (GR) and ionotropic receptor (IR) families, suggested that the mud crab has no OR genes and shows a contraction of GR genes and expansion of IR genes. The numbers of the three gene families were similar to those in three other decapods but different from those in two nondecapods and insects. In addition, IRs were more diversified in decapods than in nondecapod crustaceans, and most of the expanded IRs in the mud crab genome were clustered with the antennal IR clades. These findings suggested that IRs might exhibit more diverse functions in decapods than in nondecapods, which may compensate for the smaller number of GR genes. Decoding the S. paramamosain genome not only provides insight into the genetic changes underpinning ecological traits but also provides valuable information for improving the breeding and aquaculture of this species.

Chiral Mesoporous Silica Materials: A Review on Synthetic Strategies and Applications.

Because of its tunable textural properties and chirality feature, chiral mesoporous silica (CMS) gained significant consideration in many fields and has been developed rapidly in recent years. In this review, we provide an overview of synthesis strategies for fabricating CMS together with its main applications. The properties of CMS, including morphology and mesostructures and enantiomer excess (ee), can be altered according to the synthetic conditions during the synthesis process. Despite its primary stage, CMS has attracted extensive attention in many fields. In particular, CMS nanoparticles are widely used for enantioselective resolution and adsorption of chiral compounds with desirable separation capability. Also, CMS acts as a promising candidate for the effective delivery of chiral or achiral drugs to produce a chiral-responsive manner. Moreover, CMS also plays an important role in chromatographic separations and asymmetric catalysis. There has been an in-depth review of the synthetic methods and mechanisms of CMS. And this review aims to give a deep insight into the synthesis and application of CMS, especially in recent years, and highlights the significance that it may have in the future.

Evaluation of the Solid Dispersion System Engineered from Mesoporous Silica and Polymers for the Poorly Water Soluble Drug Indomethacin: In Vitro and In Vivo.

This work explored absorption efficacy via an in vivo imaging system and parallel artificial membrane penetration in indomethacin (IMC) solid dispersion (SD) systems. Two different polymer excipients-hydroxypropyl methylcellulose (HPMC) and Kollicoat IR as precipitation inhibitors (PIs)-combined with mesoporous silica nanoparticles (MSNs) as carriers were investigated. The IMC-SDs were prepared using the solvent evaporation method and characterized by solubility analysis, infrared (IR) spectroscopy, powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FESEM), and differential scanning calorimetry (DSC). It was confirmed that IMC successfully changed into an amorphous state after loading into the designed carriers. The in vitro release and stability experiments were conducted to examine the in vitro dissolution rates of IMC-SDs combined with HPMC and Kollicoat IR as PIs which both improved approximately three-fold to that of the pure drug. Finally, in vivo studies and in vitro parallel artificial membrane penetration (PAMPA) experiments ensured the greater ability of enhancing the dissolution rates of pure IMC in the gastrointestinal tract by oral delivery. In brief, this study highlights the prominent role of HPMC and Kollicoat IR as PIs in MSN SD systems in improving the bioavailability and gastrointestinal oral absorption efficiency of indomethacin.

Chiral mesoporous silica based LOFL delivery systems using achiral alcohols as co-structure-directing agents: Construction, characterization, sustained release and antibacterial activity.

The present work reported two synthesized chiral mesoporous silicas (CMSs) with opposite chirality for loading, release, and antibacterial activities of levofloxacin (LOFL). Herein, helical CMS nanorods were prepared by the sol-gel method using CTAB as a template and either n-heptanol or n-nonanol as a co-structure-directing agent (CSDA). The synthesized CMSs were characterised by transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), induced circular dichroism (ICD), and nitrogen adsorption/desorption. X-ray diffraction (XRD) was applied to confirm amorphous state transformation after drug loading, and thermal gravimetric analysis (TGA) was used to quantify the LOFL loading capacity. In vitro drug release studies from the loaded CMSs showed significant differences in the release behaviour for LOFL. Moreover, LOFL-loaded CMSs significantly sustained LOFL release with Fickian diffusion mechanism. Both the drug-loaded CMSs inhibited bacterial growth successfully when tested with strains of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Therefore, the prepared CMSs could find application as suitable vehicles for drug delivery systems to exert the therapeutic effects of LOFL and achieve different release behaviours.

Effect of Shape on Mesoporous Silica Nanoparticles for Oral Delivery of Indomethacin.

The use of mesoporous silica nanoparticles (MSNs) in the field of oral drug delivery has recently attracted greater attention. However, there is still limited knowledge about how the shape of MSNs affects drug delivery capacity. In our study, we fabricated mesoporous silica nanorods (MSNRs) to study the shape effects of MSNs on oral delivery. MSNRs were characterized by transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infrared spectroscopy (FTIR), and small-angle X-ray diffraction (small-angle XRD). Indomethacin (IMC), a non-steroidal anti-inflammatory agent, was loaded into MSNRs as model drug, and the drug-loaded MSNRs resulted in an excellent dissolution-enhancing effect. The cytotoxicity and in vivo pharmacokinetic studies indicated that MSNRs can be applied as a safe and efficient candidate for the delivery of insoluble drugs. The use of MSNs with a rod-like shape, as a drug delivery carrier, will extend the pharmaceutical applications of silica materials.