A Highly Tumor-Permeating DNA Nanoplatform for Efficient Remodeling of Immunosuppressive Tumor Microenvironments.

The immunosuppressive tumor microenvironment and limited intratumoral permeation have largely constrained the outcome of tumor therapy. Herein, we report a tailored DNA structure-based nanoplatform with striking tumor-penetrating capability for targeted remodeling of the immunosuppressive tumor microenvironment in vivo. In our design, chemo-immunomodulator (gemcitabine) can be precisely grafted on DNA sequences through a reactive oxygen species (ROS)-sensitive linker. After self-assembly, the gemcitabine-grafted DNA structure can site-specifically organize legumain-activatable melittin pro-peptide (promelittin) on each vertex for intratumoral delivery and further function as the template to load photosensitizers (methylene blue) for ROS production. The tailored DNA nanoplatform can achieve targeted accumulation, highly improved intratumoral permeation, and efficient immunogenic cell death of tumor cells by laser irradiation. Finally, the immunosuppressive tumor microenvironment can be successfully remodeled by reducing multi-type immunosuppressive cells and enhancing the infiltration of cytotoxic lymphocytes in the tumor. This rationally developed multifunctional DNA nanoplatform provides a new avenue for the development of tumor therapy.

Analyzing the tourism efficiency and its influencing factors of China's coastal provinces.

Tourism efficiency has become an important role in promoting tourism competitiveness and driving sustainable development. It is particularly important to identify and agnalyze the factors and mechanisms that affect efficiency. This paper firstly evaluates the tourism efficiency of 11 coastal provinces regions in China from 2010 to 2020 by using the DEA-BBC model that includes undesirable outputs. After that, it investigates the internal driving mechanism of the efficiency change through the Malmquist index and its decomposition. Finally, it analyzes the external influencing elements of tourist efficiency by the Tobit model. The results show that: (1) Although the average value of the tourism efficiency was changed from 0.727 to 0.707, it does not achieve the target. Its trend shows fluctuating from 2010-2020, which indicates that the tourism efficiency of most provincial regions is not optimal. The main factor that restricts tourism efficiency is scale efficiency. (2) By analyzing the dynamic trend, it is found that the average increase of technical efficiency is 14.0%, the average increase of technical change is 9.5%, and the average increase of MI index is 25.4%. It indicates that the overall tourism efficiency of 11 coastal provinces region in China is on the rise. (3) The spatial difference of tourism efficiency is significant, but there is no obvious spatial correlation. (4) The influencing factors of tourism efficiency are consumer demand, industrial structure, labor force and urbanization.

Investigating the potential causal association between consumption of green tea and risk of lung cancer: a study utilizing Mendelian randomization.

Background: Lung cancer is the most common global cancer in terms of incidence and mortality. Its main driver is tobacco smoking. The identification of modifiable risk factors isa public health priority. Green tea consumption has been examined in epidemiological studies, with inconsistent findings. Thus, we aimed to apply Mendelian randomization to clarify any causal link between green tea consumption and the risk of lung cancer. Methods: We utilized a two-sample Mendelian randomization (MR) approach. Genetic variants served as instrumental variables. The goal was to explore a causal link between green tea consumption and different lung cancer types. Green tea consumption data was sourced from the UK Biobank dataset, and the genetic association data for various types of lung cancer were sourced from multiple databases. Our analysis included primary inverse-variance weighted (IVW) analyses and various sensitivity test. Results: No significant associations were found between green tea intake and any lung cancer subtypes, including non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma) and small cell lung cancer. These findings were consistent when applying multiple Mendelian randomization methods. Conclusion: Green tea does not appear to offer protective benefits against lung cancer at a population level. However, lung cancer's complex etiology and green tea's potential health benefitssuggest more research is needed. Further studies should include diverse populations, improved exposure measurements and randomized controlled trials, are warranted.

Chemically Conjugated Branched Staples for Super-DNA Origami.

DNA origami, comprising a long folded DNA scaffold and hundreds of linear DNA staple strands, has been developed to construct various sophisticated structures, smart devices, and drug delivery systems. However, the size and diversity of DNA origami are usually constrained by the length of DNA scaffolds themselves. Herein, we report a new paradigm of scaling up DNA origami assembly by introducing a novel branched staple concept. Owing to their covalent characteristics, the chemically conjugated branched DNA staples we describe here can be directly added to a typical DNA origami assembly system to obtain super-DNA origami with a predefined number of origami tiles in one pot. Compared with the traditional two-step coassembly system (yields <10%), a much greater yield (>80%) was achieved using this one-pot strategy. The diverse superhybrid DNA origami with the combination of different origami tiles can be also efficiently obtained by the hybrid branched staples. Furthermore, the branched staples can be successfully employed as the effective molecular glues to stabilize micrometer-scale, super-DNA origami arrays (e.g., 10 × 10 array of square origami) in high yields, paving the way to bridge the nanoscale precision of DNA origami with the micrometer-scale device engineering. This rationally developed assembly strategy for super-DNA origami based on chemically conjugated branched staples presents a new avenue for the development of multifunctional DNA origami-based materials.

Compact gas cell for simultaneous detection of atmospheric aerosol optical properties based on photoacoustic spectroscopy and integrating sphere scattering enhancement.

Atmospheric aerosols play a pivotal role in the earth-atmospheric system. Analyzing their optical properties, specifically absorption and scattering coefficients, is essential for comprehending the impact of aerosols on climate. When different optical properties of aerosols are individually measured using multiple devices, cumulative errors in the detection results inevitably occur. To address this challenge, based on photoacoustic spectroscopy (PAS) and integrating sphere (IS) scattering enhancement, a compact gas cell (PASIS-Cell) was developed. The PASIS-Cell comprises a dual-T-type photoacoustic cell (DTPAC) and an IS. IS is coupled with DTPAC through a transparent quartz tube, thereby enhancing the scattering signal without compromising the acoustic characteristics of DTPAC. Concurrently, DTPAC can realize high-performance photoacoustic detection of absorption signal. Experimental results demonstrate that PASIS-Cell can simultaneously invert atmospheric aerosol absorption and scattering coefficients, with a minimum detection limit of less than 1 Mm-1, showcasing its potential in the analysis of aerosol optical properties.

A DNA Origami-Based Gene Editing System for Efficient Gene Therapy in Vivo.

DNA nanostructures have played an important role in the development of novel drug delivery systems. Herein, we report a DNA origami-based CRISPR/Cas9 gene editing system for efficient gene therapy in vivo. In our design, a PAM-rich region precisely organized on the surface of DNA origami can easily recruit and load sgRNA/Cas9 complex by PAM-guided assembly and pre-designed DNA/RNA hybridization. After loading the sgRNA/Cas9 complex, the DNA origami can be further rolled up by the locking strands with a disulfide bond. With the incorporation of DNA aptamer and influenza hemagglutinin (HA) peptide, the cargo-loaded DNA origami can realize the targeted delivery and effective endosomal escape. After reduction by GSH, the opened DNA origami can release the sgRNA/Cas9 complex by RNase H cleavage to achieve a pronounced gene editing of a tumor-associated gene for gene therapy in vivo. This rationally developed DNA origami-based gene editing system presents a new avenue for the development of gene therapy.

Genetically Encoded DNA Origami for Gene Therapy In Vivo.

DNA origami has played an important role in various biomedical applications, including biosensing, bioimaging, and drug delivery. However, the function of the long DNA scaffold involved in DNA origami has yet to be fully exploited. Herein, we report a general strategy for the construction of a genetically encoded DNA origami by employing two complementary DNA strands of a functional gene as the DNA scaffold for gene therapy. In our design, the complementary sense and antisense strands can be directly folded into two DNA origami monomers by their corresponding staple strands. After hybridization, the assembled genetically encoded DNA origami with precisely organized lipids on the surface can function as the template for lipid growth. The lipid-coated and genetically encoded DNA origami can efficiently penetrate the cell membrane for successful gene expression. After decoration with the tumor-targeting group, the antitumor gene (p53) encoded DNA origami can elicit a pronounced upregulation of the p53 protein in tumor cells to achieve efficient tumor therapy. The targeting group-modified, lipid-coated, and genetically encoded DNA origami has mimicked the functions of cell surface ligands, cell membrane, and nucleus for communication, protection, and gene expression, respectively. This rationally developed combination of folding and coating strategies for genetically encoded DNA origami presents a new avenue for the development of gene therapy.

Genetic Signature of Pinctada fucata Inferred from Population Genomics: Source Tracking of the Invasion in Mischief Reef of Nansha Islands.

Among the anthropogenic stresses that marine ecosystems face, biological invasions are one of the major threats. Recently, as a result of increasingly intense anthropogenic disturbance, numerous marine species have been introduced to their non-native ranges. However, many introduced species have uncertain original sources. This prevents the design and establishment of methods for controlling or preventing these introduced species. In the present study, genomic sequencing and population genetic analysis were performed to detect the geographic origin of the introduced Pinctada fucata population in the Mischief Reef of the South China Sea. The results of population genetic structure analysis showed a close relationship between the Mischief Reef introduced population and the Lingshui population, indicating that Lingshui may be the potential geographical origin. Furthermore, lower heterozygosity and nucleotide diversity were observed in the introduced population in Mischief Reef, indicating lower genetic diversity than in other native populations. We also identified some selected genomic regions and genes of the introduced population, including genes related to temperature and salinity tolerance. These genes may play important roles in the adaptation of the introduced population. Our study will improve our understanding of the invasion history of the P. fucata population. Furthermore, the results of the present study will also facilitate further control and prevention of invasion in Mischief Reef, South China Sea.

Stimuli-responsive nucleic acid nanostructures for efficient drug delivery.

Based on complementary base pairing, nucleic acid molecules have acted as engineerable building blocks to prepare versatile nanostructures with unique shapes and sizes. Benefiting from excellent programmability and biocompatibility, rationally designed nucleic acid nanostructures have been widely employed in biomedical applications. With the development of the chemical biology of nucleic acids, various stimuli-responsive nucleic acid nanostructures have been constructed by tailored chemical modification with multifunctional components. In this minireview, we summarize the representative and latest research about the employment of stimuli-responsive nucleic acid nanostructures for drug delivery in response to endogenous and exogenous stimuli (redox gradient, pH, nuclease, biomacromolecule, and light). We also discuss the broad prospects and remaining challenges of nucleic acid nanotechnology in biomedical applications.

The complete mitochondrial genome and phylogenetic analysis of the ocellated angelshark: Squatina tergocellatoides Chen, 1963.

The ocellated angelshark (Squatina tergocellatoides Chen, 1963) is a threatened shark within the family Squatinidae. In the present study, we reported the mitochondrial genome sequence of the ocellated angelshark. The complete mitochondrial genome is 16,683 bp in length and contains 37 mitochondrial genes and a control region as similar to most fishes. In addition, we constructed a maximum-likelihood phylogenetic tree of S. tergocellatoides and its relative species. This work will provide molecular data for further studies on S. tergocellatoides.

Modulating the Energy Band Structure of the Mg-Doped Sr0.5Pr0.5Fe0.2Mg0.2Ti0.6O3-δ Electrolyte with Boosted Ionic Conductivity and Electrochemical Performance for Solid Oxide Fuel Cells.

Achieving fast ionic conductivity in the electrolyte at low operating temperatures while maintaining the stable and high electrochemical performance of solid oxide fuel cells (SOFCs) is challenging. Herein, we propose a new type of electrolyte based on perovskite Sr0.5Pr0.5Fe0.4Ti0.6O3-δ for low-temperature SOFCs. The ionic conducting behavior of the electrolyte is modulated using Mg doping, and three different Sr0.5Pr0.5Fe0.4-xMgxTi0.6O3-δ (x = 0, 0.1, and 0.2) samples are prepared. The synthesized Sr0.5Pr0.5Fe0.2Mg0.2Ti0.6O3-δ (SPFMg0.2T) proved to be an optimal electrolyte material, exhibiting a high ionic conductivity of 0.133 S cm-1 along with an attractive fuel cell performance of 0.83 W cm-2 at 520 °C. We proved that a proper amount of Mg doping (20%) contributes to the creation of an adequate number of oxygen vacancies, which facilitates the fast transport of the oxide ions. Considering its rapid oxide ion transport, the prepared SPFMg0.2T presented heterostructure characteristics in the form of an insulating core and superionic conduction via surface layers. In addition, the effect of Mg doping is intensively investigated to tune the band structure for the transport of charged species. Meanwhile, the concept of energy band alignment is employed to interpret the working principle of the proposed electrolyte. Moreover, the density functional theory is utilized to determine the perovskite structures of SrTiO3-δ and Sr0.5Pr0.5Fe0.4-xMgxTi0.6O3-δ (x = 0, 0.1, and 0.2) and their electronic states. Further, the SPFMg0.2T with 20% Mg doping exhibited low dissociation energy, which ensures the fast and high ionic conduction in the electrolyte. Inclusively, Sr0.5Pr0.5Fe0.4Ti0.6O3-δ is a promising electrolyte for SOFCs, and its performance can be efficiently boosted via Mg doping to modulate the energy band structure.

Complete Mitochondrial Genome of Two Ectoparasitic Capsalids (Platyhelminthes: Monogenea: Monopisthocotylea): Gene Content, Composition, and Rearrangement.

The capsalid monogeneans are important pathogens that generally infect marine fishes and have a substantial impact on fish welfare in aquaculture systems worldwide. However, the current mitogenome information on capsalids has received little attention, limiting the understanding of their evolution and phylogenetic relationships with other monogeneans. This paper reports the complete mitochondrial genomes of Capsala katsuwoni and Capsala martinieri for the first time, which we obtained using a next-generation sequencing method. The mitogenomes of C. katsuwoni and C. martinieri are 13,265 and 13,984 bp in length, respectively. Both species contain the typical 12 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. The genome compositions show a moderate A+T bias (66.5% and 63.9% for C. katsuwoni and C. martinieri, respectively) and exhibit a negative AT skew but a positive GC skew in both species. One gene block rearrangement was found in C. katsuwoni in comparison with other capsalid species. Instead of being basal to the Gyrodactylidea and Dactylogyridea or being clustered with Dactylogyridea, all species of Capsalidea are grouped into a monophyletic clade. Our results clarify the gene rearrangement process and evolutionary status of Capsalidae and lay a foundation for further phylogenetic studies of monogeneans.

Transcriptomic analysis of male three-spot swimming crab (Portunus sanguinolentus) infected with the parasitic barnacle Diplothylacus sinensis.

Diplothylacus sinensis is reported as an intriguing parasitic barnacle that can negatively affect the growth, molting, reproduction in several commercially important portunid crabs. To better understand the molecular mechanisms of host-parasite interactions, we characterized the gene expression profiles from the healthy and D. sinensis infected Portunus sanguinolentus by high-through sequence method. Totally, the transcriptomic analysis generated 52, 266, 600 and 51, 629, 604 high quality reads from the infected and control groups, respectively. The clean reads were assembled to 90,740 and 69,314 unigenes, with the average length of 760 bp and 709 bp, respectively. The expression analysis showed that 18,959 genes were significantly changed by the parasitism of D. sinensis, including 4769 activated genes and 14,190 suppressed genes. The differentially expressed genes were categorized into 258 KEGG pathways and 647 GO terms. The GO analysis mapped 13 DEGs related to immune system process and 32 DEGs related to immune response, respectively, suggesting a potential alteration of transcriptional expression patterns in complement cascades of P. sanguinolentus. Additionally, 4 representative molting-related genes were down-regulated in parasitized group, indicating D. sinensis infection appeared to suppress the producing of ecdysteroid hormones. In conclusion, the present study improves our understanding on parasite-host interaction mechanisms, which focuses the function of Ecdysone receptor, Toll-like receptor and cytokine receptor of crustacean crabs infestation with rhizocephalan parasites.

Spatial Distribution, Potential Risks and Source Identification of Heavy Metals in the Coastal Sediments of the Northern Beibu Gulf, South China Sea.

Thirty samples of surface sediments (0-5 cm) from the northern Beibu Gulf were analyzed to determine the spatial distribution, potential risks and sources of six heavy metals (Cr, Cu, Zn, As, Cd and Pb). The concentrations (mg/kg, dw) of Cr, Cu, Zn, As, Cd and Pb were 15.38 ± 6.06, 6.54 ± 3.23, 41.86 ± 17.03, 6.92 ± 2.75, 0.04 ± 0.02 and 17.13 ± 6.38, respectively. Higher levels of Cr, Cu, Cd and Zn were observed in the western part of the study area. According to the potential ecological risk indexes and sediment quality guidelines, the measured metals were assessed at low contamination levels, with Pb posing the largest ecological risks. The results of positive matrix factorization (PMF) indicated that Cr and Zn mainly originated from natural geological background sources, while Cu, As, Cd and Pb were influenced by anthropogenic sources such as atmospheric deposition and anthropogenic activities. These three sources contributed 60.4%, 28.1% and 11.5% of the heavy metals, respectively. In addition, further research should be conducted focusing on the general relationships between As and various controls in sediments of the northern Beibu Gulf.

Efficient and Sustainable in†situ Photo-Fenton Reaction to Remove Phenolic Pollutants by NH2 -MIL-101(Fe)/Ti3 C2 Tx Schottky-Heterojunctions.

Metal-organic frameworks (MOFs) with abundant active sites, a class of materials composed of metal nodes and organic ligands, is widely used for photocatalytic degradation of pollutants. However, the rapid recombination of photoinduced carriers of MOFs limits its photocatalytic degradation performance. Herein, Ti3 C2 Tx nanosheets-based NH2 -MIL-101(Fe) hybrids with Schottky-heterojunctions were fabricated by in situ hydrothermal assembly for improved photocatalytic activity. The photodegradation efficiencies of the NH2 -MIL-101(Fe)/Ti3 C2 Tx (N-M/T) hybrids for phenol and chlorophenol were 96.36 % and 99.83 % within 60 minutes, respectively. The N-M/T Schottky-heterojunction duly transferred electrons to the Ti3 C2 Tx nanosheets surface via built-in electric fields, effectively suppressing the recombination of photogenerated carriers, thereby improving the photocatalytic performance of NH2 -MIL-101(Fe). Moreover, the Fe-mixed-valence in the N-M/T led to improvement in the efficiency of the in situ generated photo-Fenton reactions, further enhancing the photocatalytic activity with more generated reactive oxygen species (ROS). The study proposes a highly effective removal of phenolic pollutants in wastewater.

Chemically modified DNA nanostructures for drug delivery.

Based on predictable, complementary base pairing, DNA can be artificially pre-designed into versatile DNA nanostructures of well-defined shapes and sizes. With excellent addressability and biocompatibility, DNA nanostructures have been widely employed in biomedical research, such as bio-sensing, bio-imaging, and drug delivery. With the development of the chemical biology of nucleic acid, chemically modified nucleic acids are also gradually developed to construct multifunctional DNA nanostructures. In this review, we summarize the recent progress in the construction and functionalization of chemically modified DNA nanostructures. Their applications in the delivery of chemotherapeutic drugs and nucleic acid drugs are highlighted. Furthermore, the remaining challenges and future prospects in drug delivery by chemically modified DNA nanostructures are discussed.

Impact of Material and Lens Design on Repositioning Surgery of Toric Intraocular Lenses: A Single-Arm Meta-Analysis.

AIM: To analyze the pooled incidence rate in repositioning surgery by considering different materials and designs. METHODS: All published studies investigating the repositioning surgery of toric intraocular lenses (IOLs) before September 1, 2020, were searched and evaluated. The R3.5.2 software was used to extract the data, and a single arm meta-analysis was performed. RESULTS: 19 cases from 18 published studies articles were included in the meta-analysis. The pooled incidence rate in repositioning surgery was 2% (I 2 = 53%, P heterogeneity<0.01). Plate and silicone IOLs had significantly higher incidence rates (6% for each) than loop (2%) and hydrophobic acrylate (2%). Incidence rates of Acrysof, Staar, TECNIS, PhysIOL SA, T-flex 623T, and Microsil 6116TU groups were 1% (95% CI [1%-2%]), 6% (95% CI [4%-9%]), 3% (95% CI [2%-4%]), 1.40% (1/71), 3.03% (1/33), and 4.76% (1/21), respectively. CONCLUSIONS: The pooled incidence rate of repositioning surgery in IOLs was 2%. Materials and designs would be risk factors for the rotational stability of the toric IOLs. Pooled incidence rates of the hydrophobic acrylate and loop group were lower than those of the silicone and plate group. Product identity is the main driver of heterogeneity.

Next generation sequencing yields the complete mitochondrial genome of the darkfin hind Cephalopholis urodeta (Serranidae) from the Mischief Reef, South China Sea.

The complete mitochondrial genome of the Cephalopholis urodeta (Serranidae: Epinephelinae) was sequenced by next-generation sequencing method on the basis of one female specimen collected from coral reef areas at the Mischief Reef, South China Sea. The mitogenome is 16,593 bp in length, including 13 protein-coding genes, 22 tRNA genes, two rRNA genes and a D-loop region. The overall content of A + T is 55.66%, which is significantly higher than the C + G content (44.34%). Among four bases, C shows the lowest frequency (15.99%). Phylogenetic tree based on the 13 protein-coding genes was constructed for analyzing the position of C. urodeta. The results provide useful insights into further studies on population genetics and phylogenetics of groupers.

Electrochemiluminescence Resonance Energy Transfer System Based on Silver Metal-Organic Frameworks as a Double-Amplified Emitter for Sensitive Detection of miRNA-107.

As a class of electrochemiluminescence (ECL) enhancers, silver-based materials have broad application prospects. In this work, a novel silver metal-organic framework (AgMOF) was developed as a self-enhanced ECL emitter by one-step mixing and standing at room temperature. The AgMOF could produce strong and stable ECL emissions based on a double-amplification method, which originated from the aggregation-induced ECL emission of ligands and catalyzing S2O82- to produce more SO4•- by silver. Moreover, an ECL resonance energy transfer (ECL-RET) biosensor with AgMOF as a donor and BHQ2 as an acceptor was fabricated by duplex-specific nuclease (DSN)-assisted target recycling amplification to detect miRNA-107. The biosensor exhibited a strong ECL-RET effect due to the higher ECL emission of the AgMOF and perfect match of spectra between the AgMOF and BHQ2. Upon the introduction of DSN and target miRNAs, the specific DNA-RNA binding and nuclease cleaving could trigger the detachment of BHQ2, resulting in an increased ECL signal of AgMOF. Benefiting from the ECL-RET and DSN-assisted target recycling amplification methods, this biosensor achieved a wide linear relationship range from 20 to 120 fM with a low limit of detection (4.33 fM). This research presents an effective emitter for self-enhanced ECL systems, which broadens the potential ECL applications of silver-based nanomaterials.

The complete mitochondrial genome and phylogenetic analysis of the reticulated swellshark: Cephaloscyllium fasciatum Chan, 1966.

In the present study, the complete mitogenome of Cephaloscyllium fasciatum has been sequenced and assembled. The complete mitochondrial genome is 16,509 bp in length and contains 37 mitochondrial genes and a control region as other fishes. The nucleotide composition of C. fasciatum mitogenome showed an anti-G bias and an excess of AT content. Furthermore, maximum-likelihood phylogenetic tree was constructed based on 13 protein-coding genes of C. fasciatum and other 15 sharks. This work will provide molecular data for studies on phylogeny and evolution in the family Scyliorhinidae.