Chromosome-level genome assembly and annotation of the Yunling cattle with PacBio and Hi-C sequencing data.

Yunling cattle is a new breed of beef cattle bred in Yunnan Province, China. It is bred by crossing the Brahman, the Murray Grey and the Yunnan Yellow cattle. Yunling cattle can adapt to the tropical and subtropical climate environment, and has good reproductive ability and growth speed under high temperature and high humidity conditions, it also has strong resistance to internal and external parasites and with good beef performance. In this study, we generated a high-quality chromosome-level genome assembly of a male Yunling cattle using a combination of short reads sequencing, PacBio HiFi sequencing and Hi-C scaffolding technologies. The genome assembly(3.09 Gb) is anchored to 31 chromosomes(29 autosomes plus one X and Y), with a contig N50 of 35.97 Mb and a scaffold N50 of 112.01 Mb. It contains 1.62 Gb of repetitive sequences and 20,660 protein-coding genes. This first construction of the Yunling cattle genome provides a valuable genetic resource that will facilitate further study of the genetic diversity of bovine species and accelerate Yunling cattle breeding efforts.

Population Structure and Genetic Diversity of Yunling Cattle Determined by Whole-Genome Resequencing.

The Yunling cattle breed, a three-breed crossbreed, which comprises 50% Brahman cattle, 25% Murray Grey cattle and 25% Yunnan Yellow cattle, has several advantageous traits, including rapid growth, superior meat quality, ability to improve tolerance in hot and humid climates, tick resistance and rough feed. It can be rightfully stated that Yunling cattle serve as vital genetic repositories of the local Yunnan cattle. Gaining insights into the genetic information of Yunling cattle plays a significant role in the formulation of sound breeding strategies for this breed, safeguarding genetic resources and mitigating the risks associated with inbreeding depression. In this study, we constructed the Yunling cattle standard reference genome and aligned the whole genomes of 129 Yunling cattle individuals to the constructed reference genome to estimate the current genetic status of Yunling cattle in Yunnan Province, China. The average alignment rate and the average percentage of properly paired are both 99.72%. The average nucleotide diversity in Yunling cattle is 0.000166, which indicates a lower level of diversity. Population structure analysis classified Yunling cattle into two subgroups. Inbreeding analysis revealed that inbreeding events did occur in the Yunling cattle, which may have contributed to the low genetic diversity observed. This study presents a comprehensive assessment of the genetic structure and diversity among the Yunling cattle and provides a theoretical foundation for the preservation and exploitation of these precious germplasm resources.

Advances in colorimetric aptasensors for heavy metal ion detection utilizing nanomaterials: a comprehensive review.

Heavy metal ion contamination poses significant environmental and health risks, necessitating rapid and efficient detection methods. In the last decade, colorimetric aptasensors have emerged as powerful tools for heavy metal ion detection, owing to their notable attributes such as high specificity, facile synthesis, adaptability to modifications, long-term stability, and heightened sensitivity. This comprehensive overview summarizes the key developments in this field over the past ten years. It discusses the principles, design strategies, and innovative techniques employed in colorimetric aptasensors using nanomaterials. Recent advancements in enhancing sensitivity, selectivity, and on-site applicability are highlighted. The review also presents application studies of successful heavy metal ion detection using colorimetric aptasensors, underlining their potential for environmental monitoring and health protection. Finally, future directions and challenges in the continued evolution of these aptasensors are outlined.

Blocked Autophagy is Involved in Layered Double Hydroxide-Induced Repolarization and Immune Activation in Tumor-Associated Macrophages.

Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment (TME). The polar plasticity of TAMs makes them important targets for improving the immunosuppressive microenvironment of tumors. The previous study reveals that layered double hydroxides (LDHs) can effectively promote the polarization of TAMs from the anti-inflammatory M2 type to the pro-inflammatory M1 type. However, their mechanisms of action remain unexplored. This study reveals that LDHs composed of different cations exhibit distinct abilities to regulate the polarity of TAMs. Compared to Mg-Fe LDH, Mg-Al LDH has a stronger ability to promote the repolarization of TAMs from M2 to M1 and inhibit the formation of myeloid-derived suppressor cells (MDSCs). In addition, Mg-Al LDH restrains the growth of tumors in vivo and promotes the infiltration of activated immune cells into the TME more effectively. Interestingly, Mg-Al LDH influences the autophagy of TAMs; this negatively correlates with the pro-inflammatory ability of TAMs. Therefore, LDHs exert their polarization ability by inhibiting the autophagy of TAMs, and this mechanism might be related to the ionic composition of LDHs. This study lays the foundation for optimizing the performance of LDH-based immune adjuvants, which display excellent application prospects for tumor immunotherapy.

Layered Double Hydroxide-Loaded miR-30a for the Treatment of Breast Cancer In Vitro and In Vivo.

MicroRNAs (miRNAs) play an essential role in cancer therapy, but the disadvantages of its poor inherent stability, rapid clearance, and low delivery efficiency affect the therapeutic efficiency. Loading miRNAs by nanoformulations can improve their bioavailability and enhance therapeutic efficiency, which is an effective miRNA delivery strategy. In this study, we synthesized layered double hydroxides (LDH), which are widely used as carriers of drugs or genes due to the characteristics of good biocompatibility, high loading capacity, and pH sensitivity. We loaded the suppressor oncogene miR-30a on LDH nanomaterials (LDH@miR-30a) and determined the mass ratio of miRNA binding to LDH by agarose gel electrophoresis. LDH@miR-30a was able to escape the lysosomal pathway and was successfully phagocytosed by breast cancer SKBR3 cells and remained detectable in the cells after 24 h of co-incubation. In vitro experiments showed that LDH@miR-30a-treated SKBR3 cells showed decreased proliferation and cell cycle arrest in the G0/G1 phase and LDH@miR-30a was able to regulate the epithelial-mesenchymal transition (EMT) process and inhibit cell migration and invasion by targeting SNAI1. Meanwhile, in vivo experiments showed that nude mice treated with LDH@miR-30a showed a significant reduction in their solid tumors and no significant impairment of vital organs was observed. In conclusion, LDH@miR-30a is an effective drug delivery system for the treatment of breast cancer.

Interference of layered double hydroxide nanoparticles with pathways for biomedical applications.

Recent decades have witnessed a surge of explorations into the application of multifarious materials, especially biomedical applications. Among them, layered double hydroxides (LDHs) have been widely developed as typical inorganic layer materials to achieve remarkable advancements. Multiple physicochemical properties endow LDHs with excellent merits in biomedical applications. Moreover, LDH nanoplatforms could serve as "molecular switches", which are capable of the controlled release of payloads under specific physiological pH conditions but are stable during circulation in the bloodstream. In addition, LDHs themselves are composed of several specific cations and possess favorable biological effects or regulatory roles in various cellular functions. These advantages have caused LDHs to become increasingly of interest in the area of nanomedicine. Recent efforts have been devoted to revealing the potential factors that interfere with the biological pathways of LDH-based nanoparticles, such as their applications in shaping the functions of immune cells and in determining the fate of stem cells and tumor treatments, which are comprehensively described herein. In addition, several intracellular signaling pathways interfering with by LDHs in the above applications were also systematically expatiated. Finally, the future development and challenges of LDH-based nanomedicine are discussed in the context of the ultimate goal of practical clinical application.

A rapid quality grade discrimination method for Gastrodia elata powderusing ATR-FTIR and chemometrics.

Gastrodia elata is an obligate fungal symbiont used in traditional Chinese medicine. There are currently 4 grades of the plant based on the "Commodity Specification Standard of 76 Kinds of Medicinal Materials". The traditional discrimination methods for determining the medicinal grade of G. elata powders are complex and time-consuming which are not suitable for rapid analysis. We developed a rapid analysis method for this plant using attenuated total reflection and Fourier-transform infrared spectroscopy (ATR-FTIR) together with machine learning algorithms. The original spectroscopic data was first pre-treated using the multiplicative scatter correction (MSC) method and 4 principal components were extracted using extremely randomized trees (Extra-trees) and principal component analysis (PCA) algorithms, and different kinds of classification models were established. We found that multilayer perceptron classifier (MLPC) modeling was superior to support vector machine (SVM) and resulted in validation and prediction accuracies of 99.17% and 100%, respectively and a modeling time of 2.48 s. The methods established from the current study can rapidly and effectively distinguish the 4 different types of G. elata powders and thus provides a platform for rapid quality inspection.

Multifunctional silica nanocomposites prime tumoricidal immunity for efficient cancer immunotherapy.

The tumor immune microenvironment (TIME) has been demonstrated to be the main cause of cancer immunotherapy failure in various malignant tumors, due to poor immunogenicity and existence of immunosuppressive factors. Thus, establishing effective treatments for hostile TIME remodeling has considerable potential to enhance immune response rates for durable tumor growth retardation. This study aims to develop a novel nanocomposite, polyethyleneimine-modified dendritic mesoporous silica nanoparticles loaded with microRNA-125a (DMSN-PEI@125a) to synergistically enhance immune response and immunosuppression reversion, ultimately generating a tumoricidal environment. Our results showed that DMSN-PEI@125a exhibited excellent ability in cellular uptake by murine macrophages and the cervical cancer cell line TC-1, repolarization of tumor associated macrophages (TAMs) to M1 type in a synergistic manner, and promotion of TC-1 immunogenic death. Intratumor injection of DMSN-PEI@125a facilitated the release of more damage-related molecular patterns and enhanced the infiltration of natural killer and CD8+ T cells. Meanwhile, repolarized TAMs could function as a helper to promote antitumor immunity, thus inhibiting tumor growth in TC-1 mouse models in a collaborative manner. Collectively, this work highlights the multifunctional roles of DMSN-PEI@125a in generating an inflammatory TIME and provoking antitumor immunity, which may serve as a potential agent for cancer immunotherapy.

Layered double hydroxide eliminate embryotoxicity of chemotherapeutic drug through BMP-SMAD signaling pathway.

Recent studies indicate that exogenous chemotherapy agents can cross the placenta barrier and cause fetal toxicity, while there exists barely alternative therapy for pregnant cancer patients. Here, we show a robust protective effect of layered double hydroxide (LDH) against etoposide (VP16) induced in vitro mouse embryonic stem cells (mESCs) toxicity and in vivo embryo developmental disorders. The nano-composite system (L-V) abrogated the original VP16 generated mitochondrial mediated mESCs toxicity totally, surprisingly maintained the pluripotency without leukemia inhibitory factor (LIF) and prevented the down-regulation of ectoderm marker expression during spontaneous embryoid bodies differentiation. Fetal growth retardation, the related placenta and skeletal structural abnormalities and long-term toxicity in the offspring were generated when pregnant mice exposed to VP16, while these detrimental effects were abolished when substituted with L-V. The different uterine drug accumulation of VP16 and L-V contributed to partly cause for the functional variation. And further transcriptome analysis confirmed developmental related BMP4-SMAD6 signaling pathway is of crucial importance. Our study revealed the devastating effects of VP16 on embryonic development and the toxicity-relieve method using nano-carrier system, which will provide important guidance for clinical application of LDH as alternative therapeutic system with minimal side effects for pregnant women diagnosed with cancer.

Synergetic Functional Nanocomposites Enhance Immunotherapy in Solid Tumors by Remodeling the Immunoenvironment.

Checkpoint blockade immunotherapy has demonstrated significant clinical success in various malignant tumors. However, the therapeutic response is limited due to the immunosuppressive tumor microenvironment (ITM). In this study, a functional nanomaterial, layered double hydroxides (LDHs), carrying specific functional miR155 is developed to modulate ITM by synergistically repolarizing tumor associated macrophages (TAMs) to M1 subtype. LDH nanoparticles loaded with miR155 (LDH@155) exhibit superior ability in cellular uptake by murine macrophages, miR escape into the cytoplasm and TAMs specific delivery when introtumoral administration. Meanwhile, upon exposure to LDH@155, TAMs are significantly skewed to M1 subtype, which markedly inhibits myeloid-derived suppressor cells (MDSCs) formation and stimulates T-lymphocytes to secrete more interferon-γ (IFN-γ) cytokines in vitro. Introtumoral administration of LDH@155 reduces the percentage of TAMs and MDSCs in the tumor and elevates CD4+ and CD8+ T cell infiltration and activation, which can promote therapeutic efficiency of α-PD-1 antibody immunotherapy. Furthermore, it is found that LDH@155 significantly decreases the expression level of phosphorylated STAT3 and ERK1/2 and activates NF-κB expression in TAMs, indicating that the STAT3, ERK1/2, and NF-κB signaling pathways may involve in LDH@155-induced macrophage polarization. Overall, the results suggest that LDH@155 nanoparticles may, in the future, function as a promising agent for cancer combinational immunotherapy.

Facile synthesis by a covalent binding reaction for pH-responsive drug release of carboxylated chitosan coated hollow mesoporous silica nanoparticles.

In this study, a promising drug nano-carrier system consisting of mono-dispersed and pH sensitive carboxylated chitosan-hollow mesoporous silica nanoparticles (Ccs-HMSNs) suitable for the treatment of malignant cells was synthesised and investigated. At neutral pH, the Ccs molecules are orderly aggregated state, which could effectively hinder the release of loaded drug molecules. However, in slightly acidic environment, Ccs chains are heavily and flexibly entangled in gel state, which would enhance the subsequent controlled release of the loaded drug. Using doxorubicin hydrochloride (DOX•HCl) as the drug model, their results demonstrated that the system had an excellent loading efficiency (64.74 µg/mg Ccs-HMSNs) and exhibited a pH-sensitive release behaviour. Furthermore, confocal laser scanning microscopy revealed that the Ccs-HMSNs nanocomposite could effectively deliver and release DOX•HCl to the nucleus of HeLa cells, thereby inducing apoptosis. In addition, MTT assay also confirmed that DOX•HCl loaded Ccs-HMSNs (DOX•HCl@Ccs-HMSNs) exhibited a good anticancer effect on HeLa cells with a time-dependent manner. Finally, haemolysis experiment showed Ccs-HMSNs had no haemolytic activity at all the tested concentrations (5-320 µg/mL). Thus, this biocompatible and effective nano-carrier system will have potential applications in controllable drug delivery and cancer therapy.

Curcumin-Loaded TPGS/F127/P123 Mixed Polymeric Micelles for Cervical Cancer Therapy: Formulation, Characterization, and InVitro and InVivo Evaluation.

Cervical cancer is the fourth most common cancer in women worldwide, and existing treatments cause severe side effects and great burdens. Thus, the development of safe, inexpensive therapeutic agents is necessary. Curcumin (Cur), a well-known natural product, exerts promising anti-cancer activities against various cancer types. However, its therapeutic efficacy is severely restrained due to rapid degradation, poor aqueous solubility, and low bioavailability. The objective of this study was to investigate the therapeutic potential of novel curcumin-loaded TPGS/F127/P123 mixed polymeric micelles (Cur@NPT100) for cervical cancer treatment. The Cur@NPT100 exhibited an average size of approximately 19 nm, a zeta potential of around -4 mV, a drug loading of 8.18 ± 0.36%, and an encapsulation efficiency of 79.38 ± 4.65%. Unlike free Cur, Cur@NPT100 are readily dispersed in aqueous medium, showing enhanced stability and a sustained release profile over a 6-day period. In vitro cell culture experiments revealed that TPGS/F127/P123 mixed polymeric micelles (NPT100) based nanocarriers substantially promoted the selective cellular uptake of Cur into HeLa cells rather than by non-cancerous NIH3T3 cells, inducing higher cytotoxicity and greater apoptosis and significantly increasing the percentage of cells arrested at the G2/M phase of the cell cycle. Additionally, the Cur@NPT100 facilitated more Cur accumulation in the mitochondria and decreased the mitochondrial membrane potential. In addition, western blot assays demonstrated that Cur@NPT100 were more potent than free Cur at activating the mitochondria-mediated apoptosis pathway. In vivo results further confirmed that Cur@NPT100 exhibited a much higher antitumor efficacy than free Cur and had excellent biocompatibility. In conclusion, Cur@NPT100 might be an effective therapeutic agent for cervical cancer.

Rational Design of Multifunctional Dendritic Mesoporous Silica Nanoparticles to Load Curcumin and Enhance Efficacy for Breast Cancer Therapy.

Breast cancer is the primary reason for cancer-related death in women worldwide and the development of new formulations to treat breast cancer patients is crucial. Curcumin (Cur), a natural product, exerts promising anticancer activities against various cancer types. However, its therapeutic efficacy is hindered as a result of poor water solubility, instability, and low bioavailability. The aim of this work is to assess the curative effect of a novel nanoformulation, i.e., Cur-loaded and calcium-doped dendritic mesoporous silica nanoparticles modified with folic acid (Cur-Ca@DMSNs-FA) for breast cancer therapy. The results manifested that Cur-Ca@DMSNs-FA dispersed very well in aqueous solution, released Cur with a pH-responsible profile, and targeted efficiently to human breast cancer MCF-7 cells. Further investigations indicated that Cur-Ca@DMSNs-FA effectively inhibited cell proliferation, increased intracellular ROS generation, decreased mitochondrial membrane potential, and enhanced cell cycle retardation at G2/M phase, leading to a higher apoptosis rate in MCF-7 compared to free Cur. Moreover, the Western blotting analysis demonstrated that Cur-Ca@DMSNs-FA were more active than free Cur through suppression of PI3K/AKT/mTOR and Wnt/ß-catenin signaling, and activation of the mitochondria-mediated apoptosis pathway. In addition, hemolysis assay showed that the Ca@DMSNs-FA exhibited good biocompatibility. Last, in vivo studies indicated that when Cur was encapsulated in Ca@DMSNs-FA, the Cur concentration in blood serum and tumor tissues was increased after 1 h intraperitoneal injection. In conclusion, Cur-Ca@DMSNs-FA might act as a potential anticancer drug formulation for breast cancer therapy.

Molecular characterization of an Apolipophorin-III gene from the Chinese oak silkworm, Antheraea pernyi (Lepidoptera: Saturniidae).

Apolipophorin-III (ApoLp-III) acts in lipid transport, lipoprotein metabolism, and innate immunity in insects. In this study, an ApoLp-III gene of Antheraea pernyi pupae (Ap-ApoLp-III) was isolated and characterized. The full-length cDNA of Ap-ApoLp-III is 687 bp, including a 5'-untranslated region (UTR) of 40 bp, 3'-UTR of 86 bp and an open reading frame of 561 bp encoding a polypeptide of 186 amino acids that contains an Apolipophorin-III precursor domain (PF07464). The deduced Ap-apoLp-III protein sequence has 68, 59, and 23% identity with its orthologs of Manduca sexta, Bombyx mori, and Aedes aegypti, respectively. Phylogenetic analysis showed that the Ap-apoLp-III was close to that of Bombycoidea. qPCR analysis revealed that Ap-ApoLp-III expressed during the four developmental stages and in integument, fat body, and ovaries. After six types of microorganism infections, expression levels of the Ap-ApoLp-III gene were upregulated significantly at different time points compared with control. RNA interference (RNAi) of Ap-ApoLp-III showed that the expression of Ap-ApoLp-III was significantly downregulated using qPCR after injection of E. coli. We infer that the Ap-ApoLp-III gene acts in the innate immunity of A. pernyi.