Bortezomib-encapsulated metal-phenolic nanoparticles for intracellular drug delivery.

Bortezomib (BTZ) is an important boronate proteasome inhibitor that is widely used in cancer therapy. However, the clinical application of BTZ suffers from poor stability and serious adverse effects. Herein, we fabricated metal-polyphenol nanoparticles for the covalent encapsulation of BTZ. BTZ-encapsulated tannic acid (TA)-Fe3+ nanoparticles can be prepared by mixing BTZ, TA, and ferric chloride owing to the formation of metal-polyphenol coordination interaction and dynamic boronate ester bonds. The BTZ-encapsulated TA-Fe3+ nanoparticles (BTZ NPs) are stable in physiological environment (pH 7.4) with minimal drug leakage. However, BTZ NPs can be disassembled in an acidic environment. Therefore, BTZ can be rapidly released from BTZ NPs in an acidic environment (pH 5.0). More than 50% BTZ can be released from BTZ NPs after 8 h incubation at pH 5.0. BTZ NPs exhibited high cytotoxicity against human osteosarcoma Saos-2 cells and human multiple myeloma OPM-2 cells. The metal-polyphenol nanoparticles can be a promising nanoplatform for the delivery of BTZ with simultaneously enhanced therapeutic efficacy and reduced side effects.

Fast Low-Sidelobe Pattern Synthesis Using the Symmetry of Array Geometry.

Array pattern synthesis with low sidelobe levels is widely used in practice. An effective way to incorporate sensor patterns in the design procedure is to use numerical optimization methods. However, the dimension of the optimization variables is very high for large-scale arrays, leading to high computational complexity. Fortunately, sensor arrays used in practice usually have symmetric structures that can be utilized to accelerate the optimization algorithms. This paper studies a fast pattern synthesis method by using the symmetry of array geometry. In this method, the problem of amplitude weighting is formulated as a second-order cone programming (SOCP) problem, in which the dynamic range of the weighting coefficients can also be taken into account. Then, by utilizing the symmetric property of array geometry, the dimension of the optimization problem as well as the number of constraints can be reduced significantly. As a consequence, the computational efficiency is greatly improved. Numerical experiments show that, for a uniform rectangular array (URA) with 1024 sensors, the computational efficiency is improved by a factor of 158, while for a uniform hexagonal array (UHA) with 1261 sensors, the improvement factor is 284.

Modification of polyvinylidene fluoride membrane with ciprofloxacin to improve the bacteriostatic performance.

The common polyvinylidene fluoride (PVDF) membrane itself is susceptible to membrane fouling, especially biofouling, which is a serious threat. In this study, PVDF membrane was modified with ciprofloxacin (CIP) through co-blending to investigate the filtration properties, bacterial inhibition and fouling resistance. Modified membranes were prepared by adding 0.3 g (MC0.3), 0.6 g (MC0.6), 0.9 g (MC0.9) and 1.2 g (MC1.2) CIP per 100 g casting solution. Among these modified membranes, MC0.6 showed the best filtration performances, with the pure water flux stabilized at about 416.67 L/(m2·h) and bovine serum albumin (BSA) rejection of 92.0% at a trans-membrane pressure of 0.1 MPa. The pore size was reduced, the average roughness was reduced to 29.4 nm, the contact angle was lowered to 68.9°, and the hydrophilicity was greatly improved. The width of the inhibition circle produced by MC0.6 was 0.35-0.45 mm, and the modified membrane showed good inhibition of non-specific bacteria and algal removal during urban river water filtration. The rejection of BSA was increased by 16.32% compared to the base membrane and the adsorption rate for BSA was reduced by 68.45%. In addition, the removal of conventional pollutants in urban river water by the modified membranes for was also improved. Compared with that of the base membrane, the removal of TN, NH3-N, TP and COD by MC0.6 was increased by 10.58%, 12.45%, 15.44% and 13.53%. The results showed that CIP co-blending modified PVDF membrane could effectively improve membrane performances and has good value for water treatment.

Screening of Reference Genes for Quantitative Real-Time PCR Analysis in Tissues and during Testis Development, and Application to Analyze the Expression of kifc1 in Hemibarbus labeo (Teleostei, Cypriniformes, Cyprinidae).

The selection of proper reference genes is vital for ensuring precise quantitative real-time PCR (qPCR) assays. This study evaluates the stability of the expression of nine candidate reference genes in different tissues and during testicular development in H. labeo. The results show that eef1a is recommended as a reference gene for qPCR analysis in tissues and during testicular development. Furthermore, we evaluated the optimal number of reference genes needed when calculating gene expression levels using the geomean method, revealing that two reference genes are sufficient. Specifically, eef1a and rps27 are recommended for analysis of gene expression in tissues, whereas eef1a and actb are advised for evaluating gene expression during testicular development. In addition, we examined the expression pattern of kifc1, a kinesin involved in the reshaping of spermatids. We detected peak expression levels of kifc1 in testes, with its expression initially increasing before decreasing throughout testicular development. The highest expression of kifc1 was observed in stage IV testes, the active period of spermiogenesis, suggesting a possible role for kifc1 in the regulation of the reshaping of spermatids and hence testicular development. This study represents the first investigation of reference genes for H. labeo, providing a foundation for studying gene expression patterns and investigating gene expression regulation during testicular development.

Functional insights of digestion, absorption, and immunity in different segments of the intestine in Hemibarbus labeo from transcriptomic analysis.

The intestine is an important organ for food digestion and absorption and body immunity in fish. In this study, we investigated the abundance of transcripts from different segments of the intestinal tract using transcriptome sequencing technology in Hemibarbus labeo, to provide functional insights into digestion, absorption, and immunity in the anterior intestine (AI), middle intestine (MI), and posterior intestine (PI). We found 5646 differentially expressed genes (DEGs), which were significantly enriched to GO terms of carbohydrate metabolic process, transmembrane transport, iron ion binding, lipid metabolic process, and KEGG pathway of fat digestion and absorption, mineral absorption, protein digestion and absorption, vitamin digestion and absorption, indicating that the digestion and absorption function of food is different in AI, MI, and PI. In practice, most genes, enriched in the KEGG pathway for digestion and absorption of nutrients, are upregulated in AI and MI, indicating stronger roles for food digestion and absorption in these segments. Furthermore, we found that genes involved in the KEGG pathway of lysosome and endocytosis pathway are upregulated in PI, suggesting stronger antigen-presenting capabilities in PI. However, some cytokine receptor genes, including ccr4, cxcr2, tnfrsf9, il6r, csf3r, and cxcr4, are highly expressed in AI, reflecting the regional immune specialization in different segments. This study provides functional insights into digestion, absorption, and immunity in different segments of the intestine and supports the regional functional specialization within different segments of the intestine in H. labeo.

Histological and Transcriptomic Insights into the Ovary Development of Hemibarbus labeo Injected with Spawn-Inducing Hormones.

Naturally, the ovaries of many farmed fish can only develop to stage IV (mainly including stage IV oocytes, known as full-grown postvitellogenic oocytes). Therefore, spawn-inducing hormone injections are used to promote ovary development and oocyte maturation, facilitating reproduction in the aquaculture industry. The study of spawn-inducing hormones and their underlying neuroendocrine mechanisms has been a recent focus in fish reproductive biology. However, the intra-ovarian regulatory mechanisms of ovary development and oocyte maturation after hormone injection require further investigation. In this study, we explored the histological and transcriptomic map of the ovary of Hemibarbus labeo after hormone injection to reveal changes in the ovary. The gonad index significantly increased after hormone injection for 5.5 h, after which no significant change was observed. Histological analysis showed that the nuclei had moved to one side of the oocytes at 5.5 h after hormone injection. Moreover, the volume of the oocytes increased and their yolk membranes thickened. Oocytes then underwent their first meiotic division at 5.5-11 h after hormone injection. Subsequently, the follicular membrane was ruptured, and ovulation was completed at 11-16.5 h after hormone injection. In addition, we identified 3189 differentially expressed genes (DEGs) on comparing the transcriptomes at different time points after hormone injection. These DEGs were significantly enriched in the GO terms of nervous system process, molecular transducer activity, and extracellular region, and the KEGG pathways of TNF signaling and cytokine-cytokine receptor interaction; these may play important roles in ovary development and oocyte maturation. Within these pathways, genes such as apoe, creb3, jun, junb, il11, and il8 may play important roles in steroid hormone synthesis and ovulation. Conclusively, our results show detailed sequential dynamics of oocyte development and provide new insights into the intra-ovarian regulatory mechanisms of ovarian development and oocyte maturation in H. labeo. These findings may be important for research on improving egg quality and reproduction in aquaculture.

Precision miRNA profiling: Electrochemiluminescence powered by CRISPR-Cas13a and hybridization chain reaction.

The article details a groundbreaking platform for detecting microRNAs (miRNAs), crucial biomolecules involved in gene regulation and linked to various diseases. This innovative platform combines the CRISPR-Cas13a system's precise ability to specifically target and cleave RNA molecules with the amplification capabilities of the hybridization chain reaction (HCR). HCR aids in signal enhancement by creating branched DNA structures. Additionally, the platform employs electrochemiluminescence (ECL) for detection, noted for its high sensitivity and low background noise, making it particularly effective. A key application of this technology is in the detection of miR-17, a biomarker associated with multiple cancer types. It exhibits remarkable detection capabilities, characterized by low detection limits (14.38 aM) and high specificity. Furthermore, the platform's ability to distinguish between similar miRNA sequences and accurately quantify miR-17 in cell lysates underscores its significant potential in clinical and biomedical fields. This combination of precise targeting, signal amplification, and sensitive detection positions the platform as a powerful tool for miRNA analysis in medical diagnostics and research.

Long-Range Structural Order in a Hidden Phase of Ruddlesden-Popper Bilayer Nickelate La3Ni2O7.

The recent discovery of superconductivity in the Ruddlesden-Popper bilayer nickelate, specifically La3Ni2O7, has generated significant interest in the exploration of high-temperature superconductivity within this material family. In this study, we present the crystallographic and electrical resistivity properties of two distinct Ruddlesden-Popper nickelates: the bilayer La3Ni2O7 (referred to as 2222-phase) and a previously uncharacterized phase, La3Ni2O7 (1313-phase). The 2222-phase is characterized by a pseudo F-centered orthorhombic lattice, featuring bilayer perovskite [LaNiO3] layers interspaced by rock salt [LaO] layers, forming a repeated ...2222... sequence. Intriguingly, the 1313-phase, which displays semiconducting properties, crystallizes in the Cmmm space group and exhibits a pronounced predilection for a C-centered orthorhombic lattice. Within this structure, the perovskite [LaNiO3] layers exhibit a distinctive long-range ordered arrangement, alternating between single- and trilayer configurations, resulting in a ...1313... sequence. This report contributes to novel insights into the crystallography and the structure-property relationship of Ruddlesden-Popper nickelates, paving the way for further investigations into their unique physical properties.

RNA-seq revealed the anti-pyroptotic effect of suramin by suppressing NLRP3/caspase-1/GSDMD pathway in LPS-induced MH-S alveolar macrophages.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), acting as one common sepsis-associated organ injury, induces uncontrolled and self-amplifies pulmonary inflammation. Given the lack of clinically effective approaches, the mortality rate of it still remains high. Suramin(SUR), as an antiparasitic drug initially, was found to ameliorate sepsis associated ALI in our previous work. However, the underlying mechanism of its protective effects has not been clarified. Pyroptosis, categorized as an inflammatory form of programmed cell death, could aggravate lung inflammatory responses via inducing alveolar macrophages (AM) pyroptosis. METHODS: MH-S AM cell line was stimulated with or without lipopolysaccharide (LPS) or suramin, and the differential expression genes (DEGs) were excavated using RNA sequencing (RNA-seq). To identify the regulatory roles of these genes, pyroptosis-related genes (PRGs), GO/KEGG and GSEA analysis were conducted. We also performed WB, qRTPCR and ELISA to validate the RNA-seq results and further expound the protective effect of suramin. RESULTS: 624 DEGs were identified between control (CON) and lipopolysaccharide (LPS) groups, and enrichment analysis of these genes revealed significantly enriched pathways that related to immune system and signal transduction. Meanwhile, 500 DEGs were identified in LPS/SUR+LPS group. In addition to the pathways mentioned above, IL-17 pathway and C-type lectin receptor signaling pathway were also enriched. All 6 pathways were connected with pyroptosis. Concurrently, the "DESeq2" R package was used to identify differentially expressed PRGs. Nod1, Nod2, interleukin (IL)-1b, IL-6, tumor necrosis factor (TNF), NLRP3 were upregulated under LPS stimulation. Then, in SUR+LPS group, Nod2, IL-6, IL-1b, NLRP3 were downregulated. The validation results of WB, qRT-PCR, and ELISA showed: the protein and mRNA expression levels of NLRP3, caspase-1, GSDMD and the concentrations of IL-1b, IL-18 were decreased when treated with suramin and LPS. CONCLUSION: Suramin could inhibit NLRP3/caspase-1/GSDMD canonical pyroptosis pathway in LPS-induced MH-S alveolar macrophages.

Modification of spin-ice physics in Ho2Ti2O7 thin films.

We present an extensive study on the effect of substrate orientation, strain, stoichiometry, and defects on spin-ice physics in Ho2Ti2O7 thin films grown onto yttria-stabilized-zirconia substrates. We find that growth in different orientations produces different strain states in the films. All films exhibit similar c-axis lattice parameters for their relaxed portions, which are consistently larger than the bulk value of 10.1 Å. Transmission electron microscopy reveals antisite disorder and growth defects to be present in the films, but evidence of stuffing is not observed. The amount of disorder depends on the growth orientation, with the (110) film showing the least. Magnetization measurements at 1.8 K show the expected magnetic anisotropy and saturation magnetization values associated with a spin ice for all orientations; shape anisotropy is apparent when comparing in- and out-of-plane directions. Significantly, only the (110)-oriented films display the hallmark spin-ice plateau state in magnetization, albeit less well defined compared to the plateau observed in a single crystal. Neutron-scattering maps on the more disordered (111)-oriented films show the Q=0 phase previously observed in bulk materials, but the Q=X phase giving the plateau state remains elusive. We conclude that the spin-ice physics in thin films is modified by defects and strain, leading to a reduction in the temperature at which correlations drive the system into the spin-ice state.