Injectable Hydrogel To Deliver Bone Mesenchymal Stem Cells Preloaded with Azithromycin To Promote Spinal Cord Repair.

Spinal cord injury is a disease that causes severe damage to the central nervous system. Currently, there is no cure for spinal cord injury. Azithromycin is commonly used as an antibiotic, but it can also exert anti-inflammatory effects by down-regulating M1-type macrophage genes and up-regulating M2-type macrophage genes, which may make it effective for treating spinal cord injury. Bone mesenchymal stem cells possess tissue regenerative capabilities that may help promote the repair of the injured spinal cord. In this study, our objective was to explore the potential of promoting repair in the injured spinal cord by delivering bone mesenchymal stem cells that had internalized nanoparticles preloaded with azithromycin. To achieve this objective, we formulated azithromycin into nanoparticles along with a trans-activating transcriptional activator, which should enhance nanoparticle uptake by bone mesenchymal stem cells. These stem cells were then incorporated into an injectable hydrogel. The therapeutic effects of this formulation were analyzed in vitro using a mouse microglial cell line and a human neuroblastoma cell line, as well as in vivo using a rat model of spinal cord injury. The results showed that the formulation exhibited anti-inflammatory and neuroprotective effects in vitro as well as therapeutic effects in vivo. These results highlight the potential of a hydrogel containing bone mesenchymal stem cells preloaded with azithromycin and trans-activating transcriptional activator to mitigate spinal cord injury and promote tissue repair.

Radiogenomic analysis of ultrasound phenotypic features coupled to proteomes predicts metastatic risk in primary prostate cancer.

BACKGROUND: Primary prostate cancer with metastasis has a poor prognosis, so assessing its risk of metastasis is essential. METHODS: This study combined comprehensive ultrasound features with tissue proteomic analysis to obtain biomarkers and practical diagnostic image features that signify prostate cancer metastasis. RESULTS: In this study, 17 ultrasound image features of benign prostatic hyperplasia (BPH), primary prostate cancer without metastasis (PPCWOM), and primary prostate cancer with metastasis (PPCWM) were comprehensively analyzed and combined with the corresponding tissue proteome data to perform weighted gene co-expression network analysis (WGCNA), which resulted in two modules highly correlated with the ultrasound phenotype. We screened proteins with temporal expression trends based on the progression of the disease from BPH to PPCWOM and ultimately to PPCWM from two modules and obtained a protein that can promote prostate cancer metastasis. Subsequently, four ultrasound image features significantly associated with the metastatic biomarker HNRNPC (Heterogeneous nuclear ribonucleoprotein C) were identified by analyzing the correlation between the protein and ultrasound image features. The biomarker HNRNPC showed a significant difference in the five-year survival rate of prostate cancer patients (p < 0.0053). On the other hand, we validated the diagnostic efficiency of the four ultrasound image features in clinical data from 112 patients with PPCWOM and 150 patients with PPCWM, obtaining a combined diagnostic AUC of 0.904. In summary, using ultrasound imaging features for predicting whether prostate cancer is metastatic has many applications. CONCLUSION: The above study reveals noninvasive ultrasound image biomarkers and their underlying biological significance, which provide a basis for early diagnosis, treatment, and prognosis of primary prostate cancer with metastasis.

Combined toxicities of cadmium and five agrochemicals to the larval zebrafish (Danio rerio).

Different pollutants usually co-exist in the natural environment, and the ecological and health risk assessment of agrochemicals needs to be carried out based on the combined toxicological effects of pollutants. To examine the combined toxicity to aquatic organisms, the effects of cadmium (Cd) and five pesticides (acetamiprid, carbendazim, azoxystrobin, chlorpyrifos, and bifenthrin) mixture on zebrafish (Danio rerio) larvae were assessed. The data from the 96-h toxicity test indicated that bifenthrin possessed the highest toxicity to D. rerio with the LC50 value of 0.15 mg L-1, followed by chlorpyrifos (0.36 mg L-1) and azoxystrobin (0.63 mg L-1). Cd (6.84 mg L-1) and carbendazim (8.53 mg L-1) induced the intermediate toxic responses, while acetamiprid (58.39 mg L-1) presented the lowest toxicity to the organisms. Pesticide mixtures containing chlorpyrifos and bifenthrin or acetamiprid and carbendazim showed synergistic impacts on the zebrafish. Besides, two binary combinations of Cd-acetamiprid and Cd-chlorpyrifos also displayed a synergistic effect on D. rerio. Our results offered a better idea of the mixed ecological risk assessment of Cd and different agricultural chemicals to aquatic organisms. Our findings better interpreted how the interaction between Cd and various agrochemicals changed their toxicity to aquatic vertebrates and provided valuable insights into critical impacts on the ecological hazard of their combinations.

Mixture toxicity of cadmium and acetamiprid to the early life stages of zebrafish (Danio rerio).

Aquatic organisms are often exposed to contaminants that occur in the natural environment. Nevertheless, the toxic effects of chemical combinations on aquatic animals and their underlying toxic mechanisms for dealing with such exposures are still not fully understood. In this study, we investigated the combined effects of cadmium (Cd) and acetamiprid (ACE) on zebrafish (Danio rerio) using various endpoints. Cd exhibited a 96-h LC50 value of 4.77 mg a.i. L-1 against zebrafish embryos, which was lower than that of ACE (152.6 mg a.i. L-1). In contrast, the 96-h LC50 value of the mixture of Cd and ACE was 157.4 mg a.i. L-1. The mixture of Cd and ACE had a synergetic effect on the organisms. The activities of T-SOD, POD, and CarE were significantly changed in most exposures compared with the control group. In addition, five genes (TRα, crh, Tnf, IL, and P53) involved in oxidative stress, cellular apoptosis, the immune system, and the endocrine system exhibited more remarkable changes when exposed to chemical mixtures relative to their individual counterparts, demonstrating variations in the cellular and mRNA expression levels induced by the mixture exposure of ACE and Cd during the embryonic development of zebrafish. Therefore, these results indicated that the combined pollution of ACE and Cd could be a potentially hazardous factor, and further investigation is necessary for the safety evaluation and application of ACE. Moreover, further investigation on the combined toxicities of various chemicals must be performed to determine the chemical mixtures with synergistic responses.

CAQK modification enhances the targeted accumulation of metformin-loaded nanoparticles in rats with spinal cord injury.

Spinal cord injury (SCI) often causes neuronal membrane rupture and immediate death of neurons, followed by complicated secondary injuries. Treatment of SCI still remains a major challenge in clinical practice; thus, a great advance is urgently needed in this field. Metformin (MET) has anti-oxidant, anti-inflammatory, anti-apoptotic and neuroprotective properties, which may exert a potential therapeutic effect on SCI. In this study, we established a zein-based MET-loaded nanodrug system (CAQK-MET-NPs) for the targeted drug delivery for SCI. The results showed that MET could be effectively encapsulated into zein to obtain the zein-based spherical nanoparticles. Pharmacokinetic analysis indicated that CAQK-MET-NPs exhibited sustained-release and long-term therapeutic effects. The fluorescence imaging and tissue distribution experiments showed that CAQK-MET-NPs could efficiently accumulate at the lesion site of SCI rats. In conclusion, CAQK-MET-NPs may be a promising nanodrug for the treatment of SCI.

Label-Free Virtual HER2 Immunohistochemical Staining of Breast Tissue using Deep Learning.

The immunohistochemical (IHC) staining of the human epidermal growth factor receptor 2 (HER2) biomarker is widely practiced in breast tissue analysis, preclinical studies, and diagnostic decisions, guiding cancer treatment and investigation of pathogenesis. HER2 staining demands laborious tissue treatment and chemical processing performed by a histotechnologist, which typically takes one day to prepare in a laboratory, increasing analysis time and associated costs. Here, we describe a deep learning-based virtual HER2 IHC staining method using a conditional generative adversarial network that is trained to rapidly transform autofluorescence microscopic images of unlabeled/label-free breast tissue sections into bright-field equivalent microscopic images, matching the standard HER2 IHC staining that is chemically performed on the same tissue sections. The efficacy of this virtual HER2 staining framework was demonstrated by quantitative analysis, in which three board-certified breast pathologists blindly graded the HER2 scores of virtually stained and immunohistochemically stained HER2 whole slide images (WSIs) to reveal that the HER2 scores determined by inspecting virtual IHC images are as accurate as their immunohistochemically stained counterparts. A second quantitative blinded study performed by the same diagnosticians further revealed that the virtually stained HER2 images exhibit a comparable staining quality in the level of nuclear detail, membrane clearness, and absence of staining artifacts with respect to their immunohistochemically stained counterparts. This virtual HER2 staining framework bypasses the costly, laborious, and time-consuming IHC staining procedures in laboratory and can be extended to other types of biomarkers to accelerate the IHC tissue staining used in life sciences and biomedical workflow.

TAT-modified tetramethylpyrazine-loaded nanoparticles for targeted treatment of spinal cord injury.

Tetramethylpyrazine (TMP) has been effectively used for treating spinal cord injury (SCI) due to its anti-inflammatory, antioxidant, and neuroprotective activity. However, its clinical application is limited due to poor water solubility and insufficient spinal cord targeting through the traditional dosage forms. Given that intravascular neutrophils are quickly recruited to the injury site as part of the inflammatory response in SCI, we conjugated the cell-penetrating HIV trans-activator of transcription (TAT) peptide to human serum albumin nanoparticles (NPs) to make a TMP delivery system (TAT-TMP-NPs) that could be internalized by neutrophils and delivered to SCI lesions. Results found that in SCI rats TAT-TMP-NPs promoted the recovery of locomotor function and the lesion area, while reducing the levels of inflammatory cytokines and oxidative stress-related factors. Safety evaluation and in vivo small-animal imaging showed that the cell-penetrating peptide TAT could enhance the uptake of TAT-TMP-NPs by neutrophils without being toxic to the body. TAT-TMP-NPs may overcome the poor water solubility and low bioavailability of TMP, showing promise for the clinical treatment of SCI.

TAT-modified serum albumin nanoparticles for sustained-release of tetramethylpyrazine and improved targeting to spinal cord injury.

BACKGROUND: Spinal Cord injury (SCI) is a kind of severe traumatic disease. The inflammatory response is a significant feature after SCI. Tetramethylpyrazine (TMP), a perennial herb of umbelliferae, is an alkaloid extracted from ligustici. TMP can inhibit the production of nitric oxide and reduce the inflammatory response in peripheral tissues. It can be seen that the therapeutic effect of TMP on SCI is worthy of affirmation. TMP has defects such as short half-life and poor water-solubility. In addition, the commonly used dosage forms of TMP include tablets, dropping pills, injections, etc., and its tissue and organ targeting is still a difficult problem to solve. To improve the solubility and targeting of TMP, here, we developed a nanotechnology-based drug delivery system, TMP-loaded nanoparticles modified with HIV trans-activator of transcription (TAT-TMP-NPs). RESULTS: The nanoparticles prepared in this study has integrated structure. The hemolysis rate of each group is less than 5%, indicating that the target drug delivery system has good safety. The results of in vivo pharmacokinetic studies show that TAT-TMP-NPs improves the bioavailability of TMP. The quantitative results of drug distribution in vivo show that TAT-TMP-NPs is more distributed in spinal cord tissue and had higher tissue targeting ability compared with other treatment groups. CONCLUSIONS: The target drug delivery system can overcome the defect of low solubility of TMP, achieve the targeting ability, and show the further clinical application prospect.

A New Image Encryption Algorithm Based on Composite Chaos and Hyperchaos Combined with DNA Coding.

In order to obtain chaos with a wider chaotic scope and better chaotic behavior, this paper combines the several existing one-dimensional chaos and forms a new one-dimensional chaotic map by using a modular operation which is named by LLS system and abbreviated as LLSS. To get a better encryption effect, a new image encryption method based on double chaos and DNA coding technology is proposed in this paper. A new one-dimensional chaotic map is combined with a hyperchaotic Qi system to encrypt by using DNA coding. The first stage involves three rounds of scrambling; a diffusion algorithm is applied to the plaintext image, and then the intermediate ciphertext image is partitioned. The final encrypted image is formed by using DNA operation. Experimental simulation and security analysis show that this algorithm increases the key space, has high sensitivity, and can resist several common attacks. At the same time, the algorithm in this paper can reduce the correlation between adjacent pixels, making it close to 0, and increase the information entropy, making it close to the ideal value and achieving a good encryption effect.

IL-4 Gene Polymorphism May Contribute to an Increased Risk of Atopic Dermatitis in Children.

UNLABELLED: This study aimed to elucidate the associations between interleukin-4 (IL-4) single nucleotide polymorphisms (SNPs), 590C/T and 589C/T, serum IL-4 levels, and atopic dermatitis (AD) in children. METHODS: A total of 82 children with AD were randomly selected as the case group and divided into mild group (15 cases), moderate group (46 cases), and severe group (21 cases). Additionally, 100 healthy children were selected as the control group. Genotype frequencies of IL-4 SNPs were detected by PCR-RFLP. Serum IL-4 levels were measured by ELISA. RESULTS: Significant differences were shown in genotype distributions and allele frequencies of 589C/T and allele frequencies of 590C/T (all P < 0.05). Serum IL-4 levels in the mild, moderate, and severe groups were significantly higher than those in the control group; significant differences were found among these three groups with increased severity of AD. Serum IL-4 levels of heterozygote and mutant homozygote carriers in the mild, moderate, and severe groups were higher than wild homozygote carriers in those three groups and the control group (all P < 0.05). CONCLUSION: 590T and 589T alleles of IL-4 gene may be associated with high levels of serum IL-4, which may increase the risk of AD in children.

Physiological investigation of gold nanorods toward watermelon.

The objective of the present study was to evaluate the phytotoxicity and oxidant stress of the gold nanorods toward watermelon, and hence give a quantitative risk assessment of both seeds and plants phase. The seed germination, the activity of antioxidant enzymes, and the contents of soluble protein and malondialdehyde (MDA) have been measured while the plant roots were observed by transmission electron microscopy (TEM). It was found that the gold nanorods significantly promoted the root elongation. Furthermore, the results on the enzymes activities of plant indicated that oxidative stress happened in the plant treated with gold nanorods. However, the gold nanorods resulted in the phytotoxicity toward plant especially at high concentration. The TEM images of the plant roots with and without the treatment of gold nanorods showed the significant different size of starch granules. In conclusion, significant physiological changes of plant occurred after treatment with the gold nanorods.