To investigate the effect of molecular hydrogen (H2) in a rat model subjected to optic nerve crush (ONC).
We tested the hypothesis that after optic nerve crush (ONC), retinal ganglion cell (RGC) ...could be protected by H₂. Rats in different groups received saline or hydrogen-rich saline every day for 14 days after ONC. Retinas from animals in each group underwent measurements of hematoxylin and eosin (H&E) staining, cholera toxin beta (CTB) tracing, gamma synuclein staining, and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining 2 weeks post operation. Flash visual evoked potentials (FVEP) and pupillary light reflex (PLR) were then tested to evaluate the function of optic nerve. The malondialdehyde (MDA) level in retina was evaluated.
H&E, gamma synuclein staining and CTB tracing showed that the survival rate of RGCs in hydrogen saline-treated group was significantly higher than that in saline-treated group. Apoptosis of RGCs assessed by TUNEL staining were less observed in hydrogen saline-treated group. The MDA level in retina of H₂ group was much lower than that in placebo group. Furthermore, animals treated with hydrogen saline showed better function of optic nerve in assessments of FVEP and PLR.
These results demonstrated that H₂ protects RGCs and helps preserve the visual function after ONC and had a neuroprotective effect in a rat model subjected to ONC.
Breast cancer is a kind of common female cancers. Increasing evidence has exhibited that lncRNAs exert a crucial role in breast cancer. So far, the mechanism of lncRNAs in breast cancer is still not ...well established. In our current study, we focused on the biological role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in breast cancer. We observed that NEAT1 levels were significantly increased in human breast cancer cells including MCF‐7, MDA‐MB‐453, MDA‐MB‐231, and SKBR3 cells compared to normal mammary epithelial cells MCF‐10A while miR‐448 was decreased. We found that downregulation of NEAT1 was able to inhibit the growth of breast cancer cells and miR‐448 mimic exerted the similar function. Bioinformatics analysis and dual luciferase reporter assays confirmed the negative correlation between NEAT1 and miR‐448 in vitro. In addition, ZEB1 was predicted as a novel mRNA target of miR‐448. Overexpression of NEAT1 can induce breast cancer cell growth, migration, and invasion by inhibiting miR‐448 and upregulating ZEB1. It was demonstrated that NEAT1 can increase ZEB1 levels while miR‐448 mimic can repress ZEB1. It was speculated in our study that NEAT1 can serve as a competing endogenous lncRNA (ceRNA) to modulate ZEB1 by sponging miR‐448 in breast cancer. To conclude, we uncovered that NEAT1 participated in breast cancer progression by regulating miR‐448 and ZEB1. NEAT1 can be provided as a vital biomarker in breast cancer diagnosis and treatment therapy.
Our results implied that NEAT1 can play a significant role in breast cancer progression. We observed that NEAT1 downregulation could inhibit breast cancer progression. In addition, a reverse correlation between NEAT1 and miR‐448 was validated in our research, and ZEB1was concentrated on in our investigation asit can be targeted by miR‐448.
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 ...dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease. SARS-CoV-2-infected ferrets exhibit elevated body temperatures and virus replication. Although fatalities were not observed, SARS-CoV-2-infected ferrets shed virus in nasal washes, saliva, urine, and feces up to 8 days post-infection. At 2 days post-contact, SARS-CoV-2 was detected in all naive direct contact ferrets. Furthermore, a few naive indirect contact ferrets were positive for viral RNA, suggesting airborne transmission. Viral antigens were detected in nasal turbinate, trachea, lungs, and intestine with acute bronchiolitis present in infected lungs. Thus, ferrets represent an infection and transmission animal model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines.
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•SARS-CoV-2-infected ferrets exhibit elevated body temperature and virus replication•SARS-CoV-2 is shed in nasal washes, saliva, urine and feces•SARS-CoV-2 is effectively transmitted to naive ferrets by direct contact•SARS-CoV-2 infection leads acute bronchiolitis in infected ferrets
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spreads, leading to a pandemic infection. Kim et al. show that ferrets are highly susceptible to SARS-CoV-2 infection and effectively transmit the virus by direct or indirect contact, recapitulating human infection and transmission.
Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has greatly improved the clinical efficacy of malignant tumor therapy. ICI-mediated antitumor responses depend on the infiltration ...of T cells capable of recognizing and killing tumor cells. ICIs are not effective in "cold tumors", which are characterized by the lack of T-cell infiltration. To realize the full potential of immunotherapy and solve this obstacle, it is essential to understand the drivers of T-cell infiltration into tumors. We present a critical review of our understanding of the mechanisms underlying "cold tumors", including impaired T-cell priming and deficient T-cell homing to tumor beds. "Hot tumors" with significant T-cell infiltration are associated with better ICI efficacy. In this review, we summarize multiple strategies that promote the transformation of "cold tumors" into "hot tumors" and discuss the mechanisms by which these strategies lead to increased T-cell infiltration. Finally, we discuss the application of nanomaterials to tumor immunotherapy and provide an outlook on the future of this emerging field. The combination of nanomedicines and immunotherapy enhances cross-presentation of tumor antigens and promotes T-cell priming and infiltration. A deeper understanding of these mechanisms opens new possibilities for the development of multiple T cell-based combination therapies to improve ICI effectiveness.
Layered transition metal oxides have drawn much attention as a promising candidate cathode material for sodium‐ion batteries. However, their performance degradation originating from strains and ...lattice phase transitions remains a critical challenge. Herein, a high‐concentration Zn‐substituted NaxMnO2 cathode with strongly suppressed P2–O2 transition is investigated, which exhibits a volume change as low as 1.0% in the charge/discharge process. Such ultralow strain characteristics ensure a stable host for sodium ion storage, which significantly improves the cycling stability and rate capability of the cathode material. Also, the strong coupling between the highly reversible capacity and the doping content of Zn in NaxMnO2 is investigated. It is suggested that a reversible anionic redox reaction can be effectively triggered by Zn ions and is also highly dependent on the Zn content. Such an ion doping strategy could shed light on the design and construction of stable and high‐capacity sodium ion host.
A high‐concentration Zn‐substituted P2‐type is found to exhibit ultralow strain characteristics as a high‐performance sodium‐ion battery cathode. In the sodiation/desodiation process, this P2‐Na2/3Zn0.25Mn0.75O2 exhibits a near zero strain extending along the c‐direction (0.8%) and a small change in volume (1.0%), which significantly improves the cycling stability and rate capability of the cathode material.
Various kinds of amorphous materials, such as transition metal dichalcogenides, metal oxides, and metal phosphates, have demonstrated superior electrocatalytic performance compared with their ...crystalline counterparts. Compared to other materials for electrocatalysis, noble metals exhibit intrinsically high activity and excellent durability. However, it is still very challenging to prepare amorphous noble‐metal nanomaterials due to the strong interatomic metallic bonding. Herein, the discovery of a unique thiol molecule is reported, namely bismuthiol I, which can induce the transformation of Pd nanomaterials from face‐centered‐cubic (fcc) phase into amorphous phase without destroying their integrity. This ligand‐induced amorphization is realized by post‐synthetic ligand exchange under ambient conditions, and is applicable to fcc Pd nanomaterials with different capping ligands. Importantly, the obtained amorphous Pd nanoparticles exhibit remarkably enhanced activity and excellent stability toward electrocatalytic hydrogen evolution in acidic solution. This work provides a facile and effective method for preparing amorphous Pd nanomaterials, and demonstrates their promising electrocatalytic application.
A unique thiol molecule, namely bismuthiol I, is discovered, which can induce the amorphization of Pd nanomaterials by ligand exchange under ambient conditions. This method is applicable to different kinds of Pd nanomaterials without destroying their integrity. Notably, the obtained amorphous Pd nanoparticles show dramatically enhanced electrocatalytic activity and excellent durability toward the hydrogen evolution reaction.
Radiotherapy is an important therapeutic strategy for cancer treatment through direct damage to cancer cells and augmentation of antitumor immune responses. However, the efficacy of radiotherapy is ...limited by hypoxia-mediated radioresistance and immunosuppression in tumor microenvironment. Here, we construct a stabilized theranostic nanoprobe based on quantum dots emitting in the near-infrared IIb (NIR-IIb, 1,500-1,700 nm) window modified by catalase, arginine-glycine-aspartate peptides and poly(ethylene glycol). We demonstrate that the nanoprobes effectively aggregate in the tumor site to locate the tumor region, thereby realizing precision radiotherapy with few side-effects. In addition, nanoprobes relieve intratumoral hypoxia and reduce the tumor infiltration of immunosuppressive cells. Moreover, the nanoprobes promote the immunogenic cell death of cancer cells to trigger the activation of dendritic cells and enhance T cell-mediated antitumor immunity to inhibit tumor metastasis. Collectively, the nanoprobe-mediated immunogenic radiotherapy can boost the abscopal effect to inhibit tumor metastasis and prolong survival.
•ACE-inhibitory activity is related to the degree of enzymatic hydrolysis and peptide sequence.•Optimal hydrolysis enzymes for animal products are pepsin, trypsin and chymotrypsin.•Optimal hydrolysis ...enzymes for marine organisms and plants are alcalase, neutrase and thermolysin.•ACE-inhibitory peptides are composed of hydrophobic amino acids at the N-terminus and proline.
Bioactive peptides from food proteins exert beneficial effects on human health, such as angiotensin-converting enzyme (ACE) inhibition and antihypertensive activity. Several studies have reported that ACE-inhibitory peptides can come from animal products, marine organisms, and plants—derived by hydrolyzing enzymes such as pepsin, chymotrypsin, and trypsin—and microbial enzymes such as alcalase, thermolysin, flavourzyme, and proteinase K. Different ACE-inhibitory effects are closely related with different peptide sequences and molecular weights. Sequences of ACE-inhibitory peptides are composed of hydrophobic (proline) and aliphatic amino acids (isoleucine and leucine) at the N-terminus. As result of this review, we assume that low molecular weight peptides have a greater ACE inhibition because lower molecular weight peptides have a higher absorbency in the body. Therefore, the ACE-inhibitory effect is closely related with the degree of enzymatic hydrolysis and the composition of the peptide sequence.
Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal ...cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to the development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.
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