Mated-Atom Nanozymes with Efficient Assisted NAD+ Replenishment for Skin Regeneration.

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.

SUMOylation of the ubiquitin ligase IDOL decreases LDL receptor levels and is reversed by SENP1.

Inducible degrader of the low-density lipoprotein receptor (IDOL) is an E3 ubiquitin ligase mediating degradation of low-density lipoprotein (LDL) receptor (LDLR). IDOL also controls its own stability through autoubiquitination, primarily at lysine 293. Whether IDOL may undergo other forms of posttranslational modification is unknown. In this study, we show that IDOL can be modified by small ubiquitin-like modifier 1 at the K293 residue at least. The SUMOylation of IDOL counteracts its ubiquitination and augments IDOL protein levels. SUMOylation and the associated increase of IDOL protein are effectively reversed by SUMO-specific peptidase 1 (SENP1) in an activity-dependent manner. We further demonstrate that SENP1 affects LDLR protein levels by modulating IDOL. Overexpression of SENP1 increases LDLR protein levels and enhances LDL uptake in cultured cells. On the contrary, loss of SENP1 lowers LDLR levels in an IDOL-dependent manner and reduces LDL endocytosis. Collectively, our results reveal SUMOylation as a new regulatory posttranslational modification of IDOL and suggest that SENP1 positively regulates the LDLR pathway via deSUMOylation of IDOL and may therefore be exploited for the treatment of cardiovascular disease.

Equus roundworms (Parascaris univalens) are undergoing rapid divergence while genes involved in metabolic as well as anthelminic resistance are under positive selection.

BACKGROUND: The evolution of parasites is often directly affected by the host's environment. Studies on the evolution of the same parasites in different hosts are of great interest and are highly relevant to our understanding of divergence. METHODS: Here we performed whole-genome sequencing of Parascaris univalens from different Equus hosts (horses, zebras and donkeys). Phylogenetic and selection analyses were performed to study the divergence and adaptability of P. univalens. RESULTS: At the genetic level, multiple lines of evidence indicate that P. univalens is mainly separated into two clades (horse-derived and zebra & donkey-derived). This divergence began 300-1000 years ago, and we found that most of the key enzymes related to glycolysis were under strong positive selection in zebra & donkey-derived roundworms, whereas the lipid-related metabolic system was under positive selection in horse-derived roundworms, indicating that the adaptive evolution of metabolism has occurred over the past few centuries. In addition, we found that some drug-related genes showed a significantly higher degree of selection in diverse populations. CONCLUSIONS: This work reports the adaptive evolution and divergence trend of P. univalens in different hosts for the first time. Its results indicate that the divergence of P. univalens is a continuous, dynamic process. Furthermore, the continuous monitoring of the effects of differences in nutritional and drug histories on the rapid evolution of roundworms is conducive to further understanding host-parasite interactions.

Biomineralization-inspired magnetic nanoflowers for sensitive miRNA detection based on exonuclease-assisted target recycling amplification.

Biomineralization-inspired magnetic hybrid nanoflowers were prepared facilely, and capture probes were easily immobilized on the obtained nanoflowers without tedious processing. Based on the magnetic hybrid nanoflowers and exonuclease-assisted target recycling amplification, a fluorescence miRNA sensor was fabricated. The presence of target miRNA leads to the formation of the double-strand structure, which would then be selectively digested by the exonuclease and increase fluorescence intensity. The target miRNA can be released for recycling and signal amplification. Under optimized reaction conditions, the hybrid nanoflower-based miRNA sensor had a broad detection range from 0.001 nM to 100 nM and a limit of detection of 0.23 pM (S/N = 3). The sensitive detection of miRNA in serum was also achieved with recoveries from 94.3% to 116.1%. This work provides a new insight into the fabrication of bioconjugated materials and shows great potential in miRNA sensing.

Atomic Engineering of Clusterzyme for Relieving Acute Neuroinflammation through Lattice Expansion.

Natural enzymes are efficient and versatile biocatalysts but suffer in their environmental tolerance and catalytic stability. As artificial enzymes, nanozymes can improve the catalytic stability, but it is still a challenge to achieve high catalytic activity. Here, we employed atomic engineering to build the artificial enzyme named Au24Ag1 clusterzyme that hosts an ultrahigh catalytic activity as well as strong physiological stability via atom manipulation. The designed Au24Ag1 clusterzyme activates the Ag-S active site via lattice expansion in the oligomer atom layer, showing an antioxidant property 72 times higher than that of natural antioxidant Trolox. Enzyme-mimicked studies find that Au24Ag1 clusterzyme exhibits high catalase-like (CAT-like) and glutathione peroxidase-like (GPx-like) activity with a maximum reaction rate of 68.9 and 17.8 µM/min, respectively. Meanwhile, the unique catalytic landscape exhibits distinctive reactions against inflammation by inhibiting the cytokines at an early stage in the brain. Atomic engineering of clusterzymes provides a powerful and attractive platform with satisfactory atomic dispersion for tailoring biocatalysts freely at the atomic level.

Alteration of lipid profile in subclinical hypothyroidism: a meta-analysis.

BACKGROUND: Previous studies yielded controversial results about the alteration of lipid profiles in patients with subclinical hypothyroidism. We performed a meta-analysis to investigate the association between subclinical hypothyroidism and lipid profiles. MATERIAL AND METHODS: We searched PubMed, Cochrane Library, and China National Knowledge Infrastructure articles published January 1990 through January 2014. Dissertation databases (PQDT and CDMD) were searched for additional unpublished articles. We included articles reporting the relationship between subclinical hypothyroidism and at least 1 parameter of lipid profiles, and calculated the overall weighted mean difference (WMD) with a random effects model. Meta-regression was used to explore the source of heterogeneity among studies, and the Egger test, Begg test, and the trim and fill method were used to assess potential publication bias. RESULTS: Sixteen observational studies were included in our analysis. Meta-analysis suggested that the serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and total triglyceride levels were significantly increased in patients with subclinical hypothyroidism compared with euthyroidism individuals; the WMD were 12.17 mg/dl, 7.01 mg/dl, and 13.19 mg/dl, respectively (P<0.001 for all). No significant difference was observed for serum high-density lipoprotein cholesterol (HDL-C). Match strategy was the main source of heterogeneity among studies in TC and LDL-C analysis. Potential publication bias was found in TC and LDL-C analysis by the Egger test or Begg test and was not confirmed by the trim and fill method. CONCLUSIONS: Subclinical hypothyroidism may correlate with altered lipid profile. Previous studies had limitations in the control of potential confounding factors and further studies should consider those factors.

A Nanozyme-Based Electrode for High-Performance Neural Recording.

Implanted neural electrodes have been widely used to treat brain diseases that require high sensitivity and biocompatibility at the tissue-electrode interface. However, currently used clinical electrodes cannot meet both these requirements simultaneously, which hinders the effective recording of electronic signals. Herein, nanozyme-based neural electrodes incorporating bioinspired atomically precise clusters are developed as a general strategy with a heterogeneous design for multiscale and ultrasensitive neural recording via quantum transport and biocatalytic processes. Owing to the dual high-speed electronic and ionic currents at the electrode-tissue interface, the impedance of nanozyme electrodes is 26 times lower than that of state-of-the-art metal electrodes, and the acquisition sensitivity for the local field potential is ≈10 times higher than that of clinical PtIr electrodes, enabling a signal-to-noise ratio (SNR) of up to 14.7 dB for single-neuron recordings in rats. The electrodes provide more than 100-fold higher antioxidant and multi-enzyme-like activities, which effectively decrease 67% of the neuronal injury area by inhibiting glial proliferation and allowing sensitive and stable neural recording. Moreover, nanozyme electrodes can considerably improve the SNR of seizures in acute epileptic rats and are expected to achieve precise localization of seizure foci in clinical settings.

Does enteral immune nutrition (EIN) boost the immunity of gastric cancer (GC) patients undergoing surgery? A systematic review and meta-analysis.

Introduction: The main components of enteral immunonutrition (EIN) are ω-3 fatty acids, glutamine, arginine, and nucleotide, which primarily raises the immunity of the host and helps to reduce postoperative infections and non-infectious difficulties. Although the potential benefits of EIN are widely reported, some researchers did not find it to be of much help, and hence valid conclusions about its role are still unclear. Aim: To evaluate the role of enteral immunonutrition on patients undergoing surgery for gastric cancer (GC). Material and methods: Appropriate articles were searched from the PubMed, Medline, and Central databases using the appropriate keywords as per the PRISMA guidelines. Randomized controlled trials, and retrospective, prospective, and open-label studies were included as per the predefined PICOS criteria. Demographic summary and event data for the effect of EIN on patients undergoing surgery for GC were extracted from the included studies. Results: Twelve randomized controlled clinical trials with a total of 10,422 gastric cancer patients were included. We found the odds ratio value of 0.23 (95% CI: 0.09-0.59). The results are heterogeneous with a τ2 value of 2.77, a χ2 value of 1707.96, a df value of 11, an I2 value of 99%, a z value of 3.04, and a p-value of less than 0.05. The risk ratio is 0.47 (95% CI: 0.29-0.77) with heterogeneity of τ2 value of 0.73, χ2 value of 1428.34, df value of 11, I2 value of 99%, z value of 2.99, and p-value < 0.05. Conclusions: The present meta-analysis strongly commends the use of EIN to boost the immunity of gastric cancer (GC) patients undergoing gastrectomy.

Modulation of the biocatalytic activity and selectivity of CeO2 nanozymes via atomic doping engineering.

Artificial enzymes show prospects in biomedical applications due to their stable enzymatic catalytic activity and ease of preparation. CeO2 nanozymes represent a versatile platform showing multiple enzyme-mimicking activities, although their biocatalytic activities and selectivity are relatively poor for biomedical use. Herein, we developed Mn- and Co-doped CeO2 nanozymes (M/CeO2, M = Mn or Co) via atomic engineering to achieve a significant increase in enzyme-like activity. The M/CeO2 nanozymes exhibited outstanding peroxidase-like activity with a reaction rate about 8-10 times higher than that of CeO2. Importantly, the Co/CeO2 nanozyme preferred for catalase-like activity with a 4-6-fold higher catalytic rate than CeO2, while the Mn/CeO2 nanozyme had a predilection for improving the superoxide dismutase-like capacity. This indicated the selective modulation of enzyme-mimicking activities via atomic doping engineering. Cellular level experiments revealed the in vitro therapeutic effects of the nanozymes. Mn/CeO2 and Co/CeO2 selectively modulated the intracellular redox imbalance in lipopolysaccharide (LPS)- or H2O2-stimulated nerve cells and improved cell survival. This work provides a feasible strategy for the design of catalytically selective artificial enzymes and facilitates the widespread application of CeO2 nanozymes in redox-related diseases.

Chromosome-scale genomes reveal genomic consequences of inbreeding in the South China tiger: A comparative study with the Amur tiger.

The South China tiger (Panthera tigris amoyensis, SCT) is the most critically endangered subspecies of tiger due to functional extinction in the wild. Inbreeding depression is observed among the captive population descended from six wild ancestors, resulting in high juvenile mortality and low reproduction. We assembled and characterized the first SCT genome and an improved Amur tiger (P. t. altaica, AT) genome named AmyTig1.0 and PanTig2.0. The two genomes are the most continuous and comprehensive among any tiger genomes yet reported at the chromosomal level. By using the two genomes and resequencing data of 15 SCT and 13 AT individuals, we investigated the genomic signature of inbreeding depression of the SCT. The results indicated that the effective population size of SCT experienced three phases of decline, ~5.0-1.0 thousand years ago, 100 years ago, and since captive breeding in 1963. We found 43 long runs of homozygosity fragments that were shared by all individuals in the SCT population and covered a total length of 20.63% in the SCT genome. We also detected a large proportion of identical-by-descent segments across the genome in the SCT population, especially on ChrB4. Deleterious nonsynonymous single nucleotide polymorphic sites and loss-of-function mutations were found across genomes with extensive potential influences, despite a proportion of these loads having been purged by inbreeding depression. Our research provides an invaluable resource for the formulation of genetic management policies for the South China tiger such as developing genome-based breeding and genetic rescue strategy.

Single-atom nanozymes catalytically surpassing naturally occurring enzymes as sustained stitching for brain trauma.

Regenerable nanozymes with high catalytic stability and sustainability are promising substitutes for naturally-occurring enzymes but are limited by insufficient and non-selective catalytic activities. Herein, we developed single-atom nanozymes of RhN4, VN4, and Fe-Cu-N6 with catalytic activities surpassing natural enzymes. Notably, Rh/VN4 preferably forms an Rh/V-O-N4 active center to decrease reaction energy barriers and mediates a "two-sided oxygen-linked" reaction path, showing 4 and 5-fold higher affinities in peroxidase-like activity than the FeN4 and natural horseradish peroxidase. Furthermore, RhN4 presents a 20-fold improved affinity in the catalase-like activity compared to the natural catalase; Fe-Cu-N6 displays selectivity towards the superoxide dismutase-like activity; VN4 favors a 7-fold higher glutathione peroxidase-like activity than the natural glutathione peroxidase. Bioactive sutures with Rh/VN4 show recyclable catalytic features without apparent decay in 1 month and accelerate the scalp healing from brain trauma by promoting the vascular endothelial growth factor, regulating the immune cells like macrophages, and diminishing inflammation.

Chromosome-Level Genome Assembly of the Green Peafowl (Pavo muticus).

The green peafowl (Pavo muticus) is facing a high risk of extinction due to the long-term and widespread threats of poaching and habitat conversion. Here, we present a high-quality chromosome-level genome assembly of the green peafowl with high contiguity and accuracy assembled by PacBio sequencing, DNBSEQ short-read sequencing, and Hi-C sequencing technologies. The final genome size was estimated to be 1.049 Gb, whereas 1.042 Gb of the genome was assigned to 27 pseudochromosomes. The scaffold N50 length was 75.5 Mb with a complete BUSCO score of 97.6%. We identified W and Z chromosomes and validated them by resequencing 14 additional individuals. Totally, 167.04 Mb repetitive elements were identified in the genome, accounting for 15.92% of the total genome size. We predicted 14,935 protein-coding genes, among which 14,931 genes were functionally annotated. This is the most comprehensive and complete de novo assembly of the Pavo genus, and it will serve as a valuable resource for future green peafowl ecology, evolution, and conservation studies.

High-resolution 3D spatiotemporal transcriptomic maps of developing Drosophila embryos and larvae.

Drosophila has long been a successful model organism in multiple biomedical fields. Spatial gene expression patterns are critical for the understanding of complex pathways and interactions, whereas temporal gene expression changes are vital for studying highly dynamic physiological activities. Systematic studies in Drosophila are still impeded by the lack of spatiotemporal transcriptomic information. Here, utilizing spatial enhanced resolution omics-sequencing (Stereo-seq), we dissected the spatiotemporal transcriptomic changes of developing Drosophila with high resolution and sensitivity. We demonstrated that Stereo-seq data can be used for the 3D reconstruction of the spatial transcriptomes of Drosophila embryos and larvae. With these 3D models, we identified functional subregions in embryonic and larval midguts, uncovered spatial cell state dynamics of larval testis, and revealed known and potential regulons of transcription factors within their topographic background. Our data provide the Drosophila research community with useful resources of organism-wide spatiotemporally resolved transcriptomic information across developmental stages.

Robust expression and association of ZmCCA1 with circadian rhythms in maize.

In plants, the circadian clock is an endogenous mechanism that controls a wide range of biological processes. To date, as one of the key world crops, little is known about the molecular mechanism and components of the circadian clock in maize (Zea mays). In this study, we characterized the CIRCADIAN CLOCK ASSOCIATED1 gene of maize (ZmCCA1), an ortholog of CCA1 in Arabidopsis thaliana (AtCCA1). Quantitative real-time PCR analysis revealed that ZmCCA1 was expressed in leaves and stem apex meristems in a rhythmic pattern under long day and short day conditions, and its peak gene expression appeared during the morning. ZmCCA1 transcripts accumulated in all tissues evaluated, with higher levels in tassels and ears. Additionally, the expression of another photoperiod gene ZmTOC1 peaked 12 h after dawn on long days and at 10 h after dawn on short days. Subcellular localization analysis revealed that the ZmCCA1 protein is directed to the cell nucleus. Overexpression of ZmCCA1 in Arabidopsis reduced the expression levels of downstream genes, including GIGANTEA (AtGI), CONSTANS (AtCO), and FLOWERING LOCUST (AtFT), and resulted in longer hypocotyls and delayed flowering. Taken together, our data suggest that ZmCCA1 may be a core component of the circadian clock in maize.

Neonatal hyperbilirubinemia and Gly71Arg mutation of UGT1A1 gene: a Chinese case-control study followed by systematic review of existing evidence.

AIM: To determine whether the UDP-glucuronosyltransferase 1A1 gene (UGT1A1) Gly71Arg (211G>A) mutation is associated with neonatal hyperbilirubinemia. METHODS: The study consisted of two parts. The case-control study included 112 hyperbilirubinemic infants and 105 control subjects from the Fifth People's Hospital of Shenzhen. Polymerase chain reaction, restriction fragment length polymorphisms and agarose gel electrophoresis techniques were used to detect the UGT1A1 211G>A mutation. Meta-analyses was performed to assess the association between neonatal hyperbilirubinemia and UGT1A1 211G>A. RESULTS: Our case-control study revealed that the likelihood of developing neonatal hyperbilirubinemia was 2.65 times higher in the infants with the A allele in the UGT1A1 211G>A than in the infants with the G allele (95% CI, 1.60-4.39). Meta-analyses (including data from our study) revealed that UGT1A1 211G>A is associated with an increased risk of neonatal hyperbilirubinemia [odds ratio (OR), 2.37; 95% CI, 2.05-2.74]. In the subgroup analyses based on ethnicity, significantly elevated risks were found in Asian populations (OR, 2.45; 95% CI, 2.10-2.84), but no significant associations were present in Caucasian populations (OR, 1.54; 95% CI, 0.87-2.75). CONCLUSION: The UGT1A1 211G>A mutation is associated with neonatal hyperbilirubinemia in Asians, but not in Caucasians.

Association of neonatal hyperbilirubinemia with uridine diphosphate-glucuronosyltransferase 1A1 gene polymorphisms: meta-analysis.

BACKGROUND: Recent reports have suggested that genetic factors, including mutations in the coding region or promoter of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) may increase the risk of development of neonatal hyperbilirubinemia, but the relationship has not been evaluated on systematic review or meta-analysis. METHODS: A meta-analysis of observational studies reporting effect estimates and 95% confidence intervals (95%CI) was conducted on the association between UGT1A1 polymorphisms and neonatal hyperbilirubinemia. RESULTS: A total of 27 eligible studies were identified. In total, 17 studies focused on the association of neonatal hyperbilirubinemia with UGT1A1 Gly71Arg polymorphisms, which indicated that these polymorphisms were associated with an increased risk of neonatal hyperbilirubinemia (A/A+G/A vs G/G: odds ratio [OR], 2.70; P= 0.00; 95%CI: 2.22-3.29; I(2) = 0.0%; P(heterogeneity) = 0.55). Subgroup analyses by ethnicity validated this correlation in Asian, but not in Caucasian, populations (OR, 1.74; P= 0.10; 95%CI: 0.90-3.35; I(2) = 0.00%; P(heterogeneity) = 0.67). Furthermore, 18 studies focused on the association of neonatal hyperbilirubinemia with UGT1A1 TATA promoter polymorphisms. These studies concluded that TATA promoter variants were not associated with an increased risk of neonatal hyperbilirubinemia (7/7 + 6/7 vs 6/6: OR, 1.13; P= 0.23; 95%CI: 0.93-1.37; I(2) = 80.0%; P(heterogeneity) = 0.00). CONCLUSION: UGT1A1 Gly71Arg polymorphisms are a risk factor for developing neonatal hyperbilirubinemia in Asian, but not Caucasian, subjects. UGT1A1 TATA promoter polymorphisms were not associated with an increased risk of neonatal hyperbilirubinemia in Asian subjects, but results from the Caucasian population were conflicting and require further epidemiological investigation.

Catalytic patch with redox Cr/CeO2 nanozyme of noninvasive intervention for brain trauma.

Traumatic brain injury (TBI) is a sudden injury to the brain, accompanied by the production of large amounts of reactive oxygen and nitrogen species (RONS) and acute neuroinflammation responses. Although traditional pharmacotherapy can effectively decrease the immune response of neuron cells via scavenging free radicals, it always involves in short reaction time as well as rigorous clinical trial. Therefore, a noninvasive topical treatment method that effectively eliminates free radicals still needs further investigation. Methods: In this study, a type of catalytic patch based on nanozymes with the excellent multienzyme-like activity is designed for noninvasive treatment of TBI. The enzyme-like activity, free radical scavenging ability and therapeutic efficacy of the designed catalytic patch were assessed in vitro and in vivo. The structural composition was characterized by the X-ray diffraction, X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy technology. Results: Herein, the prepared Cr-doped CeO2 (Cr/CeO2) nanozyme increases the reduced Ce3+ states, resulting in its enzyme-like activity 3-5 times higher than undoped CeO2. Furthermore, Cr/CeO2 nanozyme can improve the survival rate of LPS induced neuron cells via decreasing excessive RONS. The in vivo experiments show the Cr/CeO2 nanozyme can promote wound healing and reduce neuroinflammation of mice following brain trauma. The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases. Conclusions: The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases.

Chromosome-Scale Genome of Masked Palm Civet (Paguma larvata) Shows Genomic Signatures of Its Biological Characteristics and Evolution.

The masked palm civet (Paguma larvata) is a small carnivore with distinct biological characteristics, that likes an omnivorous diet and also serves as a vector of pathogens. Although this species is not an endangered animal, its population is reportedly declining. Since the severe acute respiratory syndrome (SARS) epidemic in 2003, the public has been particularly concerned about this species. Here, we present the first genome of the P. larvata, comprising 22 chromosomes assembled using single-tube long fragment read (stLFR) and Hi-C technologies. The genome length is 2.41 Gb with a scaffold N50 of 105.6 Mb. We identified the 107.13 Mb X chromosome and one 1.34 Mb Y-linked scaffold and validated them by resequencing 45 P. larvata individuals. We predicted 18,340 protein-coding genes, among which 18,333 genes were functionally annotated. Interestingly, several biological pathways related to immune defenses were found to be significantly expanded. Also, more than 40% of the enriched pathways on the positively selected genes (PSGs) were identified to be closely related to immunity and survival. These enriched gene families were inferred to be essential for the P. larvata for defense against the pathogens. However, we did not find a direct genomic basis for its adaptation to omnivorous diet despite multiple attempts of comparative genomic analysis. In addition, we evaluated the susceptibility of the P. larvata to the SARS-CoV-2 by screening the RNA expression of the ACE2 and TMPRSS2/TMPRSS4 genes in 16 organs. Finally, we explored the genome-wide heterozygosity and compared it with other animals to evaluate the population status of this species. Taken together, this chromosome-scale genome of the P. larvata provides a necessary resource and insights for understanding the genetic basis of its biological characteristics, evolution, and disease transmission control.

Nanozyme-Based Bandage with Single-Atom Catalysis for Brain Trauma.

Neurotrauma is one of the most serious traumatic injuries, which can induce an excess amount of reactive oxygen and nitrogen species (RONS) around the wound, triggering a series of biochemical responses and neuroinflammation. Traditional antioxidant-based bandages can effectively decrease infection via preventing oxidative stress, but its effectiveness is limited to a short period of time due to the rapid loss of electron-donating ability. Herein, we developed a nanozyme-based bandage using single-atom Pt/CeO2 with a persistent catalytic activity for noninvasive treatment of neurotrauma. Single-atom Pt induced the lattice expansion and preferred distribution on (111) facets of CeO2, enormously increasing the endogenous catalytic activity. Pt/CeO2 showed a 2-10 times higher scavenging activity against RONS as well as 3-10 times higher multienzyme activities compared to CeO2 clusters. The single-atom Pt/CeO2 retained the long-lasting catalytic activity for up to a month without obvious decay due to enhanced electron donation through the Mars-van Krevelen reaction. In vivo studies disclosed that the nanozyme-based bandage at the single-atom level can significantly improve the wound healing of neurotrauma and reduce neuroinflammation.

Jianpi Jiedu decoction, a traditional Chinese medicine formula, inhibits tumorigenesis, metastasis, and angiogenesis through the mTOR/HIF-1α/VEGF pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine has been utilized for the treatment of cancer. Jianpi Jiedu decoction (JPJD), a traditional Chinese medicine formula, has been used for the treatment of colorectal cancer for decades. However, the underlying molecular mechanistic basis for the effect of JPJD on colorectal cancer is poorly understood. AIM OF THE STUDY: The aim of this study was to identify the effects of JPJD on human colon cancer cells in vitro as well as in vivo and to investigate the mechanistic basis for the anticancer effect of JPJD. MATERIALS AND METHODS: The in vitro antitumor activity of JPJD was assessed by MTT assay, flow cytometric analysis, wound-healing assay, transwell assays, and tube formation assays in order to assess cell activity, apoptosis, migration, invasion, and angiogenesis, respectively. The anticancer properties of JPJD in vivo were assessed by immunohistochemistry in a nude mouse xenograft model of HCT116 cells. In addition, the level of mTOR/HIF-1α/VEGF signaling pathway proteins in HCT116 cells and tumor tissue was evaluated by immunoblotting. RESULTS: In vitro, JPJD significantly inhibited colorectal cancer cell lines viability and proliferation. Flow cytometry analysis demonstrated JPJD to induce HCT116 cell apoptosis. Additionally, JPJD effectively suppressed tumor cell migration, invasion, and angiogenesis by inhibiting the mTOR/HIF-1α/VEGF signaling pathway. In vivo, JPJD significantly inhibited HCT116 tumor growth in athymic nude mice, decreased the levels of CD34 as well as VEGF, and downregulated the mTOR/HIF-1α/VEGF pathway. CONCLUSIONS: JPJD treatment produced anti-colorectal tumor effects by inhibiting tumorigenesis, metastasis, as well as angiogenesis through the mTOR/HIF-1α/VEGF pathway. Thus, these results provide a strong rationale for the therapeutic use of JPJD in cancer treatment. Further studies are required to investigate the mechanisms underlying anti-CRC effect of JPJD.