Single-atom nanozymes: classification, regulation strategy, and safety concerns.

Nanozymes, nanomaterials possessing enzymatic activity, have been studied extensively by researchers. However, their complex composition, low density of active sites, and inadequate substrate selectivity have hindered the maturation and widespread acceptance of nanozymes. Single-atom nanozymes (SAzymes) with atomically dispersed active sites are leading the field of catalysis due to their exceptional performance. The maximum utilization rate of atoms, low cost, well-defined coordination structure, and active sites are the most prominent advantages of SAzymes that researchers favor. This review systematically categorizes SAzymes based on their support type and describes their specific applications. Additionally, we discuss regulation strategies for SAzyme activity and provide a comprehensive summary of biosafety challenges associated with these enzymes.

The preservable effects of ultrasound-assisted alginate oligosaccharide soaking on cooked crayfish subjected to Freeze-Thaw cycles.

To improve the quality of cooked and frozen crayfish after repeated freeze-thaw cycles, the effects of alginate oligosaccharide (1 %, w/v) with ultrasound-assisted (40 W, 3 min) soaking (AUS) on the physicochemical properties were investigated. The AUS samples improved water-holding capacity with 19.47 % higher than the untreated samples. Low-field nuclear magnetic resonance confirmed that mobile water (T22) in the samples after 5 times of freeze-thaw cycles was reduced by 13.02 % and 29.34 % with AUS and without treatment, correspondingly; and with AUS and without treatment, average size of the ice crystals was around 90.26 µm2 and 113.73 µm2, and average diameter of the ice crystals was 5.83 µm and 8.14 µm, respectively; furthermore, it enhanced the solubility and zeta potential, lowered the surface hydrophobicity, reduced the particle size, and maintained the secondary and tertiary structures of myofibrillar protein (MP) after repeated freeze-thawing. Gel electrophoresis revealed that the AUS treatment mitigated the denaturation of MPs. Scanning electron microscopy revealed that the AUS treatment preserved the structure of the tissue. These findings demonstrated that the AUS treatment could enhance the water retention and physicochemical properties of protein within aquatic meat products during temperature fluctuations..

A cascade of transcriptional repression determines sexual commitment and development in Plasmodium falciparum.

Gametocytogenesis, the process by which malaria parasites produce sexual forms that can infect mosquitoes, is essential for the transmission of malaria. A transcriptional switch of the pfap2-g gene triggers sexual commitment, but how the complex multi-step process is precisely programed remains largely unknown. Here, by systematic functional screening of a panel of ApiAP2 transcription factors, we identify six new ApiAP2 members associated with gametocytogenesis in Plasmodium falciparum. Among these, PfAP2-G5 (PF3D7_1139300) was found to be indispensable for gametocytogenesis. This factor suppresses the transcriptional activity of the pfap2-g gene via binding to both the upstream region and exonic gene body, the latter is linked to the maintenance of local heterochromatin structure, thereby preventing initiation of sexual commitment. Removal of this repressive effect through pfap2-g5 knockout disrupts the asexual replication cycle and promotes sexual commitment accompanied by upregulation of pfap2-g expression. However, the gametocytes produced fail to mature fully. Further analyses show that PfAP2-G5 is essential for gametocyte maturation, and causes the down-regulation of pfap2-g and a set of early gametocyte genes activated by PfAP2-G prior to gametocyte development. Collectively, our findings reveal a regulation cascade of gametocyte production in malaria parasites, and provide a new target for transmission blocking interventions.

A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1.

Although artemisinin combination therapies have succeeded in reducing the global burden of malaria, multidrug resistance of the deadliest malaria parasite, Plasmodium falciparum, is emerging worldwide. Innovative antimalarial drugs that kill all life-cycle stages of malaria parasites are urgently needed. Here, we report the discovery of the compound JX21108 with broad antiplasmodial activity against multiple life-cycle stages of malaria parasites. JX21108 was developed from chemical optimization of quisinostat, a histone deacetylase inhibitor. We identified P. falciparum histone deacetylase 1 (PfHDAC1), an epigenetic regulator essential for parasite growth and invasion, as a molecular target of JX21108. PfHDAC1 knockdown leads to the downregulation of essential parasite genes, which is highly consistent with the transcriptomic changes induced by JX21108 treatment. Collectively, our data support that PfHDAC1 is a potential drug target for overcoming multidrug resistance and that JX21108 treats malaria and blocks parasite transmission simultaneously.

The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum.

The tight gene expression regulation controls the development and pathogenesis of human malaria parasite Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in the dynamic gene expression. However, the landscape and related biological functions of nascent non-coding RNAs (ns-ncRNAs) are still poorly explored. Here we profiled the transcription dynamics of nascent RNAs by rRNA-depleted and stranded RNA sequencing over the course of 48-h intraerythrocytic developmental cycle (IDC). We identified the genome-wide sources of a total of 2252 ns-ncRNAs, mostly originating from intergenic and untranslated regions of annotated genes. By integrating the nascent RNA abundances with ATAC-seq and ChIP-seq analysis, we uncovered the euchromatic microenvironment surrounding the ns-ncRNA loci, and revealed a positive correlation between ns-ncRNAs and corresponding mRNA abundances. Finally, by gene knock-down strategy, we showed that the cooperation of RNA exosome catalytic subunit PfDis3 and PfMtr4 cofactor played a major role in ns-ncRNAs degradation. Collectively, this study contributes to understanding of the potential roles of short-lived nascent ncRNAs in regulating gene expression in malaria parasites.

Inhibition of human tumor xenograft growth in nude mice by a conjugate of monoclonal antibody LA22 to epidermal growth factor receptor with anti-tumor antibiotics mitomycin C.

Anti-EGFR monoclonal antibodies LA22 and Erbitux bind to different epitopes of EGFR. The chemimmunoconjugates of MMC with LA22 or Erbitux were prepared, and in vitro cytotoxicity assays with A549 cells showed that LA22-MMC was much more potent than Erbitux or Erbitux-MMC. Viabilities of A549 cells treated with LA22-MMC, Erbitux or Erbitux-MMC were 35%, 94%, and 81%, respectively. Immunoscintigraphy of xenografts of human A431 and A549 cells in nude mice both showed that (125)I-labeled-LA22-MMC enriched in tumor sites prominently. Most importantly, in vivo assays showed LA22-MMC was significantly more effective than free drug MMC in the treatment of subcutaneous xenografts of human A431 cells in nude mice (83% inhibition for LA22-MMC and 30% for MMC). We concluded that LA22-MMC could be a very potent drug for treatment of solid tumors.

[Study on association of interleukin-1 receptor antagonist(RA) gene + 2018 locus mutation with silicosis].

OBJECTIVE: To approach whether + 2018 locus (T-- C) mutation within the interleukin- receptor antagonist (IL-1RA) gene promoter region are associated with susceptibility to silicosis in Southwest Chinese Han population. METHODS: 75 cases of silicosis and 137 silica-exposed workers(being employed) were selected as subjects.5ml peripheral vein blood was drawn from each subject. By real-time quantitative polymerase chain reaction and sequencing techniques, IL-1RA gene mutation of all subjects were analyzed. RESULTS: The frequency of IL-1RA + 2018C among the cases with silicosis was higher than that among the silica-exposed workers (controls) (28.0% versus 15.0% , Fisher' s exact P < 0.01 ). The frequency of allelic C was higher in cases with phase I silicosis than in controls(31.8% versus 15.0%, Fisher's exact P < 0.01 ). The frequency of allelic C was higher in cases with phase I and Ill silicosis than in controls, but which statistic difference being not significant(22.6% versus 15.0%, Fisher's exact P < 0.01). After adjusted for confounding factors, the frequency of IL-1RA + 2018C among silicoses and its subgroups was still higher than among controls, which statistic difference being significant (Fisher' s exact P < 0.01). CONCLUSION: IL-1RA gene polymorphisms played an important role in making the Han population of Southwest China susceptible to silicosis. IL-1RA might be took as a gene to be selected for studying the susceptibility of silicosis.

[On the association of tumor necrosis factor-alpha gene polymorphisms with the susceptibility to silicosis].

OBJECTIVE: To find out whether -308 and -238 locus (G --> A) mutation within the tumor necrosis factor-alpha gene (TNF-alpha) promoter region are associated with susceptibility to silicosis in the Han population of southwest China. METHODS: Governed by the principles of voluntatiness and cooperation, 75 patients with silicosis and 137 control with silica-exposure but without silicosis were recruited, and additionally, 140 elderly patients with silicosis and 135 healthy elderly (retired) controls were recruited in this case-control study. 5 ml peripheral vein blood was drawn from each subject. By means of polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) and sequencing techniques, TNF-alpha gene polymorphisms of all subjects were analyzed. RESULTS: The frequencies of TNF-alpha -308A and -238A in the 75 patients with silicosis were higher than those in the 137 controls (P < 0.01). After being adjusted for confounding factors, the -308A and the -238A were still associated with the presence of silicosis (P < 0.01). But the frequency of TNF-alpha -308A in the 140 elderly patients was significantly lower than that in the controls (P < 0.001). CONCLUSIONS: TNF-alpha gene -308 and -238 locus (G --> A) mutation might be related to the occurrence of silicosis and the severity of pulmonary fibrosis in silicosis among the Han population of southwest China, and TNF2 (-308A) allele might increase the risk of the disease.