Emerging roles of RNA ac4C modification and NAT10 in mammalian development and human diseases.

RNA ac4C modification is a novel and rare chemical modification observed in mRNA. Traditional biochemical studies had primarily associated ac4C modification with tRNA and rRNA until in 2018, Arango D et al. first reported the presence of ac4C modification on mRNA and demonstrated its critical role in mRNA stability and translation regulation. Furthermore, they established that the ac4C modification on mRNA is mediated by the classical N-acetyltransferase NAT10. Subsequent studies have underscored the essential implications of NAT10 and mRNA ac4C modification across both physiological and pathological regulatory processes. In this review, we aimed to explore the discovery history of RNA ac4C modification, its detection methods, and its regulatory mechanisms in disease and physiological development. We offer a forward-looking examination and discourse concerning the employment of RNA ac4C modification as a prospective therapeutic strategy across diverse diseases. Furthermore, we comprehensively summarize the functions and mechanisms of NAT10 in gene expression regulation and pathogenesis independent of RNA ac4C modification.

The complete plastome sequence of Artocarpus altilis (Parkinson ex F.A. Zorn) Fosberg, (Moraceae).

Artocarpus altilis (Parkinson ex F.A. Zorn) Fosberg is native to the Pacific Islands, India, and the Philippines. It is also cultivated in Taiwan and Hainan. The complete plastome of the species was assembled and annotated in this study. The circular genome was 160,184 bp in size, presenting a typical quadripartite structure including two inverted repeats (IRs) of 25,734 bp, a large single-copy (LSC) of 88,791 bp, and a small single-copy (SSC) of 19,925 bp. The genome contained 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The total G/C content of complete plastome was 36.0%, with the corresponding values of the LSC, SSC, and IR being 33.7%, 28.8%, and 42.7%, respectively. The complete plastome sequence of A. altilis (Parkinson ex F.A. Zorn) Fosberg will make contributions to the conservation genetics of this species as well as to phylogenetic studies of Moraceae.

Construction of Durvalumab/carbon nanotube/PEI/aptamer-siRNA chimera for the immunotherapy of hepatocellular carcinoma.

Immunotherapy is the most promising treatment for hepatocellular carcinoma (HCC). However, the immunosuppressive microenvironment and necrosis limit its therapeutic effectiveness. Carbon nanotubes (CNTs) have good tissue permeability and can penetrate tumor necrosis area. Here we constructed a Durvalumab/CNT/PEI/aptamer-siRNA chimera (chimera/Durmab/CNT) nanoparticles for the immunotherapy of HCC.In vivoandin vitroexperiments showed that aptamer-siRNA chimeras could specifically bind HCC cells and inhibit the triggering receptor expressed on myeloid cells-2 (Trem2) expression, but had no effect on Trem2 expression in normal liver and lung. Transmission electron microscope results showed that the CNT/PEI nanoparticles were 20-30 nm in diameter and 200-350 nm in length. Dense PEI attachment can be observed on CNTs. CNT/PEI nanoparticles could control the sustained release of Durvalumab for 48 h.In vitroexperimental results showed that chimera/Durmab/CNT could increase the proportion of T cells and CD8 + T cells, and then promote the apoptosis of HepG2 cells, and the therapeutic effect was superior to aptamer/Durmab/CNT and Durmab/CNT. We constructed a tumor-bearing mouse model, and the results showed that chimera/Durmab/CNT significantly inhibited the growth of transplanted tumor, and the volume and proliferation was further reduced in the chimera/Durmab/CNT group compared with the aptamer/Durmab/CNT group. T cells and CD8 + T cells infiltration, and HCC cell apoptosis were significantly increased in the chimera/Durmab/CNT group. In conclusion, we constructed a Durvalumab/CNT/PEI/chimera, which can effectively treat HCC by activating anti-tumor immunity.

[Discussion on ultrasonographic characteristics of schistosomal appendicitis lesions].

OBJECTIVE: To discuss the ultrasonographic characteristics of schistosomal appendicitis lesions. METHODS: Among the patients with schistosomal hepatopathy who were discovered by Color Doppler ultrasound in Huzhou Central Hospital from January 2012 to December 2015, 50 cases with clear history of schistosomiasis and treatment were chosen as a schistosomal hepatopathy group, meanwhile, 50 normal people, who came from non-endemic areas, without schistosomal hepatopathy and schistosomiasis history were chosen as a control group. The two groups were examined by ultrasound scan of the appendix, and the data of the largest diameter of the appendix and the thickness of the appendix wall were collected, and the sonographic characteristics of their appendixes, such as whether the echo of the appendix wall was even or not, were observed. RESULTS: The minimum internal diameter of the appendix cavity and the thickness of the appendix wall of the schistosomal hepatopathy group were (2.090 ± 0.790) mm and (1.332 ± 0.313) mm, respectively, the former was significantly narrower than that of the control group, while the latter was significantly thicker than that of the control group (t = 2.647, - 4.526, respectively, both P＜0.05). The proportions of those with inhomogeneous echo, indistinctness structure, uneven thickening of the appendix wall, as well as having intestinal contents in the appendix cavity in the schistosomal hepatopathy group were higher than those in the control group (χ2 = 12.000, 18.537, 24.008, 4.244, respectively, all P＜0.05). CONCLUSIONS: Schistosomal appendicitis lesions have obvious ultrasonographic characteristics under ultrasound. Ultrasound can play an important role in judging whether the appendix of schistosomiasis patients is involved and discovering the lesion of appendix early.

A Dual-Response Fluorescent Probe Reveals the H2 O2 -Induced H2 S Biogenesis through a Cystathionine ß-Synthase Pathway.

The two signaling molecules H2 S and H2 O2 play key roles in maintaining intracellular redox homeostasis. The biological relationship between H2 O2 and H2 S remains largely unknown in redox biology. In this study, we rationally designed and synthesized single- and dual-response fluorescent probes for detecting both H2 O2 and H2 S in living cells. The dual-response probe was shown to be capable of mono- and dual-detection of H2 O2 and H2 S selectively and sensitively. Detailed bioimaging studies based on the probes revealed that both exogenous and endogenous H2 O2 could induce H2 S biogenesis in living cells. By using gene-knockdown techniques with bioimaging, the H2 S biogenesis was found to be majorly cystathionine ß-synthase (CBS)-dependent. Our finding shows the first direct evidence on the biological communication between H2 O2 (ROS) and H2 S (RSS) in vivo.

A highly selective and fast-response fluorescent probe for visualization of enzymatic H2S production in vitro and in living cells.

An o-fluorinated-azido-capped rhodamine probe can react with H2S efficiently and selectively to give large off-on fluorescence enhancement. The probe was used to develop an assay for cystathionine ß-synthase acitivity and for in situ visualization of endogenously produced H2S in living cells.

A FRET-ICT dual-quenching fluorescent probe with large off-on response for H2S: synthesis, spectra and bioimaging.

A FRET-ICT dual-quenching probe with large off-on fluorescent response upon H2S treatment is reported. The probe can be used for bioimaging of endogenous H2S in living cells.

o-Fluorination of aromatic azides yields improved azido-based fluorescent probes for hydrogen sulfide: synthesis, spectra, and bioimaging.

Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule with multiple biological functions. To visualize the endogenous in situ production of H2S in real time, new coumarin- and boron-dipyrromethene-based fluorescent turn-on probes were developed for fast sensing of H2S in aqueous buffer and in living cells. Introduction of a fluoro group in the ortho position of the aromatic azide can lead to a greater than twofold increase in the rate of reaction with H2S. On the basis of o-fluorinated aromatic azides, fluorescent probes with high sensitivity and selectivity toward H2S over other biologically relevant species were designed and synthesized. The probes can be used to in situ to visualize exogenous H2S and D-cysteine-dependent endogenously produced H2S in living cells, which makes them promising tools for potential applications in H2S biology.

[Advance in studies on anti-inflammatory and immunoregulatory monomers of Tripterygium wilfordii].

Tripterygium wilfordii has complex chemical components. To study and summarize the advance in studies on the anti-inflammatory and immunoregulatory activities and toxicology of known monomers of T. wilfordii, the pertinent literatures related to the studies on the pharmacology, toxicology and pharmacokinetics of T. wilfordii over past 30 years were searched. According to the findings, more than ten anti-inflammatory and immunoregulatory monomers were found in T. wilfordii. The pharmacology and toxicology of wilforidine, triptolidenol, triptonide, demethylzeylasteral shall be further studied.

Posterior rotating rod reduction strategy for irreducible atlantoaxial subluxations with congenital odontoid aplasia.

STUDY DESIGN: Applying rotating rod techniques to reduce irreducible atlantoaxial dislocation. OBJECTIVE: To spare the occipital-C1 motion by the strategy in reduction of before surgery irreducible atlantoaxial dislocation with obvious neurologic symptoms and congenital odontoid aplasia. SUMMARY OF BACKGROUND DATA: The treatment of atlantoaxial dislocation (AAD) is a challenging problem for most surgeons. Posterior surgical stabilization of C1 and C2 include C1-C2 transarticular screws, or C1 lateral with C2 pars screws. These constructs, however, are based on preoperative reductions. When preoperative skull reduction fails and myelopathic symptoms coexist, long-segment cervico-occipital fusion and decompression are usually the only practical choice. METHODS: The authors explored a different surgical technique to spare the axial occipital joints by rotating rods in polyaxial C1, C3 lateral mass, and C2 pars screws, functioning as a lever analogue. Three before surgery irreducible AAD cases with obvious neurologic symptoms and congenital odontoid aplasia were successfully reduced and fused with this procedure. The authors used intraoperative somatosensory-evoked potential monitoring and intraoperative fluoroscopy. Preoperative skull traction was employed to distract and help extend the atlantoaxial complexes. RESULTS: Three C1-C2 dislocations were reduced completely without any deterioration of neurologic signs. Cervical myelopathic symptoms recovered soon after the operation. No atlantoaxial subluxation recurred. They returned to their normal work and/or activities. CONCLUSION: The rotating rod strategy is a viable option to reduce and fuse C1-C3 for AAD with odontoid aplasia. It spares the occipital-C1 motion.

Impact of hepatitis C virus coinfection on HAART in HIV-infected individuals: multicentric observation cohort.

OBJECTIVE: To evaluate the influence of hepatitis C virus (HCV) coinfection on clinical, immunological, and virological responses and on adverse reactions to nevirapine-containing highly active antiretroviral therapy (HAART) in Chinese adult antiretroviral-naive HIV-positive patients. METHODS: This prospective, multicentric study enrolled 175 HIV-1-positive subjects who initiated HAART and attended follow-up visits over 100 weeks from 2005 to 2007. They were grouped based on HCV antibody and HCV RNA test results. Virological and immunological responses and adverse events were monitored at baseline and at the end of weeks 4, 12, 24, 36, 52, 68, 84, and 100. For data analyses, we used repeated measures of variance. RESULTS: There were 117 patients who were HCV antibody negative (anti-HCV-), 24 who were anti-HCV+ but HCV RNA-, and 34 who were anti-HCV+ and HCV RNA+. Compared with both anti-HCV- group and anti-HCV+ HCV RNA- group, the anti-HCV+ HCV RNA+ group had a higher incidence of rash (P = 0.044) and hepatotoxicity (P = 0.001) from adverse drug reactions. We observed no statistically significant differences in viral load responses among the 3 groups during follow-up. CD4 and CD8 T-cell responses were similar among the 3 groups. CONCLUSIONS: HCV/HIV coinfection does not affect immunological and virological responses to HAART. However, the positive anti-HCV and HCV RNA in serum worsened adverse drug reactions to HAART such as rash and hepatoxicity in HIV patients.