METTL14 modulates glycolysis to inhibit colorectal tumorigenesis in p53-wild-type cells.

The frequency of p53 mutations in colorectal cancer (CRC) is approximately 40-50%. A variety of therapies are being developed to target tumors expressing mutant p53. However, potential therapeutic targets for CRC expressing wild-type p53 are rare. In this study, we show that METTL14 is transcriptionally activated by wild-type p53 and suppresses tumor growth only in p53-wild-type (p53-WT) CRC cells. METTL14 deletion promotes both AOM/DSS and AOM-induced CRC growth in mouse models with the intestinal epithelial cell-specific knockout of METTL14. Additionally, METTL14 restrains aerobic glycolysis in p53-WT CRC, by repressing SLC2A3 and PGAM1 expression via selectively promoting m6 A-YTHDF2-dependent pri-miR-6769b/pri-miR-499a processing. Biosynthetic mature miR-6769b-3p and miR-499a-3p decrease SLC2A3 and PGAM1 levels, respectively, and suppress malignant phenotypes. Clinically, METTL14 only acts as a beneficial prognosis factor for the overall survival of p53-WT CRC patients. These results uncover a new mechanism for METTL14 inactivation in tumors and, most importantly, reveal that the activation of METTL14 is a critical mechanism for p53-dependent cancer growth inhibition, which could be targeted for therapy in p53-WT CRC.

Detection of Doxycycline Using Carbon Quantum dots as Probe Based on Internal Filtering Effect.

The establishment of a convenient and effective detection method for doxycycline (DC) holds significant importance in drug monitoring and drug residue assessment. In this work, carbon quantum dots (CQDs) with excellent and stable luminescence performance (the quantum yield of CQDs was 21.8%) were synthesized by the melting method and employed as probes to monitor the fluorescence intensity variations before and after the introduction of DC. A fluorescence analytical method based on the internal filtration effect (IFE) was developed for DC determination. The mechanism of DC quenching CQDs was verified using fluorescence lifetime tests, absorption spectroscopy, and evaluation of internal filtration parameters. After optimizing experimental conditions, it was found that the DC concentration (CDC) exhibited a good linear relationship with the fluorescence quenching efficiency ((F0-F)/F0) of CQDs in the range of 5-30 µM. The fitted linear equation was Y = 0.01249*CDC+0.03625, R2 = 0.9987, and the detection limit was 2.343 µM (n = 8). This developed method has been successfully applied to accurately determine DC concentrations in both doxycycline hydrochloride tablets and human serum samples. It stands out for its simplicity, rapidity, and acceptable detection performance. Due to its advantages, this method holds great promise for application in the biomedical field for monitoring DC drug concentrations and ensuring quality control.

Induction of a Long Noncoding RNA Transcript, NR_045064, Promotes Defense Gene Transcription and Facilitates Intestinal Epithelial Cell Responses against Cryptosporidium Infection.

Cryptosporidium is an important opportunistic intestinal pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Gastrointestinal epithelial cells play a central role in activating and orchestrating host immune responses against Cryptosporidium infection, but underlying molecular mechanisms are not fully understood. We report in this paper that C. parvum infection causes significant alterations in long noncoding RNA (lncRNA) expression profiles in murine intestinal epithelial cells. Transcription of a panel of lncRNA genes, including NR_045064, in infected cells is controlled by the NF-κB signaling. Functionally, inhibition of NR_045064 induction increases parasite burden in intestinal epithelial cells. Induction of NR_045064 enhances the transcription of selected defense genes in host cells following C. parvum infection. Epigenetic histone modifications are involved in NR_045064-mediated transcription of associated defense genes in infected host cells. Moreover, the p300/MLL-associated chromatin remodeling is involved in NR_045064-mediated transcription of associated defense genes in intestinal epithelial cells following C. parvum infection. Expression of NR_045064 and associated genes is also identified in intestinal epithelium in C57BL/6J mice following phosphorothioate oligodeoxynucleotide or LPS stimulation. Our data demonstrate that lncRNAs, such as NR_045064, play a role in regulating epithelial defense against microbial infection.

Artemyrianolides A-S, Cytotoxic Sesquiterpenoids from Artemisia myriantha.

Random screening suggested that the EtOH extract of Artemisia myriantha (Asteraceae) and its EtOAc fraction had cytotoxicity against HepG2 cells with inhibitory ratios of 30.6% and 53.5% at 50.0 µg/mL. Bioassay-guided isolation of the most active fractions (Fr. C and Fr. D) afforded 19 new sesquiterpenolides, artemyrianolides A-S (1-19), involving 13 germacranolides (1-13), four guaianolides (14-17), and two eudesmanolides (18 and 19), together with 16 known sesquiterpenoids (20-35). The new compounds were characterized by physical data analyses (HRESIMS, IR, 1D and 2D NMR, ECD), and the absolute configurations of compounds 1, 2, and 11 were determined by X-ray crystallography. Structurally, compounds 2 and 11-13 maintain an uncommon cis-fused 10/5 bicyclic system and compound 12 possesses an unusual (7S) configuration. Twenty of the compounds exhibited cytotoxicity against HepG2, Huh7, and SMMC-7721 cell lines. Compound 9 showed cytotoxic activity on both HepG2 and Huh7 cells with IC50 values of 8.6 and 8.8 µM, and compounds 8 and 33 showed cytotoxicity to the three human hepatoma cell lines with IC50 values of 4.9 and 7.4 µM (HepG2), 4.3 and 7.8 µM (Huh7), and 3.1 and 9.8 µM (SMMC-7721), respectively.

Variations in chromosomal aneuploidy rates in IVF blastocysts and early spontaneous abortion chorionic villi.

PURPOSE: To compare chromosomal aberrations and aneuploidy features in (i) blastocysts following intracytoplasmic sperm injection (ICSI) and trophectoderm (TE) biopsy using preimplantation genetic screening (PGS) and (ii) early spontaneous abortion chorionic villus biopsies (SA-CVB) using single-nucleotide polymorphism (SNP) array detection. METHODS: We retrospectively reviewed the data for 1014 TEs from 220 PGS cycles and 1724 SA-CVBs originating from naturally pregnant couples and patients undergoing assisted reproductive technology (ART) during 2017 to 2018. SNP array was applied in both PGS and SA-CVBs detection. Aberrations were defined, and the frequency and ratio of each chromosome aberration were compared between the two groups. RESULTS: There were more abnormalities in TEs in the form of complex chromosome aneuploidies and monosomies, while SA-CVBs had more trisomies, sex chromosome abnormalities, and polyploidies. In both groups, chromosomal aneuploidies (including monosomies and trisomies) were confined to chromosomes 14, 15, 16, 18, 21, and 22, but showed varying distributions across the groups. Aneuploidy of chromosome 22 was most frequent in TEs, whereas that of chromosome 16 predominated in SA-CVBs. Among the sex chromosome abnormalities, X monosomies were significantly more prevalent in SA-CVBs. CONCLUSIONS: Chromosomal aberrations and aneuploidy manifested specific characteristics that differed between TEs and SA-CVBs, which indicates that distinct chromosomal abnormalities can affect certain developmental stages of embryos. Further analysis is needed to explore the chromosomal mechanisms affecting embryo development and implantation. Such information will help clinical assessments in prenatal diagnosis and reduce the incidence of genetically abnormal fetuses.

Induction of Inflammatory Responses in Splenocytes by Exosomes Released from Intestinal Epithelial Cells following Cryptosporidium parvum Infection.

Cryptosporidium, a protozoan parasite that infects the gastrointestinal epithelium and other mucosal surfaces in humans and animals, is an important opportunistic pathogen in AIDS patients and one of the most common enteric pathogens affecting young children in developing regions. This parasite is referred to as a "minimally invasive" mucosal pathogen, and epithelial cells play a central role in activating and orchestrating host immune responses. We previously demonstrated that Cryptosporidium parvum infection stimulates host epithelial cells to release exosomes, and these released exosomes shuttle several antimicrobial peptides to carry out anti-C. parvum activity. In this study, we detected the upregulation of inflammatory genes in the liver and spleen following C. parvum intestinal infection in neonatal mice. Interestingly, exosomes released from intestinal epithelial cells following C. parvum infection could activate the nuclear factor kappa B signaling pathway and trigger inflammatory gene transcription in isolated primary splenocytes. Several epithelial cell-derived proteins and a subset of parasite RNAs were detected in the exosomes released from C. parvum-infected intestinal epithelial cells. Shuttling of these effector molecules, including the high mobility group box 1 protein, was involved in the induction of inflammatory responses in splenocytes induced by the exosomes released from infected cells. Our data indicate that exosomes released from intestinal epithelial cells upon C. parvum infection can activate immune cells by shuttling various effector molecules, a process that may be relevant to host systemic responses to Cryptosporidium infection.

EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/ß-catenin pathway.

Epidermal growth factor-like protein 6 (EGFL6) serves as an exocrine protein promoting proliferation and migration during carcinogenesis in ovarian cancer. However, its function and mechanisms in colorectal cancer (CRC) have not been completely explored. To investigate the role of EGFL6 in CRC cell growth, in vitro CCK8, colony formation assays, flow cytometric analysis of the cell cycle and apoptosis, and an in vivo tumor xenograft model were utilized. Additionally, Western blotting and luciferase reporter assays were used to investigate the underlying mechanisms of EGFL6 function on the WNT/ß-catenin signaling pathway. Immunohistochemical staining showed that EGFL6 is overexpressed in CRCs and this overexpression was highly correlated with advanced T classification, N classification, distant metastasis, and poor survival. Knocking down EGFL6 in CRC cell lines induced the inhibition of cell growth, cell cycle arrest at the G0/G1 phase, and apoptosis. Further, knockdown of EGFL6 blocked WNT/ß-catenin signaling as measured by Western blotting and luciferase reporter assay. Results also showed that recombinant EGFL6 (rEGFL6) induced ß-catenin in a concentration- and time-dependent manner. Further experiments showed that administration of rEGFL6 to cell cultures with EGFL6 knocked down or treated with the WNT/ß-catenin inhibitor ICG-001 increased ß-catenin and its downstream protein CyclinD1. The CCK8 assay showed that EGFL6 promoted CRC cell growth partly by the promotion of TCF7L2 expression. These findings suggest that EGFL6 plays a crucial role in the progression of CRC by regulation of the WNT/ß-catenin signaling pathway.

Clinicopathological characteristics and health care for Tibetan women with breast cancer: a cross-sectional survey.

BACKGROUND: The healthcare system (HCS) improved in Tibet Autonomous Region (TAR), China. The present study aimed to investigate whether these improvements might alter the clinicopathological characteristics of a Tibetan female with breast cancer (BC) in TAR. METHODS: This was a single-center cross-sectional study conducted at TAR People's Hospital. All Tibetan adult women were treated for BC in this hospital between January 1, 1973 and December 31, 2015. The inclusion criteria were as follows: (1) Tibetan adult woman living in Tibet; (2) Histopathology or cytopathology or both confirming primary BC; (3) All the treatments were finished in this hospital. χ2 test and logistic regression were applied, using age group and census register as the two covariates. RESULTS: A total of 273 patients with BC were included in the final analysis. Of these, 14 patients were in the free HCS, 183 patients had medical insurance combined with a new rural cooperative HCS, and 76 were in a rural and urban integration HCS. Currently, a rural and urban integration HCS is an improved system. Consequently, an increase in the proportion patients in the T1-3 stage was observed (0.198; 0.046 to 0.852) between the rural and urban integration HCS and free HCS. The proportion of patients in early (I + II) stage cancer (0.110; 0.019-0.633) also increased between these two HCSs. CONCLUSION: This was the first report about Tibetan women with BC in Tibet. Some clinicopathological characteristics at the presentation of Tibetan women with BC may improve during different HCSs. The cancer awareness, early detection, and the overall management in patients with advanced stage BC might improve the prognosis of BC in the rural and urban integration HCS.

Attenuation of Intestinal Epithelial Cell Migration During Cryptosporidium parvum Infection Involves Parasite Cdg7_FLc_1030 RNA-Mediated Induction and Release of Dickkopf-1.

Intestinal infection by Cryptosporidium is known to cause epithelial cell migration disorder but the underlying mechanisms are unclear. Previous studies demonstrated that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected epithelial cells. Using multiple models of intestinal cryptosporidiosis, we report here that C. parvum infection induces expression and release of the dickkopf protein 1 (Dkk1) from intestinal epithelial cells. Delivery of parasite Cdg7_FLc_1030 RNA to intestinal epithelial cells triggers transactivation of host Dkk1 gene during C. parvum infection. Release of Dkk1 is involved in C. parvum-induced inhibition of cell migration of epithelial cells, including noninfected bystander cells. Moreover, Dkk1-mediated suppression of host cell migration during C. parvum infection involves inhibition of Cdc42/Par6 signaling. Our data support the hypothesis that attenuation of intestinal epithelial cell migration during Cryptosporidium infection involves parasite Cdg7_FLc_1030 RNA-mediated induction and release of Dkk1 from infected cells.

Trans-suppression of defense DEFB1 gene in intestinal epithelial cells following Cryptosporidium parvum infection is associated with host delivery of parasite Cdg7_FLc_1000 RNA.

To counteract host immunity, Cryptosporidium parvum has evolved multiple strategies to suppress host antimicrobial defense. One such strategy is to reduce the production of the antimicrobial peptide beta-defensin 1 (DEFB1) by host epithelial cells but the underlying mechanisms remain unclear. Recent studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of intestinal cryptosporidiosis, in this study, we analyzed the expression profile of host beta-defensin genes in host cells following infection. We found that C. parvum infection caused a significant downregulation of the DEFB1 gene. Interestingly, downregulation of DEFB1 gene was associated with host delivery of Cdg7_FLc_1000 RNA transcript, a C. parvum RNA that has previously demonstrated to be delivered into the nuclei of infected host cells. Knockdown of Cdg7_FLc_1000 in host cells could attenuate the trans-suppression of host DEFB1 gene and decreased the parasite burden. Therefore, our data suggest that trans-suppression of DEFB1 gene in intestinal epithelial cells following C. parvum infection involves host delivery of parasite Cdg7_FLc_1000 RNA, a process that may be relevant to the epithelial defense evasion by C. parvum at the early stage of infection.

Involvement of Cryptosporidium parvum Cdg7_FLc_1000 RNA in the Attenuation of Intestinal Epithelial Cell Migration via Trans-Suppression of Host Cell SMPD3.

Intestinal infection by Cryptosporidium parvum causes inhibition of epithelial turnover, but underlying mechanisms are unclear. Previous studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected epithelial cells. Using in vitro and in vivo models of intestinal cryptosporidiosis, we report here that host delivery of parasite Cdg7_FLc_1000 RNA results in inhibition of epithelial cell migration through suppression of the gene encoding sphingomyelinase 3 (SMPD3). Delivery of Cdg7_FLc_1000 into infected cells promotes the histone methyltransferase G9a-mediated H3K9 methylation in the SMPD3 locus. The DNA-binding transcriptional repressor, PR domain zinc finger protein 1, is required for the assembly of Cdg7_FLc_1000 into the G9a complex and associated with the enrichment of H3K9 methylation at the gene locus. Pathologically, nuclear transfer of Cryptosporidium parvum Cdg7_FLc_1000 RNA is involved in the attenuation of intestinal epithelial cell migration via trans-suppression of host cell SMPD3.

LincRNA-Cox2 modulates TNF-α-induced transcription of Il12b gene in intestinal epithelial cells through regulation of Mi-2/NuRD-mediated epigenetic histone modifications.

Long intergenic noncoding RNAs (lincRNAs) can regulate the transcription of inflammatory genes and thus may represent a new group of inflammatory mediators with a potential pathogenic role in inflammatory diseases. Here, our genome-wide transcriptomic data show that TNF-α stimulation caused up-regulation of 171 lincRNAs and down-regulation of 196 lincRNAs in murine intestinal epithelial cells in culture. One of the up-regulated lincRNAs, lincRNA-Cox2, is an early-responsive lincRNA induced by TNF-α through activation of the NF-ĸB signaling pathway. Knockdown of lincRNA-Cox2 resulted in reprogramming of the gene expression profile in intestinal epithelial cells in response to TNF-α stimulation. Specifically, lincRNA-Cox2 silencing significantly (P < 0.05) enhanced the transcription of Il12b, a secondary late-responsive gene induced by TNF-α. Mechanistically, lincRNA-Cox2 promoted the recruitment of the Mi-2/nucleosome remodeling and deacetylase (Mi-2/NuRD) repressor complex to the Il12b promoter region. Recruitment of the Mi-2/NuRD complex was associated with decreased H3K27 acetylation and increased H3K27 dimethylation at the Il12b promoter region, which might contribute to Il12b trans-suppression by lincRNA-Cox2. Thus, our data demonstrate a novel mechanism of epigenetic modulation by lincRNA-Cox2 on Il12b transcription, supporting an important role for lincRNAs in the regulation of intestinal epithelial inflammatory responses.

Narrow-band imaging in the diagnosis of deep submucosal colorectal cancers: a systematic review and meta-analysis.

Background and aims Magnifying endoscopy with narrow-band imaging (M-NBI) has been widely used in the differential diagnosis of deep submucosal colorectal cancers (dSMCs) from superficial submucosal cancers (sSMCs) and intramucosal neoplasms. We aimed to pool the diagnostic efficacy of M-NBI and compare it with that of magnifying chromoendoscopy (M-CE) in diagnosing colorectal dSMC. Methods PubMed, EMBASE, and the Cochrane Library were searched to identify eligible studies. Meeting abstracts were also searched. A bivariate mixed-effects binary regression model was used in the meta-analysis to calculate the pooled diagnostic efficacy of M-NBI and compare it with that of M-CE in the diagnosis of dSMC. Subgroup analyses and meta-regression were conducted to explore sources of heterogeneity. Results We included 17 studies: 14 full texts and 3 meeting abstracts. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) with 95 % confidence intervals (CIs) in diagnosing dSMC were 74 % (66 % - 81 %; I2 = 84.6 %), 98 % (94 % - 99 %; I2 = 94.4 %), and 0.91 (0.88 - 0.93), respectively, for M-NBI. The pooled sensitivity, specificity and AUC (95 %CI) were 84 % (76 % - 89 %; I2 = 76.9 %), 97 % (94 % - 99 %; I2 = 90.2 %), and 0.97 (0.95 - 0.98), respectively, for M-CE. M-NBI had lower sensitivity (P < 0.01) than M-CE with similar specificity (P = 0.32). Subgroup analyses and meta-regression indicated that endoscopic diagnostic criteria, study type, endoscope type, risk of index test bias, and histopathological diagnostic criteria might be the sources of heterogeneity. Conclusions M-NBI and M-CE had comparable specificities in diagnosing dSMC, but the sensitivity of M-NBI was slightly lower than that of M-CE.

Association of peroxisome proliferator-activated receptorγ gene Pro12Ala and C161T polymorphisms with cardiovascular risk factors in maintenance hemodialysis patients.

The Pro12Ala and C161T polymorphisms in peroxisome proliferator-activated receptor γ (PPARγ) have been shown to be associated with carotid artery atherosclerosis. It remains unclear whether these two polymorphisms are associated with risk factors for cardiovascular disease (CVD) in hemodialysis (HD) patients. Therefore, the PPARγ genotypes in 99 HD patients and 149 controls were determined, and clinical characteristics among the different genotypes were compared. We found that the frequency of the Pro12Ala and C161T polymorphisms in HD patients was similar to that in healthy controls, but C161T polymorphism and T allele frequencies in HD patients with CVD were lower than that in HD patients without CVD. Carotid artery plaque (CAP) and carotid intima-media thickness (CIMT) in HD patients with CT + TT or Pro12Ala genotypes were also less than that in patients with CCor Pro12Pro genotypes, respectively. HD patients with CT + TT genotype had lower serum C reactive protein (CRP) levels, as well as higher triceps skin fold (TSF) thickness, mid arm circumference (MAC) and mean mid arm circumference (MMAC) than HD patients with CC genotype (P < 0.05). Moreover, CIMT of the Pro12Ala-CT161 subgroup was less than the Pro12Pro-CC161 and Pro12Pro-CT161 subgroup, and, CAP amounts of the Pro12Ala-CT161 subgroup was less than the Pro12Pro-CC161 subgroup. Our results indicate that the Pro12Ala and C161T polymorphisms were associated with some important risk factors for CVD in HD patients in the Han Chinese population.

Endowing Polyetheretherketone with Anti-Infection and Immunomodulatory Properties through Guanidination Carbon Dots Modification to Promote Osseointegration in Diabetes with MRSA Infection.

Methicillin-resistant Staphylococcus aureus (MRSA) infection and compromised immunity are the severe complications associated with implantation surgery in diabetes mellitus. Enhancing the antibacterial and immunomodulatory properties of implants represents an effective approach to improve the osseointegration of implant in diabetes mellitus. Herein, guanidination carbon dots (GCDs) with antibacterial and immunoregulatory functions are synthesized. The GCDs demonstrate killing effect on MRSA without detectable induced resistance. Additionally, they promote the polarization of macrophages from the M1 to M2 subtype, with the inhibiting pro-inflammatory cytokines and promoting anti-inflammatory factors. Correspondingly, GCDs are immobilized onto sulfonated polyether ether ketone (SP@GCDs) using a polyvinyl butyraldehyde (PVB) coating layer through soaking-drying technique. SP@GCDs maintain stable antibacterial efficacy against MRSA for six consecutive days and retain the immunomodulatory function, while also possessing the long-term storage stability and biocompatibility of more than 6 months. Moreover, SP@GCDs significantly promote the proliferation and mineralization of osteoblasts. SP@GCDs facilitate osteogenesis through immunoregulatory. Additionally, SP@GCDs exert stable antibacterial and immune regulatory functions in implantation site of a diabetes rat, effectively promoting implant osseointegration regardless of the MRSA infection. These findings provide valuable insights into implant modification through designing nanomaterials with multifunction for enhancing osseointegration of diabetes mellitus, suggesting the promising clinical application prospects.

Global research trends and hotspots of PI3K/Akt signaling pathway in the field of osteoarthritis: A bibliometric study.

The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway has gradually become a new target for the treatment of osteoarthritis (OA). Numerous studies of PI3K/Akt signaling in OA have been published in the past few years. By analyzing these research characteristics and qualities, we aimed to reveal the current research focus and emerging trends in PI3K/Akt signaling in OA. We searched the Web of Science database for relevant articles concerning the PI3K/Akt signaling pathway in OA published from inception to October 31, 2022. The following data were extracted: author name, article title, keywords, topic, publication country/region, institution, publication journal, journal impact factor, number of times cited, and H-index. VOSviewer and Excel 2019 were used to conduct the bibliometric study and visualize the analysis. A total of 374 publications were included in this study. In all selected articles, "orthopedics" was the dominant topic (252 of 374, 67.38%). The most productive year was 2021. Frontiers in Pharmacology published the most articles. The People's Republic of China has published the most articles worldwide. The top 5 keywords were "OA," "expression," "apoptosis," "chondrocytes," and "inflammation." The keywords "autophagy," "mitochondrial dysfunction," "inflammatory response," "cartilage degeneration," and "network pharmacology" have increased in recent years. Our study showed a growing trend in published articles related to the PI3K/Akt signaling pathway in OA. Inflammatory response, cartilage degeneration, and apoptosis remain central topics in the field. Research on autophagy, mitochondrial dysfunction, and network pharmacology is on the rise, and the focus on PI3K/Akt will continue to increase.

Quaternized carbon dots with enhanced antimicrobial ability towards Gram-negative bacteria for the treatment of acute peritonitis caused by E. coli.

Infections caused by Gram-negative bacteria still pose a clinical challenge. Although nanomaterials have been developed for antibacterial treatments, a systematic evaluation of the mechanisms and intervention models of antibacterial materials toward Gram-negative bacteria is still lacking. Herein, antibacterial quaternized carbon dots (QCDs) were synthesized via a one-step melting method using anhydrous citric acid and diallyl dimethyl ammonium chloride (DDA). The QCDs exhibited effective broad-spectrum antibacterial activity and enhanced inhibitory ability towards Gram-negative bacteria. The antibacterial mechanism of the QCDs with respect to Gram-negative bacteria was investigated through the characterization of bacterial morphology changes, the absorption modes of the QCDs on bacteria, and the potential generation of reactive oxygen species by the QCDs. The QCDs showed low toxicity in different cells, and did not cause hemolysis. The QCDs were administered via intraperitoneal injection to treat acute peritonitis in mice infected with E. coli. Routine blood examination, magnetic resonance imaging, and pathological analysis were undertaken and it was found that, similar to the positive control group treated with gentamicin sulfate, the QCDs exhibited a therapeutic effect that eliminated infection and inflammation. This study explores a controllable synthetic strategy for the synthesis of active carbon dots with antibacterial activity, a material that is a promising candidate for new treatments of Gram-negative bacterial infections.

Splicing factor SF3B3, a NS5-binding protein, restricts ZIKV infection by targeting GCH1.

Zika virus (ZIKV), a positive-sense single-stranded RNA virus, causes congenital ZIKV syndrome in children and Guillain-Barré Syndrome (GBS) in adults. ZIKV expresses nonstructural protein 5 (NS5), a large protein that is essential for viral replication. ZIKV NS5 confers the ability to evade interferon (IFN) signalling; however, the exact mechanism remains unclear. In this study, we employed affinity pull-down and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses and found that splicing factor 3b subunit 3 (SF3B3) is associated with the NS5-Flag pull-down complex through interaction with NS5. Functional assays showed that SF3B3 overexpression inhibited ZIKV replication by promoting IFN-stimulated gene (ISG) expression whereas silencing of SF3B3 inhibited expression of ISGs to promote ZIKV replication. GTP cyclohydrolase I (GCH1) is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis. NS5 upregulates the expression of GCH1 during ZIKV infection. And GCH1 marginally promoted ZIKV replication via the IFN pathway. Additionally, GCH1 expression is related to the regulation of SF3B3. Overexpression of the SF3B3 protein effectively reduced GCH1 protein levels, whereas SF3B3 knockdown increased its levels. These findings indicated that ZIKV NS5 binding protein SF3B3 contributed to the host immune response against ZIKV replication by modulating the expression of GCH1.