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Abstract Background N‐acetyltransferase 10 (NAT10) serves as a critical enzyme in mediating the N4‐acetylcytidine (ac4C) that ensures RNA stability and effective translation processes. The role of NAT10 in driving the advancement of breast cancer remains uninvestigated. Methods We observed an increase in NAT10 expression, both at mRNA level through the analysis of the Cancer Genome Atlas (TCGA) database and at the protein level of tumor tissues from breast cancer patients. We determined that a heightened expression of NAT10 served as a predictor of an unfavorable clinical outcome. By screening the Cancer Cell Line Encyclopedia (CCLE) cell bank, this expression pattern of NAT10 was consistency found across almost all the classic breast cancer cell lines. Results Functionally, interference of NAT10 expression exerts an inhibitory effect on proliferation and invasion of breast cancer cells. By using ac4C RNA immunoprecipitation (ac4c‐RIP) and acRIP‐qPCR assays, we identified a reduction of ac4C enrichment within the ATP binding cassette (ABC) transporters, multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP), consequent to NAT10 suppression. Expressions of MDR1 and BCRP exhibited a positive correlation with NAT10 expression in tumor tissues, and the inhibition of NAT10 in breast cancer cells resulted in a decrease of MDR1 and BCRP expression. Therefore, the overexpressing of MDR1 and BCRP could partially rescue the adverse consequences of NAT10 depletion. In addition, we found that, remodelin, a NAT10 inhibitor, reinstated the susceptibility of capecitabine‐resistant breast cancer cells to the chemotherapy, both in vitro and in vivo. Conclusion The results of our study demonstrated the essential role of NAT10‐mediated ac4c‐modification in breast cancer progression and provide a novel strategy for overcoming chemoresistance challenges.

Abstract Objective To analyse the relationship between the polymorphisms of the H-type hypertensive methylenetetrahydrofolate reductase (MTHFR) C677T gene and neutrophil gelatinase-associated lipocalin (NGAL) in early kidney injury. Method A total of 279 hospitalised patients with hypertension were selected and grouped according to their homocysteine (Hcy) level. If their blood Hcy level was ≥ 10 µmol/L they were assigned to the H-type hypertensive group, and if it was

Caffeic acid (CA) is a phenolic acid compound widely used in pharmaceutical and food applications. However, the efficient synthesis of CA is usually limited by the resources of individual microbial platforms. Here, a cross-kingdom microbial consortium was developed to synthesize CA from sugarcane bagasse hydrolysate using Escherichia coli and Candida glycerinogenes as chassis. In the upstream E. coli module, shikimate accumulation was improved by intensifying the shikimate synthesis pathway and blocking shikimate metabolism to provide precursors for the downstream CA synthesis module. In the downstream C. glycerinogenes module, conversion of p-coumaric acid to CA was improved by increasing the supply of the cytoplasmic cofactor FAD(H2). Further, overexpression of ABC transporter-related genes promoted efflux of CA and enhanced strain resistance to CA, significantly increasing CA titer from 103.8 mg/L to 346.5 mg/L. Subsequently, optimization of the inoculation ratio of strains SA-Ec4 and CA-Cg27 in this cross-kingdom microbial consortium resulted in an increase in CA titer to 871.9 mg/L, which was 151.6% higher compared to the monoculture strain CA-Cg27. Ultimately, 2311.6 and 1943.2 mg/L of CA were obtained by optimization of the co-culture system in a 5 L bioreactor using mixed sugar and sugarcane bagasse hydrolysate, respectively, with 17.2-fold and 14.6-fold enhancement compared to the starting strain. The cross-kingdom microbial consortium developed in this study provides a reference for the production of other aromatic compounds from inexpensive raw materials.

BackgroundNeonatal-onset multisystem inflammatory disease (NOMID) is a rare and severe autoinflammatory disease caused by mutations of the NLRP3 gene and is characterized by a skin rash, fever, arthropathy, and neurologic manifestations. We herein report a neonatal case with recurrent rash, fever, and meningitis from 12 h after birth, and NOMID was diagnosed during the neonatal period. We also reviewed the clinical characteristics and genetic mutations of previously reported Chinese neonates with NOMID.Case presentation and literature reviewNOMID is rare in China, and there have been over 100 cases uncovered thus far, including ours. The patient we reported here was the youngest among the confirmed Chinese cases and had the de novo mutation c.1210G>C (p.V404L) in exon 4 of the NLRP3 gene, which has not been reported previously. All 25 patients manifested recurrent urticaria-like rash, and 24 were febrile. Of the 23 patients with genetic data available, all had NLRP3 mutations. The primary treatment of these patients entailed glucocorticoids and immunosuppressants; however, the IL-1 inhibitor was rarely used due to its current unavailability in China. One patient was cured by umbilical cord blood stem cell transplantation (UCBT), which provided an alternative treatment.ConclusionWe recommend that NOMID be considered for neonates with recurrent rash, fever, and aseptic meningitis. However, further research on underlying mechanisms and therapeutic regimens in China is necessary to provide improved management.

The relative sunspot number is one of the major parameters for the study of long-term solar activity. The automatic calculation of the relative sunspot number is more stable and accurate as compared to manual methods. In this paper, we propose an algorithm that can detect sunspots, and divide them into groups to automatically calculate the relative sunspot number. Mathematical morphology was adopted to detect sunspots then group them. The data set used were the continuum images from SDO/HMI. The process was carried out on the overall HMI data available on the timespan from 2022 January to 2023 May with a time cadence of one day. The experimental results indicated that the method achieved high accuracy of 85.3%. It was well fitted with the international relative sunspot number provided by Solar Influences Data Analysis Center (CC = 0.91). We calculated the conversion factor K value of SDO/HMI for calculating the relative sunspots number ( K = 1.03).

Background Hemorrhagic transformation (HT) is a common complication after intravenous thrombolysis in acute ischemic stroke (AIS), but biomarkers for predicting HT are currently lacking. There is a certain correlation between stress hyperglycemia ratio (SHR) and HT of AIS, but whether SHR is related to the hemorrhagic transformation after intravenous thrombolysis is not very clear. Objective To investigate the relationship between SHR and HT after intravenous thrombolysis in patients with AIS. Methods A total of 320 patients who received recombinant tissue plasminogen activator thrombolytic therapy in Ningbo Medical Center Lihuili Hospital from January 2018 to June 2021 were selected. The clinical data was collected and the value of SHR was calculated. The patients were divided into hemorrhagic transformation group (n=58) and non-hemorrhagic transformation group (n=262) according to the CT/MRI results during the acute period. The demographic data, past medical history, laboratory examination and other clinical data were compared between HT group and non-HT group. Multivariate Logistic regression analysis was used to explore the influencing factors of hemorrhagic transformation in patients with AIS after intravenous thrombolysis; according to the third quartile of SHR, the patients were divided into low SHR group (n=236) and high SHR group (n=84), and the incidence of hemorrhagic transformation was compared between the two groups; according to whether AIS patients had diabetes, the patients were divided into diabetes group (n=79) and non-diabetic group (n=241), and then according to the third quartile of SHR, the groups were divided into low SHR subgroup and high SHR subgroup to explore the influence of diabetes on the relationship between SHR and hemorrhagic transformation. Results Age, baseline National Institutes of Health Stroke Scale (NIHSS) score, percentage of atrial fibrillation, and SHR in the hemorrhagic transformation group were higher than those in the non-hemorrhagic transformation group (P