Bacteremia and associated bacterial sepsis are potentially fatal and occur when the host response to microbial invasion is impaired or compromised. This motivated us to develop carbonized polymer ...dots (CPDs
Man/AA
) from a mixture of mannose (Man) and positively charged amino acids AAs; lysine, arginine (Arg), or histidine through a one-step mild pyrolysis procedure, which effectively inhibited drug-resistant bacterial strains isolated from septic patients. The as-prepared CPDs
Man/AA
showed broad-spectrum antibacterial activity, including multidrug-resistant bacteria, even in human plasma. The minimal inhibitory concentration of CPDs
Man/Arg
is
ca.
1.0 μg mL
−1
, which is comparable to or lower than those of other tested antibiotics (
e.g.
, ampicillin, gentamicin, and vancomycin). In addition to directly disrupting bacterial membranes, the CPDs
Man/Arg
feature a structure similar to aminoglycoside antibiotics that could bind to 16S rRNA, thereby blocking bacterial protein synthesis
. In vitro
cytotoxic and hemolytic assays demonstrated the high biocompatibility of the CPDs
Man/AA
. In addition,
in vivo
studies on methicillin-resistant
Staphylococcus aureus
-infected mice treated with the CPDs
Man/Arg
showed a significant decrease in mortality-even better than that of antibiotics. Overall, the synthesis of the CPDs
Man/AA
is cost-efficient, straightforward, and effective for treating bacteremia. The polymeric features of the CPDs
Man/Arg
, including cationic charges and specific groups, can be recognized as a safe and broad-spectrum biocide to lessen our reliance on antibiotics to treat systemic bacterial infections in the future.
Aminoglycoside-mimicking carbonized polymer dots (CPDs) for bacteremia treatment by blocking the synthesis of bacterial proteins and disrupting bacterial membranes.
The catalyst‐controlled diversity‐oriented synthesis of spirohydroquinoline‐indandiones and 3‐methylenehydroquinoline‐indandiones from ortho‐sulfonamidophenyl‐substituted para‐quinone methides and ...allylidene‐indandiones is reported. The strategies utilized an organobase such as DMAP or TMG to control the reaction pathway chemoselectively, furnishing the corresponding products in 40–99% yields with excellent diastereoselectivities. The mechanistic studies revealed that spirohydroquinoline‐indandione was the kinetic product to afford 3‐methylenehydroquinoline‐indandione in the presence of TMG, which probably involved an unusual base‐initiated 1,3‐nitrogen rearrangement process.
Background
Prior studies indicated a link between urinary catheter use and urinary complications, highlighting the need for comprehensive, gender‐specific investigations. This study explored the ...association through a national retrospective cohort, emphasizing gender disparities and long‐term outcomes.
Methods
Our study utilized data from the entire population covered by Taiwan's National Health Insurance Research Database from 2000 to 2017. We included 148,304 patients who had undergone Foley catheter placement and their propensity‐scores matched controls in the study. We evaluated urinary complications, which encompassed urinary tract cancer, urolithiasis, urethral stricture, obstructive uropathy, reflux uropathy, fistula, diverticulum, caruncle, false passage, prolapsed urethral mucosa, urinary tract rupture, and urinary tract infection. These were assessed using the Fine and Gray sub‐distribution proportional hazards model to compare between the Foley and non‐Foley groups. Sensitivity analyses were conducted with different matching ratios.
Results
In the study, the non‐Foley group presented a marginally higher mean age (75.24 ± 10.47 years) than the Foley group (74.09 ± 10.47 years). The mean duration of Foley catheterization was 6.1 ± 4.19 years. Men with Foley catheterization exhibited the highest adjusted sub‐distribution hazard ratios for urinary tract cancer (6.57, 95% CI: 5.85–7.37), followed by women with Foley catheterization (4.48, 95% CI: 3.98–5.05), and men without catheterization (1.58, 95% CI: 1.39–1.8) in comparison with women without the procedure. Furthermore, men with Foley catheterization were found to be at the greatest risk for complications such as urolithiasis, urethral stricture, obstructive and reflux uropathy, fistula, diverticulum, caruncle, false passage, prolapsed urethral mucosa, and urinary tract rupture. Conversely, women with urinary catheterization were most susceptible to urinary tract infections.
Conclusions
The evidence confirms that urinary catheterization significantly increases urinary complications, particularly among men. Our study underscores the crucial need for healthcare providers to carefully evaluate the necessity of catheterization, aim to shorten its duration whenever feasible, and strictly adhere to established protocols to minimize complications.
Abstract
Different levels of regulatory mechanisms, including posttranscriptional regulation, are needed to elaborately regulate inflammatory responses to prevent harmful effects. Terminal ...uridyltransferase 7 (TUT7) controls RNA stability by adding uridines to its 3′ ends, but its function in innate immune response remains obscure. Here we reveal that TLR4 activation induces TUT7, which in turn selectively regulates the production of a subset of cytokines, including Interleukin 6 (IL-6). TUT7 regulates IL-6 expression by controlling ribonuclease Regnase-1 mRNA (encoded by
Zc3h12a
gene) stability. Mechanistically, TLR4 activation causes TUT7 to bind directly to the stem-loop structure on
Zc3h12a
3′-UTR, thereby promotes
Zc3h12a
uridylation and degradation.
Zc3h12a
from LPS-treated TUT7-sufficient macrophages possesses increased oligo-uridylated ends with shorter poly(A) tails, whereas oligo-uridylated
Zc3h12a
is significantly reduced in
Tut7
-/-
cells after TLR4 activation. Together, our findings reveal the functional role of TUT7 in sculpting TLR4-driven responses by modulating mRNA stability of a selected set of inflammatory mediators.
The quantity and quality of peanut yields are seriously compromised by consecutive monoculture in the subtropical regions of China. Root exudates, which represent a growth regulator in peanut–soil ...feedback processes, play a principal role in soil sickness. The growth inhibition of a species in an in vitro bioassay enriched with root exudates and allelochemicals is commonly viewed as evidence of an allelopathic interaction. However, for some of these putative examples of allelopathy, the results have not been verified in more natural settings with plants continuously growing in soil. In this study, the phenolic acids in peanut root exudates, their retention characteristics in an Udic Ferrosol, and their effects on rhizosphere soil microbial communities and peanut seedling growth were studied. Phenolic acids from peanut root exudates were quickly metabolized by soil microorganisms and did not accumulate to high levels. The peanut root exudates selectively inhibited or stimulated certain communal bacterial and fungal species, with decreases in the relative abundance of the bacterial taxa Gelria glutamica, Mitsuaria chitosanitabida, and Burkholderia soli and the fungal taxa Mortierella sp. and Geminibasidium hirsutum and increases in the relative abundance of the bacterial taxon Desulfotomaculum ruminis and the fungal taxa Fusarium oxysporum, Bionectria ochroleuca and Phoma macrostoma. The experimental application of phenolic acids to non-sterile and sterile soil revealed that the poor performance of the peanut plants was attributed to changes in the soil microbial communities promoted by phenolic acids. These results suggest that pathogenic fungal accumulation at the expense of such beneficial microorganisms as plant growth promoting rhizobacteria, mycorrhizal fungi induced by root exudates, rather than direct autotoxicity induced by root exudates, might represent the principal cause underlying the soil sickness associated with peanut plants. We hope that our study will motivate researchers to integrate the role of soil microbial communities in allelopathic research, such that their observed significance in soil sickness during continuous monocropping of fields can be further explored.
•Phenolic acids were mostly metabolized by microbes rather than accumulation in soil.•Peanut root exudates increased pathogenic fungi and decreased beneficial microbes.•Pseudomonads community responded sensitively to peanut root exudates.•Bad peanut performance was due to changes of soil microbes incited by phenolic acids.
Upper tract urothelial carcinoma (UTUC), including renal, pelvic, and ureteral carcinoma, has a high incidence rate in Taiwan, which is different from that in Western countries. Therefore, it is ...imperative to elucidate the mechanisms underlying UTUC growth and metastasis. To explore the function of miR-145-5p in UTUC, we transfected the BFTC909 cell line with miR-145-5p mimics and analyzed the differences in protein levels by performing two-dimensional polyacrylamide gel electrophoresis. Real-time polymerase chain reaction and Western blot analysis were used to analyze 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inositol monophosphate cyclohydrolase (ATIC) messenger RNA and protein levels. A dual-luciferase assay was performed to identify the target of miR-145-5p in ATIC. The effects of miR-145-5p and ATIC expression by cell transfection on cell proliferation, migration, and invasion were also assessed. miR-145-5p downregulated ATIC protein expression. High ATIC expression is associated with tumor stage, metastasis, recurrence, and a poor prognosis in patients with UTUC. Cell function assays revealed that ATIC knockdown inhibited the proliferation, migration, and invasive abilities of UTUC cells. In contrast, miR-145-5p affected the proliferation, migration, and invasive abilities of UTUC cells by directly targeting the 3'-untranslated regions of ATIC. Furthermore, we used RNA sequencing and Ingenuity Pathway Analysis to identify possible downstream genes regulated by ATIC and found that miR-145-5p regulated the protein levels of fibronectin 1, Slug, cyclin A2, cyclin B1, P57, and interferon-induced transmembrane 1 via ATIC. ATIC may be a valuable predictor of prognosis and a potential therapeutic target for UTUC.
Breast cancer is a heterogeneous disease, and the survival rate of patients with breast cancer strongly depends on their stage and clinicopathological features. Chemoradiation therapy is commonly ...employed to improve the survivability of patients with advanced breast cancer. However, the treatment process is often accompanied by the development of drug resistance, which eventually leads to treatment failure. Metabolism reprogramming has been recognized as a mechanism of breast cancer resistance. In this study, we established a doxorubicin-resistant MCF-7 (MCF-7-D500) cell line through a series of long-term doxorubicin in vitro treatments. Our data revealed that MCF-7-D500 cells exhibited increased multiple-drug resistance, cancer stemness, and invasiveness compared with parental cells. We analyzed the metabolic profiles of MCF-7 and MCF-7-D500 cells through liquid chromatography−mass spectrometry. We observed significant changes in 25 metabolites, of which, 21 exhibited increased levels (>1.5-fold change and p < 0.05) and 4 exhibited decreased levels (<0.75-fold change and p < 0.05) in MCF-7 cells with doxorubicin resistance. These results suggest the involvement of metabolism reprogramming in the development of drug resistance in breast cancer, especially the activation of glycolysis, the tricarboxylic acid (TCA) cycle, and the hexamine biosynthesis pathway (HBP). Furthermore, most of the enzymes involved in glycolysis, the HBP, and the TCA cycle were upregulated in MCF-7-D500 cells and contributed to the poor prognosis of patients with breast cancer. Our findings provide new insights into the regulation of drug resistance in breast cancer, and these drug resistance-related metabolic pathways can serve as targets for the treatment of chemoresistance in breast cancer.
Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data ...analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.
A strategy was developed for synthesizing furan‐fused dibenzotropones via intramolecular Wittig reactions of alkylidene dibenzo‐β‐tropolones and acylating reactants in catalytic or stoichiometric ...conditions. With these protocols, a series of furo2,3‐fdibenzotropones were obtained in 49–99% yields within 1–10 hours. Mechanistic studies of the base‐free phenomena revealed that the organophosphane acts both as a mediator and a regenerable Brønsted base under heating.
Upper tract urothelial carcinoma (UTUC) is a rare tumor with an incidence that varies greatly between Eastern and Western countries. Transaldolase 1 (TALDO1) is a rate‐limiting enzyme of the pentose ...phosphate pathway. In humans, aberrant TALDO1 activity has been implicated in various autoimmune diseases and malignancies; however, the function of TALDO1 in UTUC has not been previously investigated. Here we evaluated the clinical significance of TALDO1 expression in 115 paraffin‐embedded tumor samples from patients with UTUC using immunohistochemistry. Our results demonstrated that there was an association between high TALDO1 expression and advanced stage (P = 0.011), tumor size (P = 0.005), tumor location (P = 0.047), distant metastases (P = 0.023), local recurrence (P = 0.002), and cancer death (P = 0.003). Using univariate and multivariate analyses, we found that chemotherapy was an independent factor for bladder recurrence‐free survival. Late stage (III/IV) and high TALDO1 expression were independent prognostic factors for progression‐free and cancer‐specific survival. In summary, increased TALDO1 expression in UTUC was significantly correlated with late stage, tumor size, tumor location, distant metastases, local recurrence, and cancer death. Therefore, high TALDO1 expression could be a predictor of poor survival in patients with UTUC. Further studies are necessary to investigate the role of TALDO1 in UTUC development.
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