To investigate the genetic relatedness between carbapenem-resistant Klebsiella pneumoniae(CRKP) strains isolated from intestinal colonization and subsequent bloodstream infections.

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

OBJECTIVE: To investigate the effects of methanol-ethyl acetate partitioned fractions from (MEDS) on the proliferation and apoptosis of human non-small cell lung cancer H1975 cells. METHODS: The systemic solvent extraction method was used to preliminary separation of the effective fractions in the methanol extract of . The cytotoxicity of each extract (5, 10, 20, 40, and 80 μg/mL) was tested using MTT assay. Colony cloning method was used to assess the effect of different concentrations of methanol-ethyl acetate partitioned fractions from MEDS (5, 10, 20, 40, and 80 μg/ mL) on the proliferation of H1975 cells. Flow cytometric analysis with Annexin V-FITC/PI staining was performed to detect the apoptosis of the cells after treatment with different concentrations of MEDS fractions (10, 20, and 40 μg/mL). Western blotting was used to evaluate the effects of MEDS fractions on the expressions of apoptosis-related proteins Akt, Bax, and Bcl-2. The anti-tumor activity of 100 mg/kg MEDS fractions was tested in a nude mouse model bearing H1975 cell xenografts. RESULTS: MTT assay and colony forming experiment showed that MEDS fractions significantly inhibited the proliferation of H1975 cells in a dose-and time-dependent manner ( < 0.05). The results of flow cytometry showed that MEDS fractions induced obvious apoptosis of H1975 cells in a concentration-dependent manner ( < 0.05). MEDS fractions also significantly decreased the expressions of Bcl-2 and Akt protein and increased the protein expression of Bax ( < 0.05). In the tumor-bearing nude mouse model, MEDS fractions showed potent anti-tumor effects with a low toxicity to affect the body weight and organs of the mice. CONCLUSIONS The methanol-ethyl acetate partitioned fractions from MEDS show potent anti-tumor activity both and , suggesting their value as promising therapeutic agents against lung cancer.
Acetates ; Animals ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Non-Small-Cell Lung ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Heterografts ; Humans ; Lung Neoplasms ; pathology ; Methanol ; Mice ; Mice, Nude ; Plant Extracts ; isolation & purification ; pharmacology

Objective To explore the pathological features of Aβ1-42 deposition and its correlation with Apolipoprotein E in brain of streptozotocin (STZ)-induced type Ⅱ diabetic rats.Methods High fat diet combined with small dose of STZ induced diabetic rats were adopted as experiment rats,and randomly divided into 3 months old diabetes mellitus group and 6 months old diabetes mellitus group (n=15).Healthy Wistar rats were adopted as control rats,and divided 3 months old control group and 6 months old control group (n=15).The Aβ1-42 and ApoE location and expressions were detected by immtmohistochemistry.Real-time fluorogenic quantitative-PCR and Westem blotting were used to detect the mRNA and protein levels of ApoE in each group.Results Immunohistochemical results showed that Aβ1-42 in the brain of the diabetic rats gathered around the vessel wall and blood vessel.The number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old diabetes mellitus group as compared with those in the 3 months old diabetes mellitus group (P＜0.05).The number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old control groupas compared with those in the 3 months old control group (P＜0.05).As compared with that in the 6 months old control group,the number of Aβ11-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions were significantly increased in the 6 months old diabetes mellitus group (P＜0.05).As compared with that in the 3 months old control group,the number of Aβ1-42 and ApoE positively-stained cells and positively-stained vessels was significantly larger and the ApoE mRNA and protein expressions was significantly increased in the 3 months old diabetes mellitus group (P＜0.05).Person correlation coefficient indicated that the number of positively-stained cells of Aβ-42 was positively correlated to ApoE protein expression level (r=0.9755,P=0.000).Conclusions Aβ1-42 in the brain of type Ⅱ diabetic rats expresses both in blood vessel wall and around blood vessel.Age and duration of diabetes can increase the deposition of A3 and ApoE in brain tissues,and there is a positive correlation between them.

Objective To study the tortuosity coefficient (TC) values of basilar arteries in the adult,and its change in cerebral basilar artery infarction.Methods TC values of basilar arteries was prospectively analyzed using the magnetic resonance angiography images of 135 controls(19-80 years of age,male 90,female 45)and 42 patients with cerebral infarction(5l-70 years of age,male 28,female 14).The relationship between TC values and posterior circulation infarction was statistically evaluated.Results Differences of TC between age groups were statistically significant except group B (31-50 years)and C(51-70 years)(F=10.31,P<0.01).The infarction group had greater TC value(2.497±1.200)than the control group(1.939±0.850,t=2.39,P=0.0195).Conclusions (1)Basilar artery tortuosity is positively related to age,reflecting the degree of arteriosclerosis;(2)Basilar artery tortuosity increases in patients with posterior circulation infarction.