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Three types of Zr-based metal–organic frameworks (Zr-MOFs) were employed as supports to prepare monometallic Rh catalysts by the impregnation method. The effects of the structural properties of Zr-MOFs on their supported monometallic Rh catalysts for syngas conversion were investigated. The results showed that, compared to catalysts with Rh@MOF-808 and Rh@UiO-66, Rh@UiO-67 had higher CO conversion and C2+ oxygenate selectivity. The state of the Rh site is affected by the different structure of the Zr-MOFs, which is responsible for the difference in catalytic performance. The relatively higher Rh dispersion on the UiO-67 support boosted its CO adsorption ability, and Rh@UiO-67 having the best C2+ oxygenate selectivity was mainly attributed to it having the highest Rh+/Rh0 ratio. [ABSTRACT FROM AUTHOR]

Familial partial lipodystrophy 3 (FPLD3) is a rare genetic disorder caused by loss-of-function mutations in the PPARG gene, characterized by a selective absence of subcutaneous fat and associated metabolic complications. However, the molecular mechanisms of FPLD3 remain unclear. In this study, we recruited a 17-yr-old Chinese female with FPLD3 and her family, identifying a novel PPARG frameshift mutation (exon 4: c.418dup: p.R140Kfs*7) that truncates the PPARγ protein at the seventh amino acid, significantly expanding the genetic landscape of FPLD3. By performing next-generation sequencing of circular RNAs (circRNAs), microRNAs (miRNAs), and mRNAs in plasma exosomes, we discovered 59 circRNAs, 57 miRNAs, and 299 mRNAs were significantly altered in the mutation carriers compared with the healthy controls. Integration analysis highlighted that the circ_0001597-miR-671-5p pair and 18 mRNAs might be incorporated into the metabolic regulatory networks of the FPLD3 induced by the novel PPARG mutation. Functional annotation suggested that these genes were significantly enriched in glucose- and lipid metabolism-related pathways. Among the circRNA-miRNA-mRNA network, we identified two critical regulators, early growth response-1 (EGR1), a key transcription factor known for its role in insulin signaling pathways and lipid metabolism, and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), which gets involved in the biosynthesis of triglycerides and lipolysis. Circ_0001597 regulates the expression of these genes through miR-671-5p, potentially contributing to the pathophysiology of FPLD3. Overall, this study clarified a circulating exosomal circRNA-miRNA-mRNA network in a FPLD3 family with a novel PPARG mutation, providing evidence for exploring promising biomarkers and developing novel therapeutic strategies for this rare genetic disorder. NEW & NOTEWORTHY: Through the establishment of a ceRNA regulatory networks in a novel PPARG frameshift mutation c.418dup-induced FPLD3 pedigree, this study reveals that circ_0001597 may contribute to the pathophysiology of FPLD3 by sequestering miR-671-5p to regulate the expression of EGR1 and AGPAT3, pivotal genes situated in the triglyceride (TG) synthesis and lipolysis pathways. Current findings expand our molecular understanding of adipose tissue dysfunction, providing potential blood biomarkers and therapeutic avenues for lipodystrophy and associated metabolic complications. [ABSTRACT FROM AUTHOR]

Aims: The incidence of type 2 diabetes in China has exhibited an increasing trend, including younger individuals, over the past years. Early‐onset type 2 diabetes (EOT2D) refers to diabetes diagnosed before 40 years of age. These patients have poor metabolic control and are highly susceptible to diabetic complications, which poses challenges for treatment. However, few studies have reported on the treatment of EOT2D. We determined clinical features and trends in drug use in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: This retrospective study was performed at the Endocrinology Ward, Peking Union Medical College Hospital (PUMCH). "Diabetes" was used when searching PUMCH's Electronic Medical Record Analytical Database to obtain clinical data of patients between January 2013 and May 2022. Results: The analysis included 1590 patients with T2DM. Among them, 609 (38.3%) had EOT2D. Compared with late‐onset type 2 diabetes (LOT2D) patients, EOT2D patients exhibited worse glycemic control and higher body weight and lipid levels despite significant age differences. EOT2D patients also had a higher risk of diabetic retinopathy and nephropathy. Under the general trend of increasing use of dipeptidylpeptidase‐4 inhibitors, sodium‐glucose cotransporter‐2 inhibitors, and glucagon‐like peptide‐1 agonists, patients with EOT2D were more likely to use organ‐protective drugs. Conclusions: Compared with LOT2D patients, EOT2D patients have a longer course of diabetes, worse metabolic control, and a higher rate of developing microvascular complications. The administration of combined therapy, including new agents, may require consideration when selecting hypoglycemic agents for treating EOT2D. [ABSTRACT FROM AUTHOR]

Dysregulated lineage commitment of mesenchymal stem cells (MSCs) contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis. The intrinsic cellular mechanism that regulates MSC commitment remains unclear. Here, we identified Cullin 4B (CUL4B) as a critical regulator of MSC commitment. CUL4B is expressed in bone marrow MSCs (BMSCs) and downregulated with aging in mice and humans. Conditional knockout of Cul4b in MSCs resulted in impaired postnatal skeletal development with low bone mass and reduced bone formation. Moreover, depletion of CUL4B in MSCs aggravated bone loss and marrow adipose accumulation during natural aging or after ovariectomy. In addition, CUL4B deficiency in MSCs reduced bone strength. Mechanistically, CUL4B promoted osteogenesis and inhibited adipogenesis of MSCs by repressing KLF4 and C/EBPδ expression, respectively. The CUL4B complex directly bound to Klf4 and Cebpd and epigenetically repressed their transcription. Collectively, this study reveals CUL4B-mediated epigenetic regulation of the osteogenic or adipogenic commitment of MSCs, which has therapeutic implications in osteoporosis. [ABSTRACT FROM AUTHOR]

Background: This study aims to develop and validate an artificial intelligence (AI)-aided Prostate Imaging Reporting and Data System (PI-RADSAI) for prostate cancer (PCa) diagnosis based on MRI. Methods: The deidentified MRI data of 1540 biopsy-naïve patients were collected from four centres. PI-RADSAI is a two-stage, human-in-the-loop AI capable of emulating the diagnostic acumen of subspecialists for PCa on MRI. The first stage uses a UNet-Seg model to detect and segment biopsy-candidate prostate lesions, whereas the second stage leverages UNet-Seg segmentation is trained specifically with subspecialist' knowledge-guided 3D-Resnet to achieve an automatic AI-aided diagnosis for PCa. Results: In the independent test set, UNet-Seg identified 87.2% (628/720) of target lesions, with a Dice score of 44.9% (range, 22.8–60.2%) in segmenting lesion contours. In the ablation experiment, the model trained with the data from three centres was superior (kappa coefficient, 0.716 vs. 0.531) to that trained with single-centre data. In the internal and external tests, the triple-centre PI-RADSAI model achieved an overall agreement of 58.4% (188/322) and 60.1% (92/153) with a referential subspecialist in scoring target lesions; when one-point margin of error was permissible, the agreement rose to 91.3% (294/322) and 97.3% (149/153), respectively. In the paired test, PI-RADSAI outperformed 5/11 (45.5%) and matched the performance of 3/11 (27.3%) general radiologists in achieving a clinically significant PCa diagnosis (area under the curve, internal test, 0.801 vs. 0.770, p < 0.01; external test, 0.833 vs. 0.867, p = 0.309). Conclusions: Our closed-loop PI-RADSAI outperforms or matches the performance of more than 70% of general readers in the MRI assessment of PCa. This system might provide an alternative to radiologists and offer diagnostic benefits to clinical practice, especially where subspecialist expertise is unavailable. [ABSTRACT FROM AUTHOR]

Plasmid-mediated conjugation is a common mechanism for most bacteria to transfer antibiotic resistance genes (ARGs). The conjugative transfer of ARGs is emerging as a major threat to human beings. Although several transfer-related factors are known to regulate this process, small RNAs (sRNAs)-based regulatory roles remain to be clarified. Here, the Hfq-binding sRNA GadY in donor strain Escherichia coli ( E. coli ) SM10λπ was identified as a new regulator for bacterial conjugation. Two conjugation models established in our previous studies were used, which SM10λπ carrying a chromosomally integrated IncP-1α plasmid RP4 and a mobilizable plasmid pUCP24T served as donor cells, and P. aeruginosa PAO1 or E. coli EC600 as the recipients. GadY was found to promote SM10λπ-PAO1 conjugation by base-pairing with its target mRNA SdiA, an orphan LuxR-type receptor that responds to exogenous N-acylated homoserine lactones (AHLs). However, SM10λπ-EC600 conjugation was not affected due to EC600 lacking AHLs synthase. It indicates that the effects of GadY on conjugation depended on AHLs-SdiA signalling. Further study found GadY bound SdiA to negatively regulate the global RP4 repressors KorA and KorB. When under ciprofloxacin or levofloxacin treatment, GadY expression in donor strain was enhanced, and it positively regulated quinolone-induced SM10λπ-PAO1 conjugation. Thus, our study provides a novel role for sRNA GadY in regulating plasmid-mediated conjugation, which helps us better understand bacterial conjugation to counter antibiotic resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Long, Li, Li, Yu, Lu, Ma, Cai, Shen, Zeng, Huang, Chen and Pu.)