BACKGROUND: This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence, featuring a unique mutation in the peroxisome proliferator-activated receptor gamma (PPARG) gene. Data Access Statement: Research data supporting this publication are available from the NN repository at www.NNN.org/download/.
METHODS: The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members. Additionally, high-throughput sequencing was conducted to analyze the PPARG genes of the patient, her siblings, and their offspring. The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy, accompanied by insulin resistance and hypertriglyceridemia. Furthermore, these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns. The results from the gene detection process demonstrated a heterozygous mutation of guanine (G) at position 284 in the coding region of exon 2 of PPARG, which replaced the base adenine (A) (exon2c.284A>Gp.Tyr95Cys). This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein. Notably, both of her siblings harbored a nucleotide heterozygous variation at the same site, and both were diagnosed with diabetes.
CONCLUSIONS: The PPARG gene mutation, particularly the p.Tyr95Cys mutation, may represent a newly identified subtype of maturity-onset diabetes of the young. This subtype is characterized by insulin resistance and lipid metabolism disorders.

OBJECTIVE: The genic male sterility (GMS) system is an important strategy for generating heterosis in plants. To better understand the essential role of lipid and sugar metabolism and to identify additional candidates for pollen development and male sterility, transcriptome and metabolome analysis of a GMS line of 1205AB in B. napus was used as a case study.
UNASSIGNED: To characterize the GMS system, the transcriptome and metabolome profiles were generated for 24 samples and 48 samples of 1205AB in B. napus, respectively. Transcriptome analysis yielded a total of 156.52 Gb of clean data and revealed the expression levels of 109,541 genes and 8,501 novel genes. In addition, a total of 1,353 metabolites were detected in the metabolomic analysis, including 784 in positive ion mode and 569 in negative ion mode.
RESULTS: A total of 15,635 differentially expressed genes (DEGs) and 83 differential metabolites (DMs) were identified from different comparison groups, most of which were involved in lipid and sugar metabolism. The combination of transcriptome and metabolome analysis revealed 49 orthologous GMS genes related to lipid metabolism and 46 orthologous GMS genes related to sugar metabolism, as well as 45 novel genes.
UNASSIGNED: The transcriptome and metabolome profiles and their analysis provide useful reference data for the future discovery of additional GMS genes and the development of more robust male sterility breeding systems for use in the production of plant hybrids.

Non-invasive diagnostics are crucial for the timely detection of renal cell carcinoma (RCC), significantly improving survival rates. Despite advancements, specific lipid markers for RCC remain unidentified. We aimed to discover and validate potent plasma markers and their association with dietary fats. Using lipid metabolite quantification, machine-learning algorithms, and marker validation, we identified RCC diagnostic markers in studies involving 60 RCC and 167 healthy controls (HC), as well as 27 RCC and 74 HC, by analyzing their correlation with dietary fats. RCC was associated with altered metabolism in amino acids, glycerophospholipids, and glutathione. We validated seven markers (l-tryptophan, various lysophosphatidylcholines [LysoPCs], decanoylcarnitine, and l-glutamic acid), achieving a 96.9% AUC, effectively distinguishing RCC from HC. Decreased decanoylcarnitine, due to reduced carnitine palmitoyltransferase 1 (CPT1) activity, was identified as affecting RCC risk. High intake of polyunsaturated fatty acids (PUFAs) was negatively correlated with LysoPC (18:1) and LysoPC (18:2), influencing RCC risk. We validated seven potential markers for RCC diagnosis, highlighting the influence of high PUFA intake on LysoPC levels and its impact on RCC occurrence via CPT1 downregulation. These insights support the efficient and accurate diagnosis of RCC, thereby facilitating risk mitigation and improving patient outcomes.

BACKGROUND: The aim of this study was to explore the correlation between biomarkers of lipid metabolism and gastric cancer.
METHODS: 1120 gastric cancer patients and 1134 health examiners enrolled in this study. The clinic data and serum lipid level, including Total cholesterol (TC), Triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C) and High-density lipoprotein cholesterol (HDL-C), were collected.
RESULTS: Serum TG and LDL-C levels in patients with gastric cancer were higher than those in the control group. HDL-C levels were lower than the control group (P < 0.05). HDL-C and LDL-C were significantly correlated with the risk of gastric cancer. Concentrating on clinicopathological features, increased TG was more frequently in male patients with distal gastric cancer, N0 stage and early TNM stage. Increased TC was more frequently in early T, N and TNM stage. Decreased HDL-C was more common in distal location and low-undifferentiated gastric cancer. LDL-C elevation was more common in distal gastric cancer and early T stage.
CONCLUSIONS: The serum lipid level of gastric cancer patients was higher than healthy controls. HDL-C and LDL-C abnormal correlated with gastric cancer risk. However, as the progresses of gastric cancer, poor patient intake, increased tumor consumption, and continuous declining in nutritional status, the levels of TC and TG gradually decreased in advanced gastric cancer.

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UNASSIGNED: This study aimed to investigate the composition of ocular surface microbiota in patients with obesity.
UNASSIGNED: This case-control study, spanning from November 2020 to March 2021 at Henan Provincial People\'s Hospital, involved 35 patients with obesity and an equivalent number of age and gender-matched healthy controls. By employing 16S rRNA sequencing, this study analyzed the differences in ocular surface microbiota between the two groups. The functional prediction analysis of the ocular surface microbiota was conducted using PICRUSt2.
UNASSIGNED: The alpha diversity showed no notable differences in the richness or evenness of the ocular surface microbiota when comparing patients with obesity to healthy controls (Shannon index, P=0.1003). However, beta diversity highlighted significant variances in the microbiota composition of these two groups (ANOSIM, P=0.005). LEfSe analysis revealed that the relative abundances of Delftia, Cutibacterium, Aquabacterium, Acidovorax, Caulobacteraceae unclassified, Comamonas and Porphyromonas in patients with obesity were significantly increased (P<0.05). Predictive analysis using PICRUSt2 highlighted a significant enhancement in certain metabolic pathways in patients with obesity, notably xenobiotics metabolism via cytochrome P450 (CYP450), lipid metabolism, and the oligomerization domain (NOD)-like receptor signaling pathway (P<0.05).
UNASSIGNED: Patients with obesity exhibit a distinct ocular surface core microbiome. The observed variations in this microbiome may correlate with increased activity in CYP450, changes in lipid metabolism, and alterations in NOD-like receptor signaling pathways.

Hyperlipidemia is characterized by elevated levels of blood lipids. The clinical manifestations are mainly atherosclerosis caused by the deposition of lipids in the vascular endothelium. The link between abnormal lipid metabolism and sudden hearing loss remains unclear. This article presents a case study of sudden hearing loss accompanied by familial hyperlipidemia. Pure tone audiometry indicated intermediate frequency hearing loss in one ear. Laboratory tests showed abnormal lipid metabolism, and genetic examination identified a heterozygous mutation in theAPOA5 gene. Diagnosis: Sudden hearing loss; hypercholesterolemia. The patient responded well to pharmacological treatment. This paper aims to analyze and discuss thepotential connection between abnormal lipid metabolism and sudden hearing loss.
摘要: 高脂血症是指血脂水平过高，临床表现主要是脂质在血管内皮沉积所引起的动脉硬化。脂代谢异常与突发性聋之间的关系尚不明确。本文报道的1例突发性聋合并家族性高胆固醇血症患者。纯音测听提示单耳中频感音性听力损失，实验室检查提示脂代谢异常，基因检测提示APOA5基因杂合突变。诊断为突发性聋；高脂血症，药物治疗效果良好。本文旨在分析总结脂代谢异常与突发性聋可能存在的联系。.

For ethical, economical, and scientific reasons, animal experimentation, used to evaluate the potential neurotoxicity of chemicals before their release in the market, needs to be replaced by new approach methodologies. To illustrate the use of new approach methodologies, the human induced pluripotent stem cell-derived 3D model BrainSpheres was acutely (48 h) or repeatedly (7 days) exposed to amiodarone (0.625-15 µM), a lipophilic antiarrhythmic drug reported to have deleterious effects on the nervous system. Neurotoxicity was assessed using transcriptomics, the immunohistochemistry of cell type-specific markers, and real-time reverse transcription-polymerase chain reaction for various genes involved in the lipid metabolism. By integrating distribution kinetics modeling with neurotoxicity readouts, we show that the observed time- and concentration-dependent increase in the neurotoxic effects of amiodarone is driven by the cellular accumulation of amiodarone after repeated dosing. The development of a compartmental in vitro distribution kinetics model allowed us to predict the change in cell-associated concentrations in BrainSpheres with time and for different exposure scenarios. The results suggest that human cells are intrinsically more sensitive to amiodarone than rodent cells. Amiodarone-induced regulation of lipid metabolism genes was observed in brain cells for the first time. Astrocytes appeared to be the most sensitive human brain cell type in vitro. In conclusion, assessing readouts at different molecular levels after the repeat dosing of human induced pluripotent stem cell-derived BrainSpheres in combination with the compartmental modeling of in vitro kinetics provides a mechanistic means to assess neurotoxicity pathways and refine chemical safety assessment for humans.

This study aims to determine the association of pregnancy cholesterol metabolism markers with gestational diabetes mellitus (GDM) risk. We performed a nested case-control study in the Tongji Birth Cohort. GDM was diagnosed according to the 75 g 2 h oral glucose tolerance test (OGTT) at 24-28 gestational weeks. Nine cholesterol metabolism markers were detected using gas chromatography-mass spectrometry. Conditional logistic regression models were conducted. A total of 444 pregnant women were matched in a 1:2 ratio. The cholestanolTC and β-sitosterolTC in cholesterol absorption markers presented negative associations with the risks of GDM (adjusted OR: 0.77, 95% CI: 0.61-0.96; adjusted OR: 0.80, 95% CI: 0.64-1.00). The desmosterolTC in cholesterol synthesis markers were positively associated with the risks of GDM (adjusted OR: 1.25, 95% CI: 1.00-1.56), similar in the ratios of cholesterol synthesis to absorption markers. After adjustment for insulin or HOMA-IR, these effects were reduced. In conclusion, higher cholesterol synthesis and lower cholesterol absorption marker levels in the first pregnancy are associated with a higher risk of GDM, and insulin resistance may play a vital role in this association.

OBJECTIVE: This report describes a rare case of acute uveitis with severe anterior chamber inflammation due to abnormal glucose and lipid metabolism.
METHODS: A 31-year-old male patient complained of redness in the right eye with decreased visual acuity for 3 days. Ocular examination revealed a milky white clouding of the right anterior chamber of the eye. Two clusters of yellowish-white exudates were visible on the surface of the iris in the upper nasal and temporal areas in addition to elevated intraocular pressure. He had a previous diagnosis of type 2 diabetes mellitus (T2DM). Laboratory tests suggested hyperlipidemia and ketoacidosis. After admission, topical glucocorticoids, mydriasis, and intraocular pressure-lowering drugs combined with hypoglycemic and lipid-lowering therapy and fluid replacement therapy were given immediately. After 10 days of treatment, the uveitis and systemic condition of the right eye were effectively controlled and improved.
CONCLUSIONS: Abnormal glucose and lipid metabolism leads to impairment of the blood-aqueous barrier, which causes a severe uveitis response in the anterior chamber. After the use of topical steroids and mydriatic eye drops combined with systemic hypoglycemic and lipid-lowering interventions, the condition was significantly relieved.