Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.

Few population studies have sufficient follow-up period to examine early-life exposures with later life diseases. A critical question is whether involuntary exposure to tobacco smoke from conception to adulthood increases the risk of cardiometabolic diseases (CMD) in midlife. In the Collaborative Perinatal Project, serum-validated maternal smoking during pregnancy (MSP) was assessed in the 1960s. At a mean age of 39 years, 1623 offspring were followed-up for the age at first physician-diagnoses of any CMDs, including diabetes, heart disease, hypertension, or hyperlipidemia. Detailed information on their exposure to environmental tobacco smoke (ETS) in childhood and adolescence was collected with a validated questionnaire. Cox regression was used to examine associations of in utero exposure to MSP and exposure to ETS from birth to 18 years with lifetime incidence of CMD, adjusting for potential confounders. We calculated midlife cumulative incidences of hyperlipidemia (25.2%), hypertension (14.9%), diabetes (3.9%), and heart disease (1.5%). Lifetime risk of hypertension increased by the 2nd -trimester exposure to MSP (adjusted hazard ratio: 1.29, 95% confidence interval: 1.01–1.65), ETS in childhood (1.11, 0.99–1.23) and adolescence (1.22, 1.04–1.44). Lifetime risk of diabetes increased by joint exposures to MSP and ETS in childhood (1.23, 1.01–1.50) or adolescence (1.47, 1.02–2.10). These associations were stronger in males than females, in never-daily smokers than lifetime ever smokers. In conclusion, early-life involuntary exposure to tobacco smoke increases midlife risk of hypertension and diabetes in midlife.

The ordering conformation of surfactant molecules in intercalated montmorillonite prepared at various concentrations was investigated by 13C MAS NMR. The 13C MAS NMR study demonstrates the coexistence of ordered and disordered chain conformations. Two main resonance peaks are associated with the backbone alkyl chains: the resonance at 33 ppm corresponds to the ordered conformation (all-trans), and the resonance at 30 ppm corresponds to the disordered conformation (mixture of trans and gauche). Deconvolution of 13C MAS NMR spectra indicates that the ordering conformation of surfactant molecules within the gallery of montmorillonite depends very much on their orientation and packing density. When amine chains are oriented parallel to the silicate layers, the amount of all-trans conformer decreases with the increase of amine concentration. However, the amount of all-trans conformer increases with the increase of amine concentration when amine chains radiate from the silicate layers. Furthermore, 13C MAS NMR spectra show that the intercalated surfactant molecules in the clay minerals never attained the complete liquidlike or solidlike behavior.

Meat quality is not only influenced by breed but also rearing environment. The aim of this study was to evaluate the influence of different housing environments on growth performance, carcase traits, meat quality, physiological response pre-slaughter and fatty acid composition in two pig breeds. A total of 120 growing pigs at 60-70 days of age were arranged in a 2 × 2 factorial design with the breeds (Duroc × Landrace × Large White [D × L × LW] and Duroc × Landrace × Min pig [D × L × M]) and environmental enrichment (barren concrete floor or enriched with straw bedding) as factors. Each treatment was performed in triplicate with ten pigs per replicate. The pigs housed in the enriched environment exhibited a higher average daily gain, average daily feed intake, saturated fatty acid percentage and backfat depth than the pigs reared in the barren environment. Plasma cortisol levels were lower and growth hormone higher in enriched compared to barren pens. The D × L × M pigs showed lower cooking loss compared with the D × L × LW pigs. Moreover, the D × L × M pigs exhibited poor growth performance but had a better water-holding capacity. Only carcase traits and meat quality interaction effects were observed. We concluded that an enriched environment can reduce preslaughter stress and improve the growth performance of pigs and modulate the fatty acid composition of pork products.

The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.