Pectolinarigenin targeting FGFR3 alleviates osteoarthritis progression by regulating the NF-κB/NLRP3 inflammasome pyroptotic pathway.

OBJECTIVE: Osteoarthritis (OA) is a chronic degenerative disease characterized by cartilage degeneration, involving inflammation, pyroptosis, and degeneration of the extracellular matrix (ECM). Pectolinarigenin (PEC) is a natural flavonoid with antioxidant, anti-inflammatory and anti-tumor properties. This study aims to explore the potential of PEC in ameliorating OA progression and its underlying mechanisms. METHODS: Chondrocytes were exposed to 10 ng/mL IL-1ß to simulate OA-like changes. The effect of PEC on IL-1ß-treated chondrocytes was assessed using ELISA, western blot, and immunofluorescence. The mRNA sequencing (mRNA-seq) was employed to explore the possible targets of PEC in delaying OA progression. The OA mouse model was induced through anterior cruciate ligament transection (ACLT) and divided into sham, ACLT, ACLT+5 mg/kg PEC, and ACLT+10 mg/kg PEC groups. Micro-computed tomography and histological analysis were conducted to confirm the beneficial effects of PEC on OA in vivo. RESULTS: PEC mitigated chondrocyte pyroptosis, as evidenced by reduced levels of pyroptosis-related proteins. Additionally, PEC attenuated IL-1ß-mediated chondrocyte ECM degradation and inflammation. Mechanistically, mRNA-seq showed that FGFR3 was a downstream target of PEC. FGFR3 silencing reversed the beneficial effects of PEC on IL-1ß-exposed chondrocytes. PEC exerted anti-pyroptotic, anti-ECM degradative, and anti-inflammatory effects through upregulating FGFR3 to inhibit the NF-κB/NLRP3 pyroptosis-related pathway. Consistently, in vivo experiments demonstrated the chondroprotective effects of PEC in OA mice. CONCLUSION: PEC alleviate OA progression by FGFR3/NF-κB/NLRP3 pathway mediated chondrocyte pyroptosis, ECM degradation and inflammation, suggesting the potential of PEC as a therapeutic agent for OA.

Effects of yeast inoculation methods on caproic acid production and microbial community during anaerobic fermentation of Chinese cabbage waste.

To provide a sufficient supply of electron donors for the synthesis of caproic acid, yeast fermentation was employed to increase ethanol production in the anaerobic fermentation of Chinese cabbage waste (CCW). The results showed that the caproic acid yield of CCW with ethanol pre-fermentation was 7750.3 mg COD/L, accounting for 50.2% of the total volatile fatty acids (TVFAs), which was 32.5% higher than that of the CCW without yeast inoculation. The synchronous fermentation of yeast and seed sludge significantly promoted the growth of butyric acid consuming bacterium Bacteroides, resulting in low yields of butyric acid and caproic acid. With yeast inoculation, substrate competition for the efficient ethanol conversion in the early stage of acidogenic fermentation inhibited the hydrolysis and acidfication. Without yeast inoculation, the rapid accumulation of TVFAs severely inhibited the growth of Bacteroidetes. In the reactor with ethanol pre-fermentation, the key microorganism for caproic acid production, Clostridium_sensu_stricto_12, was selectively enriched.

Novel annual nitrogen management strategy improves crop yield and reduces greenhouse gas emissions in wheat-maize rotation systems under limited irrigation.

Excessive irrigation and nitrogen application have long seriously undermined agricultural sustainability in the North China Plain (NCP), leading to declining groundwater tables and intensified greenhouse gas (GHG) emissions. Developing low-input management practices that meet the growing food demand while reducing environmental costs is urgently needed. Here, we developed a novel nitrogen management strategy for a typical winter wheat-summer maize rotation system in the NCP under limited irrigation (wheat sowing irrigation only (W0) or sowing and jointing irrigation (W1)) and low nitrogen input (360 kg N ha-1, about 70 % of traditional annual nitrogen input). Novel nitrogen management strategy promoted efficient nitrogen fertilizer uptake and utilization by both crops via optimization of nitrogen fertilizer allocation between the two crops, i.e., increasing nitrogen inputs to wheat (from 180 to 240 kg N ha-1) while reducing nitrogen inputs to maize (from 180 to 120 kg N ha-1). Three-year field study demonstrated that integrated management practices combining novel nitrogen management strategy with limited irrigation increased annual yields and PFPN by 1.9-5.7 %, and reduced TGE by 55-68 kg CO2-eq ha-1 and GHGI by 2.2-10.3 %, without any additional cost. Our results provide agricultural operators and policymakers with practical and easy-to-scalable integrated management strategy, and offer key initiative to promote grain production in the NCP towards agriculture sustainable intensification with high productivity and efficiency, water conservation and emission reduction.

Using Molecular Targets to Predict and Treat Aortic Aneurysms.

Aortic aneurysms are life-threatening vascular diseases associated with high morbidity, and usually require prophylactic surgical intervention. Current preventative management of aortic aneurysms relies on the diameter and other anatomic parameters of the aorta, but these have been demonstrated to be insufficient predictive factors of disease progression and potential complications. Studies on pathophysiology of aortic aneurysms could fill this need, which already indicated the significance of specific molecules in aortic aneurysms. These molecules provide more accurate prediction, and they also serve as therapeutic targets, some of which are in preclinical stage. In this review, we summarized the inadequacies and achievements of current clinical prediction standards, discussed the molecular targets in prediction and treatment, and especially emphasized the molecules that have shown potentials in early diagnosis, accurate risk assessment and target treatment of aortic aneurysm at early stage.