BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.

Melatonin alleviates early brain injury by inhibiting the NRF2-mediated ferroptosis pathway after subarachnoid hemorrhage.

Ferroptosis is a novel form of cell death that plays a critical role in the pathological and physiological processes of early brain injury following subarachnoid hemorrhage. Melatonin, as the most potent endogenous antioxidant, has shown strong protective effects against pathological changes following subarachnoid hemorrhage, but its impact on ferroptosis induced by subarachnoid hemorrhage remains unexplored. In our study, we established a subarachnoid hemorrhage model in male SD rats. We found that subarachnoid hemorrhage induced changes in ferroptosis-related indicators such as lipid peroxidation and iron metabolism, while intraperitoneal injection of melatonin (40 mg/kg) effectively ameliorated these changes to a certain degree. Moreover, in a subset of rats with subarachnoid hemorrhage who received pre-treatment via intravenous injection of the melatonin receptor antagonist Luzindole (1 mg/kg) and 4P-PDOT (1 mg/kg), we found that the protective effect of melatonin against subarachnoid hemorrhage includes inhibition of lipid peroxidation and reduction of iron accumulation depended on melatonin receptor 1B (MT2). Furthermore, our study demonstrated that melatonin inhibited neuronal ferroptosis by activating the NRF2 signaling pathway, as evidenced by in vivo inhibition of NRF2. In summary, melatonin acts through MT2 and activates NRF2 and downstream genes such as HO-1/NQO1 to inhibit ferroptosis in subarachnoid hemorrhage-induced neuronal injury, thereby improving neurological function in rats. These results suggest that melatonin is a promising therapeutic target for subarachnoid hemorrhage.

Ultracompact Vernier-effect-improved sensor by a single microfiber-knot resonator.

Fiber-optic sensors are an indispensable element of modern sensing technologies by virtue of their low cost, excellent electromagnetic immunity, and remote sensing capability. Optical Vernier effect is widely used to enhance sensitivity of fiber-optic sensors but requires bulky and complex cascaded interferometers. Here we propose and experimentally demonstrate an ultracompact (∼2 mm by ∼2 mm) Vernier-effect-improved sensor by only using a single microfiber-knot resonator. With the Vernier effect achieved by controlling the optical beating with the spectral ripple of a super light emitting diode (SLED), we show ∼20x sensitivity enhancement for quantitative temperature monitoring. Our sensor creates a new practical method to realize Vernier effect in fiber-optic sensors and beyond.

Synthesis of Bio-Based Poly(Butylene Adipate-co-Butylene Itaconate) Copolyesters with Pentaerythritol: A Thermal, Mechanical, Rheological, and Molecular Dynamics Simulation Study.

Bio-based unsaturated poly(butylene adipate-co-butylene itaconate) (PBABI) aliphatic copolyesters were synthesized with pentaerythritol (PE) as a modifier, observing the melting point, crystallization, and glass transition temperatures were decreased from 59.5 to 19.5 °C and 28.2 to -9.1 °C as an increase of itaconate concentration, and Tg ranged from -54.6 to -48.1 °C. PBABI copolyesters tend to the amorphous state by the existence of the BI unit above 40 mol%. The yield strength, elongation, and Young's modulus at different BA/BI ratios were valued in a range of 13.2-13.8 MPa, 575.2-838.5%, and 65.1-83.8 MPa, respectively. Shear-thinning behavior was obtained in all BA/BI ratios of PBABI copolyesters around an angular frequency range of 20-30 rad s-1. Furthermore, the thermal and mechanical properties of PBABI copolyesters can be well regulated via controlling the itaconic acid contents and adding the modifier. PBABI copolyesters can be coated on a 3D air mesh polyester fabric to reinforce the mechanical property for replacing traditional plaster applications.

Case study of the molecular classification and prognostic prediction of gastric cancer based on nonnegative matrix factorization / 上海交通大学学报（医学版）

Objective·To explore the molecular classification and prognostic prediction of gastric cancer based on nonnegative matrix factorization (NMF).Methods·Cases of gastric cancer were acquired from Gene Expression Omnibus (GEO). Expression profiling of lncRNA was performed by using a lncRNA-mining approach. NMF model was built with Consensus Cluster Plus package. The relationship among NMF subgroups and clinical relevance was assessed. Results·According to the molecular classification based on NMF, samples were divided into three subgroups. Significant difference was observed in relapse state, lymph node ratio, Lauren classification, TNM stage and age of onset among three subgroups. High-risk group was identified with shortest relapse time by survival analysis both in GSE62254 and GSE15459. Multivariate Cox proportional-hazards regression showed that NMF model based molecular classfication could be regarded as an independent risk factor for gastric cancer. Gene set variance analysis (GSVA) and gene set enrichment analysis (GSEA) showed that the high-risk subgroup was enriched in several tumor development pathways. Conclusion·Based on NMF model, the molecular classification of gastric cancer can be used for treatment decision and prognostic prediction.

Case study of the molecular classification and prognostic prediction of gastric cancer based on nonnegative matrix factorization / 上海交通大学学报（医学版）

Objective·To explore the molecular classification and prognostic prediction of gastric cancer based on nonnegative matrix factorization (NMF).Methods·Cases of gastric cancer were acquired from Gene Expression Omnibus (GEO). Expression profiling of lncRNA was performed by using a lncRNA-mining approach. NMF model was built with Consensus Cluster Plus package. The relationship among NMF subgroups and clinical relevance was assessed. Results·According to the molecular classification based on NMF, samples were divided into three subgroups. Significant difference was observed in relapse state, lymph node ratio, Lauren classification, TNM stage and age of onset among three subgroups. High-risk group was identified with shortest relapse time by survival analysis both in GSE62254 and GSE15459. Multivariate Cox proportional-hazards regression showed that NMF model based molecular classfication could be regarded as an independent risk factor for gastric cancer. Gene set variance analysis (GSVA) and gene set enrichment analysis (GSEA) showed that the high-risk subgroup was enriched in several tumor development pathways. Conclusion·Based on NMF model, the molecular classification of gastric cancer can be used for treatment decision and prognostic prediction.

Biomechanical study on helical long PHILOS plate fixation for proximal metaphyseal-diaphyseal humeral shaft fractures / 医用生物力学

Objective To compare biomechanical properties of the helical and straight long PHILOS (proximal humerus internal locking system) plates (Synthes Inc., Switzerland), so as to provide some biomechanical evidence for treating proximal metaphyseal-diaphyseal humeral shaft fractures in clinic. Methods Twelve Synbone artificial bones of right humerus (SYNBONE Inc., Switzerland) were divided into two groups. In control group (n=6), the humerus was fixed with the 10 hole long straight PHILOS plate, while in experimental group (n=6), the humerus was fixed with the same long PHILOS plate which was precontoured for moulding (i.e. helical PHILOS plate). After the proximal metaphyseal-diaphyseal humeral shaft fractures were made in all artificial bones, the biomechanical properties of the specimens in two groups under 6 loading modes (i.e., axial tension and compression, torsion in the same and reverse direction, medial-lateral and anterior-posterior three-point bending) were tested en bloc and compared. ResultsCompare with control group, under 100-500 N tensile and compressive loads, the axial displacement at the fractured end in experimental group increased by about 95% and 58%, respectively. Under 0.6-3 N•m torsional moment in reversed direction, the tensional angle in experimental group was obviously smaller than that in control group, with a decrease of 55%-64%. Under medial-lateral bending moment of 1.5 and 3 N•m, no significant difference was found in deflection of the experiment and control group, while under medial-lateral bending moment of 4.5, 6 and 7.5 N•m, the deflection in experimental group decreased by 20%-30% as compared to control group. Under 0.6-3 N•m torsional moment in the same direction and 1.5-7.5 N•m anterior-posterior bending moment, both the torsional angle and the deflection in experimental group were larger than those in control group, with a significant difference (P＜0.05). Compared with control group, the tensile stiffness and compressive stiffness decreased by 49% and 36%, the torsional stiffness in the same direction decreased by 19% and that in reversed direction increased by 150%, three-point bending stiffness in medial lateral direction increased by 18% and that in anterior posterior direction decreased by 70% in experimental group, all with a significant difference (P＜0.05). ConclusionsCompared with the long straight PHILO plate, the long helical PHILOS plate has better biomechanical properties, which can meet the clinical need of proximal metaphyseal-diaphyseal humeral shaft fracture fixation and postoperative rehabilitation. This surgical technique is expected to be widely applied in clinic, especially with the advantage of minimal invasive surgery.