Controllable integration of nano zero-valent iron into MOFs with different structures for the purification of hexavalent chromium-contaminated water: Combined insights of scavenging performance and potential mechanism investigations.

This work combined the stability of the porous structure of metal-organic frameworks with the strong reducibility of nano zero-valent iron, for the controllable integration of NZVI into MOFs to utilize the advantages of each component with enhancing the rapid decontamination and scavenging of Cr(VI) from wastewater. Hence, four kinds of MOFs/NZVI composites namely ZIF67/NZVI, MOF74/NZVI, MIL101(Fe)/NZVI, CuBTC/NZVI, were prepared for Cr(VI) capture. The results indicated that the stable structure of ZIF67, MOF74, MIL101(Fe), CuBTC, was beneficial for the dispersion of NZVI that could help more close contact between MOFs/NZVI reactive sites and Cr(VI), subsequently, MOFs/NZVI was proved to be better scavengers for Cr(VI) scavenging than NZVI alone. The Cr(VI) capture achieved the maximum adsorption capacity at pH ~ 4.0, which might be due to the participation of more H+ in the reaction and better corrosion of NZVI at lower pH. Mechanism investigation demonstrated synergy of adsorption, reduction and surface precipitation resulted in enhanced Cr(VI) scavenging, and Fe(0), dissolved and surface-bound Fe(II) were the primary reducing species. The findings of this investigation indicated that the as-prepared composites of ZIF67/NZVI, MOF74/NZVI, MIL101(Fe)/NZVI, CuBTC/NZVI, with high oxidation resistance and excellent reactivity, could provide reference for the decontamination and purification of actual Cr(VI)-containing wastewater.

Overexpressing of the GIPC1 protects against pathological cardiac remodelling.

OBJECTIVE: Pathological cardiac remodelling, including cardiac hypertrophy and fibrosis, is a key pathological process in the development of heart failure. However, effective therapeutic approaches are limited. The ß-adrenergic receptors are pivotal signalling molecules in regulating cardiac function. G-alpha interacting protein (GAIP)-interacting protein, C-terminus 1 (GIPC1) is a multifunctional scaffold protein that directly binds to the C-terminus of ß1-adrenergic receptor (ß1-adrenergic receptor). However, little is known about its roles in heart function. Therefore, we investigated the role of GIPC1 in cardiac remodelling and its underlying molecular mechanisms. METHODS: Pathological cardiac remodelling in mice was established via intraperitoneal injection of isoprenaline for 14 d or transverse aortic constriction surgery for 8 weeks. Myh6-driving cardiomyocyte-specific GIPC1 conditional knockout (GIPC1 cKO) mice and adeno-associated virus 9 (AAV9)-mediated GIPC1 overexpression mice were used. The effect of GIPC1 on cardiac remodelling was assessed using echocardiographic, histological, and biochemical analyses. RESULTS: GIPC1 expression was consistently reduced in the cardiac remodelling model. GIPC1 cKO mice exhibited spontaneous abnormalities, including cardiac hypertrophy, fibrosis, and systolic dysfunction. In contrast, AAV9-mediated GIPC1 overexpression in the heart attenuated isoproterenol-induced pathological cardiac remodelling in mice. Mechanistically, GIPC1 interacted with the ß1-adrenergic receptor and stabilised its expression by preventing its ubiquitination and degradation, maintaining the balance of ß1-adrenergic receptor/ß2-adrenergic receptor, and inhibiting hyperactivation of the mitogen-activated protein kinase signalling pathway. CONCLUSIONS: These results suggested that GIPC1 plays a cardioprotective role and is a promising therapeutic target for the treatment of cardiac remodelling and heart failure.

Role of the Paraspinal Muscles in the Sagittal Imbalance Cascade: The Effects of Their Endurance and of Their Morphology on Sagittal Spinopelvic Alignment.

BACKGROUND: The role of paraspinal muscle degeneration in the cascade of sagittal imbalance is still unclear. This study aimed to compare paraspinal muscle degeneration in the 4 stages of sagittal imbalance: sagittal balance (SB), compensated sagittal balance (CSB), decompensated sagittal imbalance (DSI), and sagittal imbalance with failure of pelvic compensation (SI-FPC). In addition, it aimed to compare the effects paraspinal muscle endurance and morphology on sagittal spinopelvic alignment in patients with lumbar spinal stenosis. METHODS: A cross-sectional study of 219 patients hospitalized with lumbar spinal stenosis was performed. The isometric paraspinal extensor endurance test and evaluation of atrophy and fat infiltration of the paraspinal extensor muscles and psoas major on magnetic resonance imaging were performed at baseline. Spinopelvic parameters including lumbar lordosis, pelvic tilt, sacral slope, pelvic incidence, and the sagittal vertical axis were measured. RESULTS: The patients with lumbar spinal stenosis were divided into 67 with SB, 85 with CSB, 49 with DSI, and 17 with SI-FPC. There were significant differences in paraspinal muscle endurance and morphology among the 4 groups. Furthermore, the SI-FPC group had poorer paraspinal muscle endurance than either the SB or the CSB group. In multiple linear regression analysis, paraspinal muscle endurance and the relative functional cross-sectional area of the paraspinal extensor muscles were the independent predictors of the sagittal vertical axis, and the relative functional cross-sectional area of the psoas major was the independent predictor of relative pelvic version. CONCLUSIONS: This study indicated that paraspinal muscle degeneration is not only an initiating factor in pelvic retroversion but also a risk factor for progression from a compensated to a decompensated stage. Specifically, the impairment of muscle endurance in the CSB stage may be the reason why patients experience failure of pelvic compensation. In addition, paraspinal muscle endurance and muscle morphology (relative functional cross-sectional area of the paraspinal extensor muscles and psoas major) had different clinical consequences. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Does paraspinal muscle morphometry predict functional status and re-operation after lumbar spinal surgery? A systematic review and meta-analysis.

OBJECTIVES: Whether paraspinal muscle degeneration is related to poor clinical outcomes after lumbar surgery is still indistinct, which limits its clinical application. This study aimed to evaluate the predictive value of paraspinal muscle morphology on functional status and re-operation after lumbar spinal surgery. METHODS: A review of the literature was conducted using a total of 6917 articles identified from a search of PubMed, EMBASE, and Web of Science databases through September 2022. A full-text review of 140 studies was conducted based on criteria including an objective assessment of preoperative paraspinal muscle morphology including multifidus (MF), erector spinae (ES), and psoas major (PS) in addition to measuring its relationship to clinical outcomes including Oswestry disability index (ODI), pain and revision surgery. Meta-analysis was performed when required metrics could be calculated in ≥ three studies, otherwise vote counting model was a good alternative to show the effect direction of evidence. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated. RESULTS: A total of 10 studies were included in this review. Of them, five studies with required metrics were included in the meta-analysis. The meta-analysis suggested that higher preoperative fat infiltration (FI) of MF could predict higher postoperative ODI scores (SMD = 0.33, 95% CI 0.16-0.50, p = 0.0001). For postoperative pain, MF FI could also be an effective predictor for persistent low back pain after surgery (SMD = 0.17, 95% CI 0.02-0.31, p = 0.03). However, in the vote count model, limited evidence was presented for the prognostic effects of ES and PS on postoperative functional status and symptoms. In terms of revision surgery, there was conflicting evidence that FI of MF and ES could predict the incidence of revision surgery in the vote count model. CONCLUSION: The assessment of MF FI could be a viable method to stratify patients with lumbar surgery by the risk of severe functional disability and low back pain. KEY POINTS: • The fat infiltration of multifidus can predict postoperative functional status and low back pain after lumbar spinal surgery. • The preoperative evaluation of paraspinal muscle morphology is conducive for surgeons.

Clioquinol induces autophagy by down-regulation of calreticulin in human neurotypic SH-SY5Y cells.

Clioquinol (CQ) is considered as a promising drug of neurodegenerative diseases. However, the underlying mechanism is unclear. Our previous study has proved that CQ induces S-phase cell cycle arrest through the elevation of intracellular calcium concentration ([Ca2+]i) with high levels of SERCA2. Furthermore, it could induce autophagy in an intracellular calcium independent manner in human neurotypic SH-SY5Y cells. In this study, the involvement of calreticulin (CRT) in autophagy induced by CQ was investigated. Our results illustrated the endoplasmic reticulum (ER) stress induced by CQ and DTT led to the cell death in different manners. DTT, an ER stress positive control, induced UPR accompanied with up-regulation of CRT and apoptosis, while CQ inhibited UPR accompanied with down-regulation of CRT，resulting in autophagy. Then, overexpression of CRT was shown to cause UPR and decrease [Ca2+]i, leading to cell apoptosis and inhibition of S-phase arrest induced by CQ. While the UPR was alleviated and autophagy was further enhanced in CRT deficient cells by using targeted siRNA. Meanwhile, down-regulation of CRT resulted in [Ca2+]i overload and induction of S-phase arrest. Finally, we found that the effect of CQ on the HT22 cells was similar to that on the SH-SY5Y cells. Our data showed for the first time that CQ decreased expression of CRT, leading to autophagy, an increase of [Ca2+]i, and cell S-phase arrest in the neurotypic cells. The present study describes the cellular signal pathways regulating autophagy by CQ and highlights the potential therapeutic application of CQ in neurodegenerative disorders.