Spermidine protects cartilage from IL-1ß-mediated ferroptosis.

Rheumatoid arthritis is characterized by a burst of inflammation, the destruction of cartilage and the abundant release of inflammatory factors such as IL-1ß. Thus, the effect of IL-1ß on cartilage was examined in this study. IL-1ß could cause lipid peroxidation and disturbances in iron metabolism by increasing the expression of NCOA4 and decreasing the expression of FTH, which also induced ferritinophagy. In addition, the expression of the key antioxidant proteins SLC7A11 and GPX4 was inhibited by IL-1ß, resulting in ferroptosis in chondrocytes. Spermidine (SPD), a low-molecular-weight aliphatic nitrogen-containing compound that widely exists in animals, has been reported to be an antioxidant. In our study, we found that SPD could inhibit ferritinophagy and reverse the decrease in the expression of SLC7A11 and GPX4. Therefore, we uncovered one of the molecular mechanisms of cartilage destruction and inflammation and provide a potential polyamine for the treatment of RA.

FUS-mediated HypEVs: Neuroprotective effects against ischemic stroke.

Few studies have investigated the properties and protein composition of small extracellular vesicles (sEVs) derived from neurons under hypoxic conditions. Presently, the extent of the involvement of these plentiful sEVs in the onset and progression of ischemic stroke remains an unresolved question. Our study systematically identified the characteristics of sEVs derived from neurons under hypoxic conditions (HypEVs) by physical characterization, sEV absorption, proteomics and transcriptomics analysis. The effects of HypEVs on neurites, cell survival, and neuron structure were assessed in vitro and in vivo by neural complexity tests, magnetic resonance imaging (MRI), Golgi staining, and Western blotting of synaptic plasticity-related proteins and apoptotic proteins. Knockdown of Fused in Sarcoma (FUS) small interfering RNA (siRNA) was used to validate FUS-mediated HypEV neuroprotection and mitochondrial mRNA release. Hypoxia promoted the secretion of sEVs, and HypEVs were more easily taken up and utilized by recipient cells. The MRI results illustrated that the cerebral infarction volume was reduced by 45% with the application of HypEVs, in comparison to the non- HypEV treatment group. Mechanistically, the FUS protein is necessary for the uptake and neuroprotection of HypEVs against ischemic stroke as well as carrying a large amount of mitochondrial mRNA in HypEVs. However, FUS knockdown attenuated the neuroprotective rescue capabilities of HypEVs. Our comprehensive dataset clearly illustrates that FUS-mediated HypEVs deliver exceptional neuroprotective effects against ischemic stroke, primarily through the maintenance of neurite integrity and the reduction of mitochondria-associated apoptosis.

Multistep Dissolution of Lamellar Crystals Generates Superthin Amorphous Ni(OH)2 Catalyst for UOR.

Urea oxidation reaction (UOR) is an ideal replacement of the conventional anodic oxygen evolution reaction (OER) for efficient hydrogen production due to the favorable thermodynamics. However, the UOR activity is severely limited by the high oxidation potential of Ni-based catalysts to form Ni3+ , which is considered as the active site for UOR. Herein, by using in situ cryoTEM, cryo-electron tomography, and in situ Raman, combined with theoretical calculations, a multistep dissolution process of nickel molybdate hydrate is reported, whereby NiMoO4 ·xH2 O nanosheets exfoliate from the bulk NiMoO4 ·H2 O nanorods due to the dissolution of Mo species and crystalline water, and further dissolution results in superthin and amorphous nickel (II) hydroxide (ANH) flocculus catalyst. Owing to the superthin and amorphous structure, the ANH catalyst can be oxidized to NiOOH at a much lower potential than conventional Ni(OH)2 and finally exhibits more than an order of magnitude higher current density (640 mA cm-2 ), 30 times higher mass activity, 27 times higher TOF than those of Ni(OH)2 catalyst. The multistep dissolution mechanism provides an effective methodology for the preparation of highly active amorphous catalysts.

Melatonin suppresses bone marrow adiposity in ovariectomized rats by rescuing the imbalance between osteogenesis and adipogenesis through SIRT1 activation.

Introduction: Accelerated imbalance between bone formation and bone resorption is associated with bone loss in postmenopausal osteoporosis. Studies have shown that this loss is accompanied by an increase in bone marrow adiposity. Melatonin was shown to improve impaired bone formation capacity of bone marrow-derived mesenchymal stem cells from ovariectomized rats (OVX-BMMSCs). Objectives: To investigate whether the anti-osteoporosis effect of melatonin involves regulation of the equilibrium between osteogenic and adipogenic differentiation of osteoporotic BMMSCs. Methods: To induce osteoporosis, female Sprague-Dawley rats received ovariectomy (OVX). Primary BMMSCs were isolated from tibiae and femurs of OVX and sham-op rats and were induced towards osteogenic or adipogenic differentiation. Matrix mineralization was determined by Alizarin Red S (ARS) and lipid formation was evaluated by Oil Red O. OVX rats were injected with melatonin through the tail vein. Bone microarchitecture was determined using micro computed tomography and marrow adiposity were examined by histology staining. Results: OVX-BMMSCs exhibited a compromised osteogenic potential and an enhanced lineage differentiation towards adipocytes. In vitro melatonin improved osteogenic differentiation of OVX-BMMSCs and promoted matrix mineralization by enhancing the expression of transcription factor RUNX2 in a dose-dependent manner. Moreover, melatonin significantly inhibited lipid formation and suppressed OVX-BMMSCs adipogenesis by down-regulating peroxisome proliferator-activated receptor γ (PPARγ). Intravenous injection of melatonin prevented bone mass reduction and bone architecture destruction in ovariectomized rats. Importantly, there was a significant inhibition of adipose tissue formation in the bone marrow. Mechanistic investigations revealed that SIRT1 was involved in melatonin-mediated determination of stem cell fate. Inhibition of SIRT1 abolished the protective effects of melatonin on bone formation by inducing BMMSCs towards adipocyte differentiation. Conclusions: Melatonin reversed the differentiation switch of OVX-BMMSCs from osteogenesis to adipogenesis by activating the SIRT1 signaling pathway. Restoration of stem cell lineage commitment by melatonin prevented marrow adipose tissue over-accumulation and protected from bone loss in postmenopausal osteoporosis. The translational potential of this article: Determination of stem cell fate towards osteoblasts or adipocytes plays a pivotal role in regulating bone metabolism. This study demonstrates the protective effect of melatonin on bone mass in estrogen-deficient rats by suppressing adipose tissue accumulation in the bone marrow. Melatonin may serve as a promising candidate for the treatment of osteoporosis in clinics.

A New Nomogram for Predicting the Risk of Intracranial Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

Background: We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Methods: A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results: After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842-0.933) and 0.776 (95% CI: 0.681-0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful. Conclusions: The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.

Circular RNA circ-FoxO3 attenuates blood-brain barrier damage by inducing autophagy during ischemia/reperfusion.

Blood-brain barrier (BBB) damage can be a result of central nervous system (CNS) diseases and may be a cause of CNS deterioration. However, there are still many unknowns regarding effective and targeted therapies for maintaining BBB integrity during ischemia/reperfusion (I/R) injury. In this study, we demonstrate that the circular RNA of FoxO3 (circ-FoxO3) promotes autophagy via mTORC1 inhibition to attenuate BBB collapse under I/R. Upregulation of circ-FoxO3 and autophagic flux were detected in brain microvessel endothelial cells in patients with hemorrhagic transformation and in mice models with middle cerebral artery occlusion/reperfusion. In vivo and in vitro studies indicated that circ-FoxO3 alleviated BBB damage principally by autophagy activation. Mechanistically, we found that circ-FoxO3 inhibited mTORC1 activity mainly by sequestering mTOR and E2F1, thus promoting autophagy to clear cytotoxic aggregates for improving BBB integrity. These results demonstrate that circ-FoxO3 plays a novel role in protecting against BBB damage, and that circ-FoxO3 may be a promising therapeutic target for neurological disorders associated with BBB damage.

The Influence of Diabetes Mellitus on Patients Undergoing Primary Total Lower Extremity Arthroplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Diabetes mellitus (DM) is a common disease that has an adverse impact on most orthopedic surgeries, and its prevalence has gradually increased in recent years. We aim to investigate the influence of DM on comorbidities and complications of patients undergoing primary total lower extremity arthroplasty. METHODS: PubMed, Embase, Cochrane Library, Medline, and Web of Science were systematically searched for relevant studies published before December 2019. Demographic data, comorbidities, and postoperative complications after primary total hip arthroplasties (THA) or primary total knee arthroplasties (TKA) were assessed between DM and non-DM patients. Meta-analysis was conducted using Review Manager 5.3, and forest plots were drawn for each variable. RESULTS: A total of 1,560,461 patients (215,916 patients with DM and 1,344,545 patients without DM) from 23 studies were included in this meta-analysis. The incidences of several preoperative comorbidities (hypertension (HTN), kidney disease, cardiac and cerebrovascular disease) were generally higher in patients with DM. Moreover, DM patients had a higher rate of postoperative complications (superficial and deep infection, deep vein thrombosis (DVT), and in-hospital mortality) compared to non-DM patients. CONCLUSIONS: DM patients were more likely to suffer from comorbidities and had a higher risk of complications in total lower extremity arthroplasty compared to non-DM patients. It is necessary to identify DM and control hyperglycemia in the perioperative period to prevent postoperative complications in patients with DM.

Band Structure Engineering of Schiff-Base Microporous Organic Polymers for Enhanced Visible-Light Photocatalytic Performance.

Schiff-base networks (SBNs), as typical examples of nitrogen-doped microporous organic polymers (MOPs), exhibit promising application prospects owing to their stable properties and tunable chemical structures. However, their band structure engineering, which plays a key role in optical properties, remains elusive due to the complicated mechanisms behind energy level adjustment. In this work, a series of SBNs are fabricated by tailoring the ratio of p-phthalaldehyde and o-phthalaldehyde in the Schiff-base chemistry reaction with melamine, resulting in a straightforward as well as continuous tuning of their band gaps ranging from 4.4 to 1.4 eV. Consequently, SBNs can be successfully used as photocatalysts with excellent visible-light photocatalytic activity even under metal-free conditions. Significantly, electronic structures of SBNs are systematically studied by electrochemical and spectroscopic characterizations, demonstrating that the enhanced performance is ascribed to proper band structure and improved charge separation ability. More importantly, in combination with theoretical calculations, the band structure regulation mechanism and band structure-photocatalytic property relationship are deeply disclosed. The results obtained from this study will not only furnish SBN materials with excellent performance for solar energy conversion, but also open up elegant protocols for the molecular engineering of MOPs with desirable band structures.

Nitrogen-Enriched Carbon/CNT Composites Based on Schiff-Base Networks: Ultrahigh N Content and Enhanced Lithium Storage Properties.

To improve the electrochemical performance of carbonaceous anodes for lithium ion batteries (LIBs), the incorporation of both well-defined heteroatom species and the controllable 3D porous networks are urgently required. In this work, a novel N-enriched carbon/carbon nanotube composite (NEC/CNT) through a chemically induced precursor-controlled pyrolysis approach is developed. Instead of conventional N-containing sources or precursors, Schiff-base network (SNW-1) enables the desirable combination of a 3D polymer with intrinsic microporosity and ultrahigh N-content, which can significantly promote the fast transport of both Li+ and electron. Significantly, the strong interaction between carbon skeleton and nitrogen atoms enables the retention of ultrahigh N-content up to 21 wt% in the resultant NEC/CNT, which exhibits a super-high capacity (1050 mAh g-1 ) for 1000 cycles and excellent rate performance (500 mAh g-1 at a current density of 5 A g-1 ) as the anode material for LIBs. The NEC/CNT composite affords a new model system as well as a totally different insight for deeply understanding the relationship between chemical structures and lithium ion storage properties, in which chemistry may play a more important role than previously expected.

Human tissue kallikrein promoted activation of the ipsilesional sensorimotor cortex after acute cerebral infarction.

BACKGROUND/AIMS: Kallikrein, a serine proteinase, has been reported to have many functions, such as selectively dilating arterioles in the ischemic area and enhancing angiogenesis and neurogenesis. Therefore, it may promote cerebral poststroke reorganization. We observed the effect of human tissue kallikrein on the brain motor activation of acute ischemic stroke patients and evaluated patient condition severity and prognosis. METHODS: Forty-four cases suffering from cerebral infarction between 6 and 72 h of onset were randomly assigned into the kallikrein group (n = 24) and the control group (n = 20). The control group was given conventional treatment, whereas the kallikrein group was given both conventional treatment and human tissue kallikrein over the course of 12-14 days. The activation of the sensorimotor cortex (SMC) and cerebellum, the affected forefinger strength and the NIHSS scores were evaluated before and after treatment. The MBI and MRS scores were assessed at 30 and 90 days after stroke onset. RESULTS: There were no differences between the two groups in activation volume, patient condition and scores before treatment. After treatment, the ipsilesional SMC activation volume was significantly larger and the increase in the volume was significantly greater in the kallikrein group than in the control group (p < 0.05 for both). The NIHSS score was significantly smaller and the improvement in the score was significantly greater in the kallikrein group after treatment (p < 0.05 for both). Moreover, the MBI scores at 30 days were significantly higher, whereas the MRS scores at 30 days were significantly lower in the kallikrein group than in the control group (p < 0.05 for both). CONCLUSIONS: Kallikrein improved neural function effectively and quickly after stroke, and promoting cerebral reorganization might be an important mechanism for kallikrein in the treatment of acute cerebral infarction.