Targeting ferroptosis in neuroimmune and neurodegenerative disorders for the development of novel therapeutics.

Neuroimmune and neurodegenerative ailments impose a substantial societal burden. Neuroimmune disorders involve the intricate regulatory interactions between the immune system and the central nervous system. Prominent examples of neuroimmune disorders encompass multiple sclerosis and neuromyelitis optica. Neurodegenerative diseases result from neuronal degeneration or demyelination in the brain or spinal cord, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. The precise underlying pathogenesis of these conditions remains incompletely understood. Ferroptosis, a programmed form of cell death characterised by lipid peroxidation and iron overload, plays a pivotal role in neuroimmune and neurodegenerative diseases. In this review, we provide a detailed overview of ferroptosis, its mechanisms, pathways, and regulation during the progression of neuroimmune and neurodegenerative diseases. Furthermore, we summarise the impact of ferroptosis on neuroimmune-related cells (T cells, B cells, neutrophils, and macrophages) and neural cells (glial cells and neurons). Finally, we explore the potential therapeutic implications of ferroptosis inhibitors in diverse neuroimmune and neurodegenerative diseases.

Case report of 18F-FDG PET/CT features of hypoglycemic encephalopathy.

RATIONALE: Hypoglycemia may cause diverse neurological manifestations, ranging from focal neurological deficits to irreversible coma. Severe and persistent hypoglycemia can lead to hypoglycemic encephalopathy (HE). Imaging findings of HE at different stages of 18F-FDG positron emission tomography/computed tomography (PET/CT) have rarely been reported. Herein, we describe a case of HE occurring in the medial frontal cortex, cerebellar cortex, and dentate nucleus using 18F-FDG PET/CT images from different periods. 18F-FDG PET/CT has a high value in displaying the lesion range and indicating the prognosis. PATIENT CONCERNS: A 57-year-old male patient with type 2 diabetes (T2D) was transferred to the hospital with a history of unconsciousness for 1 night. The patient showed a significant decrease in blood glucose levels. DIAGNOSES: The patient was initially diagnosed with a hypoglycemic coma. INTERVENTIONS: The patient subsequently underwent a comprehensive treatment. The 18F-FDG PET/CT examination on the fifth day after admission revealed a significant symmetrical fluorodeoxyglucose (FDG)-positive accumulation in the bilateral medial frontal gyrus, cerebellar cortex, and dentate nucleus. A follow-up PET/CT examination 6 months later revealed hypometabolism in the bilateral medial frontal gyrus and no abnormalities in FDG uptake in the bilateral cerebellar cortex and dentate nucleus. OUTCOMES: The patient condition was stable 6 months later, with a slow response, memory deterioration, occasional dizziness, and episodes of hypoglycemia. LESSONS: HE lesions with a high metabolic status may be related to a metabolic compensation mechanism in response to gray matter loss. Some of the more severely damaged cells eventually die even after the blood sugar levels return to normal. Less damaged nerve cells can be recovered. 18F-FDG PET/CT has high value in indicating the lesion range and prognosis of HE.

Constructing Nanocaged Enzymes for Synergistic Catalysis of CO2 Reduction.

Promoting the activity of biological enzymes under in vitro environment is a promising technique for bioelectrocatalytic reactions, such as the conversion of carbon dioxide (CO2 ) into valuable chemicals, which is a promising strategy to address the environmental issue of CO2 in the atmosphere; however, this technique remains challenging. Herein, a nanocage structure for enzyme confinement is synthesized to enable the in situ encapsulation of formate dehydrogenase (FDH) in a porous metal-organic framework, which acts as a coenzyme and boosts the hybrid synergistic catalysis using enzymes. This study reveals that the synthesized FDH@ZIF-8 nanocage-structured hybrid (CSH) catalyst exhibits an improved catalytic ability of the enzymes and increases the hydrophobicity of the electrode and its affinity to CO2 . Thus, CSH can trap CO2 and control its microenvironments. The CSH catalyst boosts the conversion rate of CO2 to formic acid (HCOOH) to 28 times higher than that when using pure FDH. The in situ attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) spectra indicates that OCHO* is the key intermediate. Density functional theory (DFT) calculations show that CSH has extremely low overpotential and is particularly effective for producing formate. This protection architecture for enzymes considerably promotes their biological application under in vitro environments.

Tin-based metal organic framework catalysts for high-efficiency electrocatalytic CO2 conversion into formate.

Electrochemical reduction of carbon dioxide (ERCO2) allows for the conversion of CO2 to value-added low-carbon chemicals. Catalysts are indispensable for an efficient ERCO2 process. In this work, a Sn-based metal-organic framework (Sn-MOF) was synthesized as an electrocatalyst for the conversion of CO2 to formate (HCOO-). Such a Sn-MOF electrocatalyst exhibits an outstanding performance with a formate selectivity up to 92% and a current density of 23.2 mA cm-2 at -1.2 VRHE. Density functional theory calculations were used to probe and analyze the catalytic ERCO2 mechanism. This work shows the possibility to achieve a high efficiency of a pure Sn-MOF in catalyzing ERCO2 directly. In addition, this work provides insights into the design and synthesis of highly efficient ERCO2 electrocatalysts for practical applications.

Confinement-Induced Catalytic Dissociation of Hydrogen Molecules in a Scanning Tunneling Microscope.

The catalytic scission of single chemical bonds has been induced by the nanoscale confinement in a scanning tunneling microscope (STM) junction. Individual hydrogen molecules sandwiched between the STM tip and a copper substrate can be dissociated solely by the reciprocating movement of the tip. The reaction rate depends sensitively on the local molecular environment, as exemplified by the effects of a nearby carbon monoxide molecule or a gold adatom. Detailed mechanisms and the nature of the transition states are revealed by density functional theory (DFT) calculations. This work provides insights into chemical reactions at the atomic scale induced by localized confinement applied by the STM tip. Furthermore, a single diatomic molecule can act as a molecular catalyst to enhance the reaction rate on a surface.

Engineering Steam Induced Surface Oxygen Vacancy onto Ni-Fe Bimetallic Nanocomposite for CO2 Electroreduction.

Surface oxygen vacancies (Vo ) regulation is an effective strategy to improve the electrochemical CO2  reduction reaction (CO2 RR) performance by lowering the activation energy barrier of CO2 ; however, the lack of precise control over the local atomic structures severely hinders the large-scale application of Vo -activated electrocatalyst for CO2 RR. Herein, an efficient strategy to facilitate CO2  activation is developed by introducing Vo into transition metal nanoparticles (NPs) with a steam-assisted chemical vapor deposition method. With the steam process, abundant surface Vo are introduced into the assembled Ni-Fe bimetallic NPs composite (H-NiFe/NG), which adjust surface Ni/Fe atoms to low-valent coordinatively unsaturated Ni (+1)/Fe (+2) sites, serving as electron-rich centers to adsorb and activate inert CO2  molecules. The as-prepared H-NiFe/NG composite exhibits excellent catalytic performance with a maximum Faradaic efficiency of 94% at -0.80 V (vs RHE) for CO production with remarkable stability. The density function theory calculations corroborate that the Ni atoms around surface Vo significantly lower the energy barrier for COOH* intermediate formation, which gives a low overpotential for reducing CO2  to CO, exhibiting superior CO2 RR performance. This general synthetic strategy provides a new insight to introduce surface Vo on transition metal for efficient CO2  reduction.

Achieving high selectivity towards electro-conversion of CO2 using In-doped Bi derived from metal-organic frameworks.

Metal-organic frameworks (MOFs) and their derivatives have shown great potential as electrocatalysts, in virtue of their ease of functionalization and abundance of active sites. Here, we report a series of indium-doped bismuth MOF-derived composites (BiInX-Y@C) for the direct conversion of carbon dioxide (CO2) to hydrocarbon derivatives. Amongst the catalysts studied, BiIn5-500@C demonstrated high selectivity for the production of formate and intrinsic activity in a wide potential window, ranging from - 1.16 to - 0.76 V vs. RHE (VRHE). At - 0.86 VRHE, the Faradaic efficiency and total current density were determined as 97.5% and - 13.5 mA cm-2, respectively. In addition, a 15-h stability test shows no obvious signs of deactivation. Complementary density functional theory (DFT) calculations revealed that the In-doped Bi2O3 are the predominant active centers for HCOOH production in the reduction of CO2 under the action of the BiInX-Y@C catalyst. This work provides new detailed insights into reaction mechanism, and selectivity for reduction of CO2via MOFs, which are expected to inspire and guide the design of novel, selective and efficient catalysts.

Safety of Recanalization Therapy in Acute Ischemic Stroke Patients on Direct Oral Anticoagulant Therapy: An Updated Systematic Review and Meta-Analysis.

This review provides an updated assessment of the safety of recanalization therapy for Acute Ischemic Stroke (AIS) patients receiving direct oral anticoagulants (DOAC) therapy. We checked the literature for published observational from 1st January 1950 to 31st March 2021. The rate of symptomatic intracerebral hemorrhage (sICH), arterial recanalization rate, good functional recovery, and mortality at 3 months were investigated, and data were expressed as Risk ratio (RR) with a 95% confidence interval (CI). Publication bias, sensitivity analysis, and meta-regression analyses were conducted utilizing STATA software. 17 articles [14 for endovascular therapy (EVT) and 3 intravenous thrombolysis for (IVT)] were finally included in the review. AIS patients with DOAC therapy showed a decreased rate of sICH (RR = 0.85, 95% CI = 0.72 to 1.00, P = 0.04), and lower probability of good functional recovery at three months (RR = 0.79, 95% CI = 0.73 to 0.85, P < 0.001) than patients without anticoagulation therapy post EVT. However, no significant differences in sICH rates in AIS patients with DOAC therapy after IVT (RR = 0.87, 95% CI = 0.48 to 1.58, P = 0.64) were observed. AIS patients not prescribed DOAC after EVT had a higher mortality risk (RR = 1.29, 95% CI = 1.15-1.44, P < 0.001). Patients with AIS on DOAC therapy were found to have a lower incidence of sICH following EVT. However, no evidence of an increased bleeding risk in patients previously treated with DOAC after IVT was observed. Therefore, more detailed studies with biological data to monitor compliance and details on the size and etiology/severity of the incident ischemic lesion is needed.

Characteristics and Outcomes of Intravenous Thrombolysis in Mild Ischemic Stroke Patients.

Objective: This study assessed the characteristics of intravenous thrombolysis (IVT) with respect to early neurological deterioration (END) and functional outcome in mild ischemic stroke patients. Methods: Data were obtained from acute mild ischemic stroke patients (defined as having a National Institute of Health Stroke Score (NIHSS) ≤ 5) treated with IVT in our hospital from July 2017 to December 2020. END was defined as the NIHSS increased ≥1 over the baseline at 24 h after IVT. A modified Rankin scale (mRS) ≤ 1 at 3 months was considered as a favorable outcome, and an mRS ≥2 at 3 months was an unfavorable outcome. Results: Two hundred thirty-three acute mild ischemic stroke patients (all patients underwent MRI and DWI restriction) with IVT were included in this study. Thirty-one patients experienced END, and 57 patients experienced an unfavorable outcome at 3 months. With multivariate analysis, END was associated with an elevated baseline systolic blood pressure (SBP) (OR = 1.324, 95% CI, 1.053-1.664, p = 0.016) and coronary heart disease (OR = 4.933, 95% CI, 1.249-19.482, p = 0.023). An unfavorable outcome at 3 months after IVT was independently associated with a baseline elevated SBP (OR = 1.213, 95% CI, 1.005-1.465, p = 0.045), baseline NIHSS (OR = 1.515, 95% CI, 1.186-1.935, p = 0.001), prior hyperlipemia (OR = 3.065, 95% CI, 1.107-8.482, p = 0.031), cardioembolic stroke (OR = 0.323, 95% CI, 0.120-0.871, p = 0.025), and END at 24 h (OR = 4.531, 95% CI, 1.950-10.533, p < 0.001) in mild ischemic stroke patients. Conclusion: In mild ischemic stroke patients with IVT, an elevated baseline SBP and coronary heart disease were associated with END. The elevated baseline SBP, baseline NIHSS, a history of prior hyperlipemia, cardioembolic stroke, and END at 24 h after IVT were useful in predicting an unfavorable outcome at 3 months.

Au3+ Species Boost the Catalytic Performance of Au/ZnO for the Semi-hydrogenation of Acetylene.

Au nanoparticles have garnered remarkable attention in the chemoselective hydrogenation due to their extraordinary selectivity. However, the activity is far from satisfactory. Knowledge of the structure-performance relationship is a key prerequisite for rational designing of highly efficient Au-based hydrogenation catalysts. Herein, diverse Au sites were created through engineering their interactions with supports, specifically via adjusting the support morphology, that is, flower-like ZnO (ZnO-F) and disc-like ZnO (ZnO-D), and the catalyst pretreatment atmosphere, that is, 10 vol % O2/Ar and 10 vol % H2/Ar (denoted as -O and -H, respectively). The four samples of Au/ZnO were characterized by various techniques and evaluated in the semi-hydrogenation of acetylene. The transmission electron microscopy results indicated that the Au particle sizes are almost similar for our Au/ZnO catalysts. The charge states of Au species demonstrated by X-ray photoelectron spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy with CO as the probe molecule, and simulation based on density functional theory, however, are greatly dependent on the ZnO shape and pretreatment atmosphere, that is, the percentage of Au3+ reduces following the order of Au/ZnO-F-O > Au/ZnO-F-H > Au/ZnO-D-O > Au/ZnO-D-H. The testing results showed that the Au/ZnO-F-O catalyst containing maximum of Au3+ possesses the optimal activity with 1.8 × 10-2 s-1 of specific activity at 200 °C, around 16.5-fold of that for Au/ZnO-D-H. More interestingly, the specific rate at 200 °C and the average conversion/selectivity in the entire operating temperature range are well correlated with the redox states of the Au species, indicating that Au3+ sites are more active for acetylene hydrogenation. A plausible explanation is that the Au3+ species not only facilitate acetylene adsorption via electrostatic interactions but also favor the heterolysis of H2 via constructing frustrated Lewis pairs with O.

Clinical laboratory characteristics of patients with obstructive jaundice accompanied by dyslipidemia.

BACKGROUND: Abnormal lipid metabolism manifests as hypercholesterolemia in patients with obstructive jaundice due to lipoprotein X (LpX). Our aim was to explore the clinical laboratory characteristics of patients with obstructive jaundice accompanied by dyslipidemia in a large number of samples. METHODS: A total of 665 patients with obstructive jaundice were included and categorized into two groups (with/without dyslipidemia) based on the ratio of the sum of HDL-c and LDL-c to total cholesterol [(HDL-c + LDL-c)/TC] with a cut-off value of 0.695. Laboratory liver, kidney, and blood lipid parameters were determined. Cholesterol composition assessment was performed by ultracentrifugation and high-performance liquid chromatography (UC-HPLC), and serum protein profiles were analyzed by capillary electrophoresis. RESULTS: Liver function in patients with obstructive jaundice accompanied by dyslipidemia was more aggravated than that in patients with simple obstructive jaundice (P < 0.05). The (HDL-c + LDL-c)/TC ratio was negatively correlated with bilirubin levels (P < 0.05). In addition, the difference in ApoB/LDL-c ratios was statistically significant between the obstructive jaundice accompanied by dyslipidemia group and healthy control group (P < 0.05). The LDL-c concentration determined by the UC-HPLC method was more than five times that determined by the enzymatic method (P < 0.05). Bisalbuminemia was found in 43 of 60 patients with obstructive jaundice accompanied by hypercholesterolemia. CONCLUSIONS: In patients with obstructive jaundice, the decreased (HDL-c + LDL-c)/TC ratio may be a novel marker to identify dyslipidemia secondary to LpX. The decreased ratio was associated with poor liver function and indicated disease progression.

Tailoring the Electronic Structure of Transition Metals by the V2C MXene Support: Excellent Oxygen Reduction Performance Triggered by Metal-Support Interactions.

The enhancement of oxygen reduction reaction (ORR) activity can significantly boost the performance of fuel cells. MXene-supported transition metals with strong metal-support interactions (SMSI) are an effective strategy to increase the catalytic activity and durability while decreasing the usage of noble metals. Herein, a series of composites of transition-metal atoms (Ni, Pd, Pt, Cu, Ag, and Au) deposited on V2C MXene are designed as potential catalysts for ORR using density functional theory. The calculation results demonstrate that all the transition metals prefer to form a monolayer on V2C (TMML/V2C) with high thermodynamic stability because of SMSI, in which the Pd, Pt, Ag, and Au monolayers exhibit high chemical stability during the ORR process. PtML/V2C exhibits the highest activity toward ORR with the overpotential down to 0.38 V and the largest energy barrier of 0.48 eV. The excellent catalytic performance originates from the modification of the electronic structure by the V2C support because of SMSI. Our studies elucidate the SMSI between transition-metal atoms and V2C MXene from the atomic level and thus rationally design the ORR catalyst at the cathode of fuel cells to enhance the activity while possessing high stability and less Pt usage.

Electrochemical Reduction of CO2 by SnOx Nanosheets Anchored on Multiwalled Carbon Nanotubes with Tunable Functional Groups.

Sn-based electrocatalysts are promising for the electrochemical CO2 reduction reaction (CO2RR), but suffer from poor activity and selectivity. A hierarchical structure composed of ultrathin SnOx nanosheets anchored on the surface of the commercial multiwalled carbon nanotubes (MWCNTs) is synthesized by a simple hydrothermal process. The electrocatalytic performance can be further tuned by functionalization of the MWCNTs with COOH, NH2 , and OH groups. Both SnOx @MWCNTs-COOH and SnOx @MWCNTs-NH2 show excellent catalytic activity for CO2 RR with nearly 100 % selectivity for C1 products (formate and CO). SnOx @MWCNTs-COOH has favorable formate selectivity with a remarkably high faradaic efficiency (FE) of 77 % at -1.25 V versus standard hydrogen electrode (SHE) and a low overpotential of 246 mV. However, SnOx @MWCNTs-NH2 manifests increased selectivity for CO with higher current density. Density functional theory calculations and experimental studies demonstrate that the interaction between Sn species and functional groups play an important role in the tuning of the catalytic activity and selectivity of these functionalized electrocatalysts. SnOx @MWCNTs-COOH and SnOx @MWCNTs-NH2 both effectively inhibit the hydrogen evolution reaction and prove stable without any significant degradation over 20 h of continuous electrolysis at -1.25 V versus SHE.

Density functional study on the high catalytic performance of single metal atoms on the NbC(001) surface.

The adsorption and activation of O2 is regarded as the first critical step for the oxygen reduction reaction (ORR), and catalysts with a high performance toward O2 adsorption and activation would provide a theoretical foundation for further investigations. Here, we have studied the adsorption and electronic properties as well as the catalytic activities of group 9-11 single metal atoms deposited on NbC(001), denoted M/NbC(001). According to the location of the d-band centers and the frontier molecular orbital analysis, single metals of Co, Rh, Ir and Ni on NbC(001) exhibit higher activities than other metals (Pd, Pt, Cu, Ag and Au). The quite different catalytic activities of M/NbC(001) may be attributed to the differences in their electro-negativities and work-functions. Meanwhile, the reasonable stabilities of Co, Rh, Ir and Ni on NbC(001) were clarified by investigating the agglomeration resistance and oxidation resistance, and the results indicate that Co and Ni have poor oxidative stability, and Rh and Ir are antioxidants on NbC(001). Further research into the adsorption and activation of O2 confirmed the outstanding properties of Rh/NbC(001) and Ir/NbC(001), which may provide great opportunities to find alternative catalysts.

The prevalence change of hyperlipidemia and hyperglycemia and the effectiveness of yearly physical examinations: an eight-year study in Southwest China.

BACKGROUND: The aim of this study was to investigate the prevalence changes of hyperlipidemia and hyperglycemia from 2009 to 2016 and the effectiveness of yearly physical examinations to hyperlipidemia and hyperglycemia prevention in Chengdu. METHODS: A total of 794 residents (499 males) who have undergone annual health check-ups for 8 consecutive years (from 2009 to 2016) in Chengdu, a city in southwest China were selected as the follow-up group, 7226 residents in 2009 and 75,068 residents in 2016 who underwent health examinations in the same hospital were chosen to be the contemporary control group. The concentration of fasting serum triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol (HDL-C) and glucose were measured and compared among these groups. RESULTS: There was a clear rise in the prevalence of hypercholesterolemia and hyperglycemia from 2009 to 2016 (p < 0.05). The follow-up group didn't show difference in levels of serum lipids and glucose compared with the general population after an 8-years' consecutive physical examination (p > 0.05), the follow-up cohort in the 8th year exhibited significant increases in serum total cholesterol and glucose compared with the 1st year (p < 0.05). CONCLUSION: The prevalence of hypercholesterolemia and hyperglycemia were increased significantly from 2009 to 2016. Annual physical examination didn't show a positive effect in the prevention of hypercholesterolemia and hyperglycemia. Health education should be improved to ensure the fulfillment of the preventive objective of yearly physical examination.

First-principles investigation of H2S adsorption and dissociation on titanium carbide surfaces.

The adsorption and dissociation reactions of H2S on TiC(001) are investigated using first-principles density functional theory calculations. The geometric and electronic structures of the adsorbed S-based species (including H2S, SH and S) on TiC(001) are analyzed in detail. It is found that the H2S is bound weakly, while SH and atomic S are bound strongly on the TiC(001) surface. The transition state calculations show that the formation of SH from H2S (H2S → SH + H) is very easy, while the presence of a co-adsorbed H will inhibit the further dissociation of SH (SH + H → S + H + H). In contrast, the hydrogenation of the adsorbed SH is rather easy (SH + H → H2S). Therefore, the dissociative SH can be removed via the hydrogenation reaction. It is concluded that it is difficult for H2S to dissociate completely to form atomic S and poison the TiC surface. The results will further provide understanding of the mechanism of the sulfur tolerance of the TiC anode of proton exchange membrane fuel cells (PEMFCs).

Density functional study on the resistance to sulfur poisoning of Ptx (x = 0, 1, 4 and 8) modified α-Mo2C(0001) surfaces.

The tolerance of sulfur poisoning of α-Mo2C(0001) surfaces with different Pt coverages is investigated combining the density functional theory (DFT) results with thermodynamics data using the ab initio atomistic thermodynamic method. It is found that on Mo2C(0001), Pt clusters tend to form two dimensional planar structures instead of aggregating. The clean Mo2C(0001) surface interacts with sulfides very strongly and is susceptible to sulfur poisoning. With increasing the coverage of Pt on the Mo2C surface, the interaction between sulfur and substrate is weakened. The sulfur tolerance ability increases in the order of Mo2C ≈ Pt1/Mo2C < Pt4/Mo2C < Pt8/Mo2C, where the coverage of Pt on the Mo2C plays a very effective role. The results provide theoretical guidance for designing Mo2C based catalysts with high activity and high sulfur resistance.

Imaging the halogen bond in self-assembled halogenbenzenes on silver.

Halogens are among the most electronegative elements, and the variations in size and polarizability of halogens require different descriptions of the intermolecular bonds they form. Here we use the inelastic tunneling probe (itProbe) to acquire real-space imaging of intermolecular-bonding structures in the two-dimensional self-assembly of halogenbenzene molecules on a metal surface. Direct visualization is obtained for the intermolecular attraction and the "windmill" pattern of bonding among the fully halogenated molecules. Our results provide a hitherto missing understanding of the nature of the halogen bond.