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While many drugs are effective at reducing the relapse frequency of multiple sclerosis (MS), there is an unmet need for treatments that slow neurodegeneration resulting from secondary disease progression. The mechanism of neurodegeneration in MS has not yet been established. Here, we discovered a potential pathogenetic role of ferroptosis, an iron-dependent regulated cell death mechanism, in MS. We found that critical ferroptosis proteins (acyl-CoA synthetase long-chain family member 4, ACSL4) were altered in an existing genomic database of MS patients, and biochemical features of ferroptosis, including lipid reactive oxygen species (ROS) accumulation and mitochondrial shrinkage, were observed in the experimental autoimmune encephalitis (EAE) mouse model. Targeting ferroptosis with ferroptosis inhibitors or reducing ACSL4 expression improved the behavioral phenotypes of EAE mice, reduced neuroinflammation, and prevented neuronal death. We found that ferroptosis was an early event in EAE, which may promote T-cell activation through T-cell receptor (TCR) signaling in vitro and in vivo. These data indicate that ferroptosis may be a potential target for treating MS.

BACKGROUND: Exercise training after lumbar fusion surgery (LFS) is important for regaining the strength in the spinal muscles, pain management, and minimizing dysfunction. It may be prudent to evaluate technologies such as web-based chat and social media apps for increasing the efficacy of post-surgery interventions in LFS patients. OBJECTIVE: To explore the effectiveness of a WeChat-based individualized post-discharge rehabilitation program in patients with LFS. METHODS: Seventy-two eligible discharged LFS patients were enrolled from October 2018 to February 2019. The experimental group (36 cases) received a 10-week WeChat-based individualized rehabilitation program, while the control group (36 cases) received routine follow-up guidance. The outcomes were measured using the Exercise Compliance Questionnaire, Numerical Rating Scale, Oswestry Disability Index and Chinese version of the self-efficacy for exercise scale. RESULTS: The analysis using generalized estimation equations method shows significant differences in the interaction effect of group*time in exercise compliance (Wald c2= 7.459, P< 0.05), group effect in pain (Wald c2= 5.811, P< 0.05) and self-efficacy (Wald c2= 16.383, P< 0.05). However, there was no significant difference between the experimental and control groups in the group effect in dysfunction improvement (Wald c2= 2.289, P> 0.05). CONCLUSIONS: The WeChat-based rehabilitation intervention can improve exercise compliance and self-efficacy, and help achieve greater pain relief compared to the routine intervention. However, the WeChat-based intervention did not offer better improvement in the self-dysfunction in the post-discharge LFS patients.

BackgroundCarotid body tumor surgery is associated with various complications. However, intraoperative cardiac arrest is very rare and no more than 10 cases have been reported.Case descriptionA 58-year-old woman diagnosed with bilateral carotid body tumors underwent right carotid body tumor surgery. Sudden cardiac arrest occurred during the resection and was attributed to carotid sinus hypersensitivity. The patient recovered after prompt treatment and the tumor was removed completely with no complications.ConclusionCardiac arrest attributed to carotid sinus hypersensitivity during carotid body tumor resection is very rare. Proper treatments can reverse intraoperative cardiac arrest. If carotid sinus hypersensitivity is detected preoperatively, prophylactic temporary pacemaker implantation may be appropriate.

Objectives To clarify the adaptability of cancer patients to return to work and explore its influencing factors. Design: A cross-sectional study Settings/participants: From March to October 2021, 283 cancer patients in the follow-up period were recruited from the oncology departments of four secondary and above hospitals and cancer friendship associations in Nantong city using self-developed scale of adaptability to return to work for cancer patients by convenience sampling method. Methods The contents included general sociodemographic data, disease-related data, cancer patients' readability to work Scale, Medical Coping Style Questionnaire, Social Support Rating Scale, Family Closeness and Readability Scale, General self-efficacy Scale and Social impact Scale. Paper questionnaires were used for face-to-face data collection, and SPSS17.0 was used for statistical analysis. Univariable analyses and multiple linear regression analysis were conducted. Results The overall score of cancer patients' adaptability to return to work was (87.05 ± 20.255), (22.54 ± 4.234) for the dimension of focused rehabilitation, (32.02 ± 9.013) for the dimension of reconstruction effectiveness, and (32.49 ± 9.023) for the dimension of adjustment planning. Multiple linear regression analysis showed that the current return to full-time work (β = 0.226, P 0.05), the current return to non-full-time work (β = 0.184, P 0.05), yield response (β = -0.132, P 0.05), and general self-efficacy (β = 0.226, P 0.05) could affect their return to work adaptation. Conclusion The results of status quo and influencing factors showed that the adaptability of cancer patients to return to work was generally higher in this study. Patients who had returned to work, had lower yield coping score and higher general self-efficacy had better adaptability to return to work. Ethical approval It has been approved by the Human Research Ethics Committee of the Affiliated Hospital of Nantong University (Project No.202065)

Objective: To develop the Adaptability to Return-to-Work Scale (ARTWS) for cancer patients and evaluate its psychometric properties. Methods: In stage 1, the items of the initial scale were compiled based on the theoretical model, interview coding topics, and literature review results. Afterward, through two rounds of Delphi expert consultation and a pilot survey, the initial scale was further checked and revised. In stage 2, the psychometric properties of the ARTWS were assessed. Reliability was assessed by internal consistency and test-retest reliability evaluation. Exploratory Factor Analyses (EFA) and Confirmatory factor analysis (CFA) were performed to examine the construct validity. Moreover, the content validity was evaluated by the scale level content validity index (S-CVI). Results: The final ARTWS for cancer Patients consisted of 24 items. EFA extracted "Focusing on rehabilitation", "Rebuilding Self- efficiency", and "Adjusting plans" as common factors in determing adaptability of cancer patients to return-to-work, and the cumulative variance contribution rate for these three factors was 66.6%. The S-CVI of the total scale was 0.979. The Cronbach's α coefficient was 0.937. The 2-week test-retest reliability was 0.814. CFA showed that after model modification, the fitting of the model was within the acceptable range. Conclusion: The developed ARTWS for adult cancer patients has good reliability and validity, which can be used as a tool to measure the adaptability of cancer patients' return-to-work.

The present study aimed to explore the potential hub genes and pathways of ischaemic cardiomyopathy (ICM) and to investigate the possible associated mechanisms. Two microarray data sets ({"type":"entrez-geo","attrs":{"text":"GSE5406","term_id":"5406"}}GSE5406 and {"type":"entrez-geo","attrs":{"text":"GSE57338","term_id":"57338"}}GSE57338) were downloaded from the Gene Expression Omnibus (GEO) database. The limma package was used to analyse the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology (DO) and Gene Ontology (GO) annotation analyses were performed. A protein‐protein interaction (PPI) network was set up using Cytoscape software. Significant modules and hub genes were identified by the Molecular Complex Detection (MCODE) app. Then, further functional validation of hub genes in other microarrays and survival analysis were performed to judge the prognosis. A total of 1065 genes were matched, with an adjusted p 8 after MCODE analysis and MYH6 were ultimately identified. When validated in {"type":"entrez-geo","attrs":{"text":"GSE23561","term_id":"23561"}}GSE23561, MYH6 expression was lower in patients with CAD than in healthy controls (p

The spreading of misfolded alpha-synuclein (α-syn) protein has been observed in animal models of Parkinson's disease (PD) and other α-synucleinopathies that mimic human PD pathologies. In animal models, the spreading of α-syn has been associated with motor dysfunction and neuronal death. However, variability in both susceptible brain regions and cellular populations limits our understanding of the consequences of α-syn spreading and the development of associated therapies. Here, we have reviewed the physiological and pathological functions of α-syn and summarized the susceptible brain regions and cell types identified from human postmortem studies and exogenous α-syn injection-based animal models. We have reviewed the methods for inducing α-syn aggregation, the specific hosts, the inoculation sites, the routes of propagation, and other experimental settings that may affect the spreading pattern of α-syn, as reported in current studies. Understanding the spread of α-syn to produce a consistent PD animal model is vital for future drug discovery.

The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid-electrolyte interphase(SEI) growth would deteriorate its stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance.

Objective: With the increasing incidence and earlier onset of cancer, more and more cancer patients are facing the problems of return-to-work. This review is to explore the types, contents, and results of return-to-work interventions for cancer patients. Methods: This scoping review followed Arksey and O’Malley’s framework and PRISMA-ScR List. Three Chinese databases and five English databases were searched from the establishment of databases to 31 March, 2021. Article selection and data extraction were conducted by two researchers. Results: Thirty-two studies and 1916 cancer patients with mainly breast and gastrointestinal cancer were included. According to the contents, interventions could be divided into four types: (1) physical interventions ( n = 6), including high-intensity exercise, low-to-moderate intensity exercise, yoga, and upper limb functional training, (2) psychological interventions ( n = 2), including early active individualized psychosocial support and mindfulness-based recovery, (3) vocational interventions ( n = 14), including making work plans, educational leaflets, vocational consultations, electronic health intervention, and interventions targeting at employers, (4) multidisciplinary interventions ( n = 10), including any combination of above interventions. Physical exercises, making working plans, vocational consultations, educational leaflets, two combinations of vocational and physical interventions were validated to have positive results in enhancing cancer patients’ return-to-work. Conclusions: Return-to-work interventions for cancer patients are diversified and can be divided into physical, psychological, vocational, and multidisciplinary interventions. Medical staffs can utilize physical exercises, making working plans, vocational consultation, educational leaflets, combinations of vocational and physical interventions to enhance cancer patients’ return-to-work. Other interventions still need to be developed and validated.

Sodium ion batteries (SIBs) have recently been promising in the large-scale electric energy storage system, due to the low cost, abundant sodium resources. Mn-based layered oxide cathode materials have been widely investigated, because of the high theoretical specific capacity, low cost, and abundant reserves. However, their development is limited by the problems of Jahn-Teller distortion, Na

In this paper, to improve the situation of singleness of selecting results in hesitant fuzzy set decision-making and expand the range of choices for decision makers, we construct a hesitant fuzzy set clustering algorithm combined with fuzzy matroid operation. The algorithm synthesizes the r-cut set, fuzzy shrinking matroids in the fuzzy matroids and the operational properties of the fuzzy derived matroids, the r value also is used to connect the two types of fuzzy matroids to form a clustering algorithm. Finally, we apply the algorithm to the hesitant fuzzy set decision-making of job seekers choosing recruitment websites, each recruitment website as an optional scheme is divided into three categories of excellent to inferior schemes to provide job seekers with ideas and methods for favorably selecting recruitment websites.

Specific miRNA in immune thrombocytopenia (ITP) was screened to explore its intervention effects and mechanisms in ITP. MTT assay and CFSE staining were used to detect the effects of gradient concentrations of thrombopoietin (TPO) on cell proliferation. Expressions of differentially expressed miRNAs were analysed via qRT-PCR in TPO-induced megakaryocytes and ITP plasma. Effects of miR-557 on cell physiological functions were examined by MTT and flow cytometry. Expressions of miR-557, apoptosis-associated genes and Akt/ERK pathways were detected by qRT-PCR and Western blot as needed. Multinucleation of TPO-induced megakaryocytes was determined by megakaryocyte colonies. The toe skin and intestinal bleeding of the ITP rat model were observed and evaluated. Effects of miR-557 on the numbers of platelets, megakaryocytes, and peripheral blood platelets and the expressions of CD4(+) T cells, Treg cells, TGF-β, IL-6 and miR-557 in the ITP rats were detected by Giemsa staining, flow cytometry, ELISA and qRT-PCR. MiR-557 was identified as an specific miRNA associated with both ITP and TPO treatment. MiR-557 inhibitor enhanced the physiological functions of TPO-induced megakaryocytes, while miR-557 mimic had the opposite effect. At the molecular level, the expressions of miR-557, cleaved Caspase-3 and Bax were further silenced by inhibitor, on the contrary, the expressions of bcl-2, p-Akt and p-ERK were upregulated. Animal experiments showed that, miR-557 inhibitor increased the numbers of platelets and megakaryocytes, and improved the symptoms of ITP model rats. Our results indicated that miR-557 inhibitor improved ITP by regulating apoptosis-related genes and cellular immunity and activating the Akt/ERK pathway.

This study aimed to investigate the mechanism of type I interferon (IFN) in aggravating sepsis in bacterial infection, focusing on the roles of Caspase-11 (Casp11) and Gasdermin D (Gsdmd) in this process. Type I interferons, including IFNα and IFNβ, were used to treat peritoneal macrophage harvested from wild-type or IFNα/βR1 knockout (KO) mice, of which the levels of Casp11 and Gsdmd were monitored using real-time polymerase chain reaction (RT-PCR) and Western blot, the exposure to phosphatidylserine was monitored by flow cytometry, and tissue factor (TF) activation was assessed by RT-PCR and TF chromogenic assay. Endotoxemia in wild-type mice led to upregulation of Casp11 and Gsdmd in myeloid cells, which in contrast was attenuated in IFNα/βR1 KO mice. IFNα or IFNβ treatment led to dose-dependent upregulation of Casp11 and Gsdmd in peritoneal macrophages harvested from wild-type mice, but induced negligible changes in IFNα/βR1 KO mice. Type I IFN promoted phosphatidylserine exposure in peritoneal macrophage from wild-type mice but not IFNα/βR1 KO mice. Type I IFN induced insignificant changes of TF expression levels in both wild-type mice and IFNα/βR1 KO mice, but the TF activity was markedly increased in wild-type mice after type I IFN treatment. Our data suggested that the upregulation of Casp11 and Gsdmd in myeloid cells and macrophages induced by endotoxemia was reliant on the expression of IFNα/βR1. IFNα or IFNβ treatment efficiently upregulated Casp11 and Gsdmd, phosphatidylserine exposure, and TF activity of macrophages. Therefore, type I IFN could aggravate sepsis through upregulating Casp11 and Gsdmd.

The development of Na-ion full cells (NIFCs) suffers from the issue that the solid electrolyte interphase formation on the carbon anode consumes the limited sodium from cathode and thus incurs the decreased energy density and poor cyclic stability. To address these issues, we herein report that Na2O2 could be used as a sacrificial Na source through spraying its slurry on the surface of cathode, and investigate its stability as well as electrochemical behavior toward NIFCs. The results show that Na2O2 has good chemical and storage stability under a dry atmosphere and has no negative effect on the electrochemical performance of the cathode. Compared with the pristine cathode, the Na2O2-decorated cathode exhibits higher discharge capacity, superior capacity retention, and rate capability in a full cell with a carbon anode. Our cathode Na compensation strategy provides an effective avenue to make up for the irreversible Na+ loss cause by the formation of solid electrolyte interphase on the anode, thereby promoting the electrochemical performance and energy density of NIFCs toward the large-scale application.

Recycling of spent lithium-ion batteries has recently become a critical issue based on environmental concerns and a desire to reutilize resources. Among the existing recycling strategies, direct regeneration is largely encouraged from an economic and environmental perspective. However, current procedures used to separate the active cathode materials from the aluminum foil have some limitations for direct regeneration because they either destroy the structure of the cathode or use too many toxic and expensive reagents. Hence, we conducted comprehensive research on the microstructural evolution of the LiNi1−x−yCoxMnyO2 degraded electrode and then proposed a targeted method to recycle the spent cathode materials based on the increased residual lithium compounds. This separation process involves no other reagents but water, and toxic organic solvents, complicated processes, and waste treatments are unnecessary compared with the existing pretreatment strategies. Moreover, the separated cathodes are suitable for direct regeneration. Satisfactory capacity recovery of the cathode was achieved via simple sintering. Such a recycling process enables a sustainable closed-loop for the spent cathodes and provides new inspiration for the design of LIB recycling.

Sulfide-based solid-state electrolytes (SSEs) matched with alloy anodes are considered as promising candidates for application in all-solid-state batteries (ASSBs) to overcome the bottlenecks of the lithium (Li) anode. However, an understanding of the dynamic electrochemical processes on alloy anode in SSE is still elusive. Herein, in situ atomic force microscopy gives insights into the block-formation and stack-accumulation behaviors of Li precipitation on an Li electrode, uncovering the morphological evolution of nanoscale Li deposition/dissolution in ASSBs. Furthermore, two-dimensional Li-indium (In) alloy lamellae and the homogeneous solid electrolyte interphase (SEI) shell on the In electrode reveal the precipitation mechanism microscopically regulated by the alloy anode. The flexible and wrinkle-structure SEI shell further enables the electrode protection and inner Li accommodation upon cycles, elucidating the functional influences of SEI shell on the cycling behaviors. Such on-site tracking of the morphological evolution and dynamic mechanism provide an in-depth understanding and thus benefit the optimizations of alloy-based ASSBs.

With the ever increasing demand for low-cost and economic sustainable energy storage, Na-ion batteries have received much attention for the application on large-scale energy storage for electric grids because of the worldwide distribution and natural abundance of sodium element, low solvation energy of Na

Layered oxide cathodes usually exhibit high compositional diversity, thus providing controllable electrochemical performance for Na-ion batteries. These abundant components lead to complicated structural chemistry, closely affecting the stacking preference, phase transition and Na

Chemical modification of electrode materials by heteroatom dopants is crucial for improving storage performance in rechargeable batteries. Electron configurations of different dopants significantly influence the chemical interactions inbetween and the chemical bonding with the host material, yet the underlying mechanism remains unclear. We revealed competitive doping chemistry of Group IIIA elements (boron and aluminum) taking nickel-rich cathode materials as a model. A notable difference between the atomic radii of B and Al accounts for different spatial configurations of the hybridized orbital in bonding with lattice oxygen. Density functional theory calculations reveal, Al is preferentially bonded to oxygen and vice versa, and shows a much lower diffusion barrier than B

The present study explored the effects and its underlying mechanisms of four active fractions of Camellia nitidissima(leaf polyphenols, leaf saponins, flower polyphenols, and flower saponins in C. nitidissima) in inhibiting the proliferation and migration of non-small cell lung cancer(NSCLC) by suppressing the epidermal growth factor receptor(EGFR). MTT assay was used to detect the effect of four active fractions on the proliferation of NCI-H1975 and HCC827 cells. Wound healing assay and Transwell assay were adopted to evaluate the effect of four active fractions on the migration of NSCLC. The effect of four active fractions on the enzyme activity of EGFR was detected. Molecular docking was carried out to explore the direct action capacity and action sites between representative components of the four active fractions and EGPR. Western blot assay was employed to investigate the effect of four active fractions on the protein expression in EGFR downstream signaling pathways. The results of the MTT assay indicated that the cell viability of NCI-H1975 and HCC827 cells was significantly inhibited by four active fractions at 50, 100, 150, and 200 μg·mL~(-1) in a dose-dependent manner. Wound healing assay and Transwell assay revealed that the migration of NCI-H1975 and HCC827 cells was significantly suppressed by four active fractions. In addition, the results of the protein activity assay showed that the enzyme activity of EGFR was significantly inhibited by four active fractions. The molecular docking results confirmed that various components in four active fractions possessed strong binding activity to EGFR enzymes. Western blot assay revealed that four active fractions down-regulated the protein expression of EGFR and its downstream signaling pathways. It is concluded that the four active fractions of C. nitidissima can inhibit NSCLC. The mechanism may be related to EGFR and its downstream signaling pathways. This study provides a new scientific basis for the clinical treatment of NSCLC with active fractions of C. nitidissima, which is of reference significance for further research on the anti-tumor mechanism of C. nitidissima.

Na-ion cathode materials operating at high voltage with a stable cycling behavior are needed to develop future high-energy Na-ion cells. However, the irreversible oxygen redox reaction at the high-voltage region in sodium layered cathode materials generates structural instability and poor capacity retention upon cycling. Here, we report a doping strategy by incorporating light-weight boron into the cathode active material lattice to decrease the irreversible oxygen oxidation at high voltages (i.e., >4.0 V vs. Na+/Na). The presence of covalent B–O bonds and the negative charges of the oxygen atoms ensures a robust ligand framework for the NaLi1/9Ni2/9Fe2/9Mn4/9O2 cathode material while mitigating the excessive oxidation of oxygen for charge compensation and avoiding irreversible structural changes during cell operation. The B-doped cathode material promotes reversible transition metal redox reaction enabling a room-temperature capacity of 160.5 mAh g−1 at 25 mA g−1 and capacity retention of 82.8% after 200 cycles at 250 mA g−1. A 71.28 mAh single-coated lab-scale Na-ion pouch cell comprising a pre-sodiated hard carbon-based anode and B-doped cathode material is also reported as proof of concept., The irreversible oxygen redox reaction during charging to the high-voltage region causes cathode structural degradation and Na-ion cell capacity fading. Here, the authors report a B-doped cathode active material to mitigate the irreversible oxygen oxidation and increase the cell capacity.

Ischemic stroke represents a significant danger to human beings, especially the elderly. Interventions are only available to remove the clot, and the mechanism of neuronal death during ischemic stroke is still in debate. Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs. Here we report that the serine protease, thrombin, instigates ferroptotic signaling by promoting arachidonic acid mobilization and subsequent esterification by the ferroptotic gene, acyl-CoA synthetase long-chain family member 4 (ACSL4). An unbiased multi-omics approach identified thrombin and ACSL4 genes/proteins, and their pro-ferroptotic phosphatidylethanolamine lipid products, as prominently altered upon the middle cerebral artery occlusion in rodents. Genetically or pharmacologically inhibiting multiple points in this pathway attenuated outcomes of models of ischemia in vitro and in vivo. Therefore, the thrombin-ACSL4 axis may be a key therapeutic target to ameliorate ferroptotic neuronal injury during ischemic stroke.

Iron accumulation and α-synuclein aggregates (e.g., Lewy bodies) have been linked with the pathogenesis of Parkinson's disease (PD), with yet-to-be-determined interaction. Previous studies have indicated that iron binds to α-synuclein and triggers its aggregation in vitro, and iron is found enriched in Lewy bodies. In the current study, Joppe et al. have found that the propagation of pathological α-synuclein caused by intrastriatal α-synuclein preformed fibrils (PFFs) injection was unexpectedly attenuated in rodent brains in a model of brain iron elevation (neonatal iron feeding). PFFs stimulated microglial activation was also reduced in mice with elevated iron. These results may provide new insight into the complex interaction between these two key pathologies of PD.

Intensive understanding of the surface mechanism of cathode materials, such as structural evolution and chemical and mechanical stability upon charging/discharging, is crucial to design advanced solid-state lithium batteries (SSLBs) of tomorrow. Here, via

Multisource data, spatial density analysis, and a gravity model were used to evaluate and analyze differentiation and controls of human settlement locations in Jinan, China. The results indicate the following. (a) The spatial distribution of human settlements follows a block-style, is axially extended, and has a multicenter development pattern with a significant circular structure. (b) The distributions of many settlement types are similar to the total settlement distribution. Residential space exhibits the highest correlation with public space, whereas financial space has the smallest correlation with business space. A high matching value for human settlement is found at the junction of the five districts in Jinan, whereas the Pingyin and Shanghe counties exhibit the lowest value. (c) Areas with human settlement exhibit typical hierarchies. Performance is dominated by the five districts, Zhangqiu is subdominant, and other districts represent an edge-dependent hierarchical system. Radial spatial settlement structures are centered on the five districts, with a centripetal and multicentric “western dense, eastern sparse” regional pattern. (d) Topography is the main factor that generates differentiation. Road network density affects the distribution and grade of human settlement areas, gross domestic factor is a key factor that affects the formation of human settlement structures, and population aggregation is a prerequisite for human settlement distribution, as well as a catalytic factor for differentiation of human settlements.