Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration.

Identifying molecular mediators of neural circuit development and/or function that contribute to circuit dysfunction when aberrantly reengaged in neurological disorders is of high importance. The role of the TWEAK/Fn14 pathway, which was recently reported to be a microglial/neuronal axis mediating synaptic refinement in experience-dependent visual development, has not been explored in synaptic function within the mature central nervous system. By combining electrophysiological and phosphoproteomic approaches, we show that TWEAK acutely dampens basal synaptic transmission and plasticity through neuronal Fn14 and impacts the phosphorylation state of pre- and postsynaptic proteins in adult mouse hippocampal slices. Importantly, this is relevant in two models featuring synaptic deficits. Blocking TWEAK/Fn14 signaling augments synaptic function in hippocampal slices from amyloid-beta-overexpressing mice. After stroke, genetic or pharmacological inhibition of TWEAK/Fn14 signaling augments basal synaptic transmission and normalizes plasticity. Our data support a glial/neuronal axis that critically modifies synaptic physiology and pathophysiology in different contexts in the mature brain and may be a therapeutic target for improving neurophysiological outcomes.

High Stretch Associated with Mechanical Ventilation Promotes Piezo1-Mediated Migration of Airway Smooth Muscle Cells.

Ventilator-induced lung injury (VILI) during mechanical ventilation (MV) has been attributed to airway remodeling involving increased airway smooth muscle cells (ASMCs), but the underlying mechanism is not fully understood. Thus, we aimed to investigate whether MV-associated high stretch (>10% strain) could modulate mechanosensitive Piezo1 expression and thereby alter cell migration of ASMCs as a potential pathway to increased ASMCs in VILI. C57BL/6 mice and ASMCs were subjected to MV at high tidal volume (VT, 18 mL/kg, 3 h) and high stretch (13% strain, 0.5 Hz, 72 h), respectively. Subsequently, the mice or cells were evaluated for Piezo1 and integrin mRNA expression by immunohistochemical staining and quantitative PCR (qPCR), and cell migration and adhesion by transwell and cell adhesion assays. Cells were either treated or not with Piezo1 siRNA, Piezo1-eGFP, Piezo1 knockin, Y27632, or blebbistatin to regulate Piezo1 mRNA expression or inhibit Rho-associated kinase (ROCK) signaling prior to migration or adhesion assessment. We found that expression of Piezo1 in in situ lung tissue, mRNA expression of Piezo1 and integrin αVß1 and cell adhesion of ASMCs isolated from mice with MV were all reduced but the cell migration of primary ASMCs (pASMCs) isolated from mice with MV was greatly enhanced. Similarly, cell line mouse ASMCs (mASMCs) cultured in vitro with high stretch showed that mRNA expression of Piezo1 and integrin αVß1 and cell adhesion were all reduced but cell migration was greatly enhanced. Interestingly, such effects of MV or high stretch on ASMCs could be either induced or abolished/reversed by down/up-regulation of Piezo1 mRNA expression and inhibition of ROCK signaling. High stretch associated with MV appears to be a mechanical modulator of Piezo1 mRNA expression and can, thus, promote cell migration of ASMCs during therapeutic MV. This may be a novel mechanism of detrimental airway remodeling associated with MV, and, therefore, a potential intervention target to treat VILI.

Sulfonyl Molecules Induced Oriented Lithium Deposition for Long-Term Lithium Metal Batteries.

Dendrites growth and unstable interfacial Li+ transport hinder the practical application of lithium metal batteries (LMBs). Herein, we report an active layer of 2,4,6-trihydroxy benzene sulfonyl fluorine on copper substrate that induces oriented Li+ deposition and generates highly crystalline solid-electrolyte interphase (SEI) to achieve high-performance LMBs. The lithiophilic -SO2 - groups of highly crystalline SEI accept the rapidly transported Li+ ions and form a dense inner layer of LiF and Li3 N, which regulate Li+ plating morphology along the (110) crystal surface toward dendrite-free Li anode. Thus, Li||Cu cells with lithiophilic SEI achieve an average deposition efficiency of 99.8 % after 700 cycles, and Li||Li cells operate well for 1100 h. Besides, Li||LiNi0.8 Co0.1 Mn0.1 O2 cells with modified SEI exhibit a capacity retention that is 14 times than that of conventional SEI. Even at -60 °C, Li||Cu cells reach stable deposition efficiency of 83.2 % after 100 cycles.

Mechanistic Insight into Acceptorless Dehydrogenation of Methanol to Syngas Catalyzed by MACHO-Type Ruthenium and Manganese Complexes: A DFT Study.

The acceptorless dehydrogenation of methanol to produce carbon monoxide (CO) and dihydrogen (H2) mediated by MACHO-type 1-Ru and 1-Mn complexes was theoretically investigated via density functional theory calculations. The 1-Ru-catalyzed process involves the formation of active species 4-Ru through a methanol-bridged H2 release pathway. Methanol dehydrogenation by 4-Ru yields formaldehyde and 1-Ru, followed by H2 release to regenerate 4-Ru (rate-determining step, ΔG‡ = 32.5 kcal/mol). Formaldehyde further reacts with methanol via nucleophilic attack of the MeO- ligand in the Ru complex (ΔG‡ = 9.6 kcal/mol), which is more favorable than the traditional methanol-to-formaldehyde nucleophilic attack (ΔG‡ = 33.8 kcal/mol) due to the higher nucleophilicity of MeO-. CO is ultimately produced through the methyl formate decarbonylation reaction. Accelerated H2 release in the early reaction stage compared to CO results from the initial methanol dehydrogenation and condensation of formaldehyde with methanol. In contrast, CO generation occurs later via methyl formate decarbonylation. The 1-Mn-catalyzed reaction has reduced efficiency compared to 1-Ru for the higher Gibbs energy barrier (ΔG‡ = 34.1 kcal/mol) of the rate-determining step. Excess NaOtBu promotes the reaction of CO and methanol, forming methyl formate, significantly reducing the CO/H2 ratio as the catalyst amount decreases. These findings deepen our understanding of the methanol-to-syngas transformation and can drive progress in this field.

Colchicine Attenuates Microvascular Obstruction after Myocardial Ischemia-Reperfusion Injury by Inhibiting the Proliferation of Neutrophil in Bone Marrow.

PURPOSE: Complete and rapid recanalization of blood flow by percutaneous coronary intervention (PCI) is the most effective intervention for patients with ST-segment elevation myocardial infarction (STEMI). However, myocardial ischemia/reperfusion (I/R) injury leads to microvascular obstruction (MVO), limiting its efficacy. Colchicine can reduce myocardial I/R injury, but its effect on MVO is unclear. Hence, this study aimed to assess the role and mechanism of colchicine on MVO. METHODS: Clinical data on STEMI patients with PCI were collected and risk factors related to MVO were analyzed. The rat myocardial I/R model was established to evaluate the MVO by thioflavin S staining. The myocardial I/R model of mice was treated with PBS or colchicine at the reperfusion. The effect of colchicine on cardiomyocyte apoptosis after I/R was evaluated by TUNEL and expression of cleaved caspase-3. ROS levels were detected in H9c2 cells to evaluate the colchicine effect on myocardial oxidative stress. Moreover, the mechanism through which colchicine attenuated MVO was examined using flow cytometry, WB, ELISA, immunohistochemistry, bioinformatics analysis, and immunofluorescence. RESULTS: Multivariate analysis showed that elevated neutrophils were associated with extensive MVO. Colchicine could attenuate MVO and reduce neutrophil recruitment and NETs formation after myocardial I/R. In addition, colchicine inhibited cardiomyocyte apoptosis in vivo and ROS levels in vitro. Furthermore, colchicine inhibited neutrophil proliferation in the bone marrow (BM) by inhibiting the S100A8/A9 inflammatory signaling pathway. CONCLUSIONS: Colchicine attenuated MVO after myocardial I/R injury by inhibiting the proliferation of neutrophils in BM through the neutrophil-derived S100A8/A9 inflammatory signaling pathway.

The predictive value of relative wall thickness on the prognosis of the patients with ST-segment elevation myocardial infarction.

OBJECTIVE: The study aimed to evaluate the prognostic value of relative wall thickness (RWT) in the patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 866 patients with STEMI admitted in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from November 2010 to December 2018 were enrolled in the current study retrospectively. Three methods were used to calculate RWT: RWTPW, RWTIVS+PW and RWTIVS. The included patients were divided according to the median values of RWTPW, RWTIVS+PW, and RWTIVS, respectively. Survival analysis were performed with Kaplan-Meier plot and multivariate Cox proportional hazard model was established to evaluate the adjusted hazard ratio of the three kinds of RWT for all cause death, cardiac death and MACE (major adverse cardiac death). RESULTS: There was no significance for the survival analysis between the low and high groups of RWTPW, RWTIVS+PW and RWTIVS at 30 days and 12 months. Nonetheless, the cumulative incidence of all cause death and cardiac death in the low group of RWTPW and RWTIVS+PW was higher than those in the high group at 60 months. The cumulative incidence of MACE in the low group of RWTPW was higher than the high group at 60 months. Multivariate Cox regression model showed that RWTPW were inversely associated with long-term cardiac death and MACE in STEMI patients. In the subgroup analysis, three calculations of RWT had no predictive value for the patients with anterior myocardial infarction. By contrast, RWTPW was the most stable independent predictor for the long-term outcomes of the patients with non-anterior myocardial infarction. CONCLUSION: RWTPW, RWTIVS+PW and RWTIVS had no predictive value for the long-term clinical outcomes of patients with anterior myocardial infarction, whereas RWTPW was a reliable predictor for all cause death, cardiac death and MACE in patients with non-anterior myocardial infarction.

Refractory ventricular tachycardia and heart failure due to anti-mitochondrial antibody-positive inflammatory myopathy.

BACKGROUND: Anti-mitochondrial antibody (AMA)-positive inflammatory myopathy, a rare type of idiopathic inflammatory myopathy which was frequently difficult to diagnose, can affect muscles and the structure and electrical conduction of the heart. Early identification and treatment of this myopathy can prevent serious cardiovascular adverse events and improve cardiac function. CASE PRESENTATION: We report a patient who experienced repeated syncope, ventricular tachycardia (VT) and heart failure accompanied by weakness and muscle atrophy. He was initially diagnosed with dilated cardiomyopathy and received implantable cardioverter-defibrillator therapy. He was subsequently misdiagnosed as muscular dystrophy due to progressive muscular atrophy. However, the patient developed repeated and refractory VT storms that were not alleviated by conventional therapy. Finally, he was diagnosed with AMA-positive inflammatory myopathy with cardiac injuries. The patient was markedly recovered by being treated with immunosuppressive and immunomodulatory therapy. CONCLUSION: AMA could be screened when discovering myopathies accompanied by unexplained cardiac symptoms. Our findings provide insights into the diagnosis and therapy of this rare and severe disease.

Chemical Activation of Piezo1 Alters Biomechanical Behaviors toward Relaxation of Cultured Airway Smooth Muscle Cells.

Inspired by the well-known phenomenon of stretch-induced airway dilation in normal lungs and the emerging stretch-responsive Piezo1 channels that can be chemically activated by specific agonists such as Yoda1, we attempted to investigate whether chemical activation of Piezo1 by Yoda1 can modulate the biomechanical behaviors of airway smooth muscle cells (ASMCs) so that it may be exploited as a novel approach for bronchodilation. Thus, we treated in vitro cultured rat ASMCs with Yoda1, and examined the cells for calcium signaling, cell stiffness, traction force, cell migration, and the mRNA expression and distribution of molecules relevant to cell biomechanics. The data show that ASMCs expressed abundant mRNA of Piezo1. ASMCs exposed to 1 µM Yoda1 exhibited a potent but transient Ca2+ signaling, and treatment with 1 µM Yoda1 for 24 h led to decreased cell stiffness and traction force, all of which were partially reversed by Piezo1 inhibitor GsMTx4 and Piezo1 knockdown, respectively. In addition, ASMCs treated with 1 µM Yoda1 for 24 h exhibited impaired horizontal but enhanced vertical cell migration, as well as significant changes in key components of cells' contractile machinery including the structure and distribution of stress fibers and alpha-smooth muscle actin (α-SMA) fibrils, the mRNA expression of molecules associated with cell biomechanics. These results provide the first evidence that chemical activation of Piezo1 by Yoda1 resulted in marked pro-relaxation alterations of biomechanical behaviors and contractile machinery of the ASMCs. These findings suggest that Piezo1-specific agonists may indeed have great potential as alternative drug agents for relaxing ASMCs.

Quality of life in patients with cervical cancer between the Han nationality and ethnic minorities in the Yunnan Province of China.

BACKGROUND: Cervical cancer is the fourth most diagnosed cancer and the leading cause of cancer death, and it still poses a crippling threat to women's health. China launched the National Cervical Cancer Screening Program for Rural Women in 2009, and an increasing number of cervical cancer patients have been detected. Health-related quality of life is not only the end point of cancer research but is also related to socioeconomic and clinical factors and has received an increasing amount of attention. In light of the characteristics of the Yunnan nationality, we conducted cross-sectional research to assess and explore the health-related quality of life in both Han and ethnic minority patients. METHODS: A cross-sectional study was conducted from January 2020 to May 2021 at the Third Affiliated Hospital of Kunming University/Yunnan Cancer Hospital. Patients, including 100 Han patients and 100 ethnic minorities, were interviewed using the FACT-Cx questionnaire within 3 months of receiving treatment. RESULTS: Patients of Han ethnicity and ethnic minorities were comparable in both sociodemographic and clinical features. The total FACT-Cx scores were 139.38 ± 9.83 and 134.39 ± 13.63 in Han and ethnic minority patients, respectively (P < 0.05). Significant differences were shown in physical well-being, emotional well-being and the FACT-Cx subscale between the Han and ethnic minority groups. Independent predictors of the FACT-Cx scale were ethnicity, educational level, participation in the National Cervical Cancer Screening Program for Rural Areas (NCCSPRA) and clinical stage. CONCLUSIONS: The results of our study imply that the HRQOL of Han patients is better than that of ethnic minority patients. Thus, clinicians and related health workers should pay more attention to the HRQOL of cervical cancer patients, especially for ethnic minority patients, and provide psychosocial interventions as much as possible to improve their HRQOL. Policies should also aim to strengthen health education regarding cervical cancer and expand the coverage of the NCCSPRA among those who are ethnic minorities, are older and have low educational levels.

Mechanical Ventilation-Related High Stretch Mainly Induces Endoplasmic Reticulum Stress and Thus Mediates Inflammation Response in Cultured Human Primary Airway Smooth Muscle Cells.

Ventilator-induced lung injury (VILI) occurs in mechanically ventilated patients of respiratory disease and is typically characterized by airway inflammation. However, recent studies increasingly indicate that a major cause of VILI may be the excessive mechanical loading such as high stretch (>10% strain) on airway smooth muscle cells (ASMCs) due to mechanical ventilation (MV). Although ASMCs are the primary mechanosensitive cells in airways and contribute to various airway inflammation diseases, it is still unclear how they respond to high stretch and what mediates such a response. Therefore, we used whole genome-wide mRNA-sequencing (mRNA-Seq), bioinformatics, and functional identification to systematically analyze the mRNA expression profiles and signaling pathway enrichment of cultured human ASMCs exposed to high stretch (13% strain), aiming to screen the susceptible signaling pathway through which cells respond to high stretch. The data revealed that in response to high stretch, 111 mRNAs with count ≥100 in ASMCs were significantly differentially expressed (defined as DE-mRNAs). These DE-mRNAs are mainly enriched in endoplasmic reticulum (ER) stress-related signaling pathways. ER stress inhibitor (TUDCA) abolished high-stretch-enhanced mRNA expression of genes associated with ER stress, downstream inflammation signaling, and major inflammatory cytokines. These results demonstrate in a data-driven approach that in ASMCs, high stretch mainly induced ER stress and activated ER stress-related signaling and downstream inflammation response. Therefore, it suggests that ER stress and related signaling pathways in ASMCs may be potential targets for timely diagnosis and intervention of MV-related pulmonary airway diseases such as VILI.

Prognostic value of triglyceride glucose (TyG) index in patients with acute decompensated heart failure.

BACKGROUND: The triglyceride glucose (TyG) index has been proposed as a reliable marker of insulin resistance (IR) and an independent predictor of cardiovascular disease risk. However, its prognostic value in patients with acute decompensated heart failure (ADHF) remains unclear. METHODS: A total of 932 hospitalized patients with ADHF from January 1st, 2018 to February 1st, 2021 were included in this retrospective study. The TyG index was calculated as ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. Patients were divided into tertiles according to TyG index values. The primary endpoints were all-cause death, cardiovascular (CV) death and major adverse cardiac and cerebral events (MACCEs) during follow-up. We used multivariate adjusted Cox proportional hazard models and restricted cubic spline analysis to investigate the associations of the TyG index with primary endpoints. RESULTS: During a median follow-up time of 478 days, all-cause death, CV death and MACCEs occurred in 140 (15.0%), 103 (11.1%) and 443 (47.9%) cases, respectively. In multivariate Cox proportional hazard models, the risk of incident primary endpoints was associated with the highest TyG tertile. After adjustment for confounding factors, hazard ratios (HRs) for the highest tertile (TyG index ≥ 9.32) versus the lowest tertile (TyG index < 8.83) were 2.09 (95% confidence interval [CI], 1.23-3.55; p = 0.006) for all-cause death, 2.31 (95% CI, 1.26-4.24; p = 0.007) for CV death and 1.83 (95% CI, 1.18-3.01; p = 0.006) for MACCEs. Restricted cubic spline analysis also showed that the cumulative risk of primary endpoints increased as TyG index increased. When the TyG index was used as a continuous variable, the hazard ratios of the three primary endpoints rapidly increased within the higher range of the TyG index (all cause death, TyG > 9.08; CV death, TyG > 9.46; MACCEs, TyG > 9.87). CONCLUSIONS: The elevated TyG index was independently associated with poor prognosis, and thus would be useful in the risk stratification in patients with ADHF.

The association between fibrinogen-to-albumin ratio (FAR) and adverse prognosis in patients with acute decompensated heart failure at different glucose metabolic states.

BACKGROUND: Circulating fibrinogen-to-albumin ratio (FAR) has been proposed as a novel inflammatory biomarker and a cardiovascular disease risk predictor. However, its prognostic value in patients with acute decompensated heart failure (ADHF) and different glycemic metabolic states remains ambiguous. METHODS: A total of 1031 hospitalized patients with ADHF from January 2018 to May 2021 were included in the study. The primary endpoints were the major adverse cardiac and cerebral events (MACCEs). Patients were categorized into high-level FAR (FAR-H) and low-level FAR (FAR-L) groups based on the optimal cut-off value of FAR obtained from restricted cubic spline function analysis. The Kaplan-Meier plots and three multivariate-adjusted Cox proportional hazard models were used to determine the association between FAR and the risk of developing MACCEs in patients with ADHF at different glycemic metabolic states. RESULTS: MACCEs occurred in 483 (46.8%) patients during a median follow-up time of 520 days. The optimal FAR cut-off value was 0.079. Upon analyzing the Kaplan-Meier plots, the incidence of MACCEs was significantly different between the FAR groups in all patients and patients with diabetes mellitus (p < 0.05). After adjusting for the confounding factors, the hazard ratio (HR) for MACCEs in the FAR-H group was 1.29 compared with the FAR-L group in all patients (Model 3: 95% CI 1.07-1.56, p = 0.007). Additionally, high FAR was associated with MACCEs in three multivariate Cox models (Model 1, HR = 1.52, 95% CI 1.17-1.96, p = 0.002; Model 2, HR = 1.46, 95% CI 1.13-1.89, p = 0.004; Model 3, HR = 1.48, 95% CI 1.14-1.92, p = 0.003) in DM patients. But no significant differences were found between the FAR groups for prediabetes mellitus (Pre-DM) and normal glucose regulation (NGR) using the three Cox models (all p-values were > 0.05). CONCLUSIONS: Elevated FAR was independently associated with poor prognosis in patients with ADHF and DM and thus could be used as a risk stratification tool and a potential therapeutic target in the future.

Highly Conjugated Graphitic Carbon Nitride Nanofoam for Photocatalytic Hydrogen Evolution.

As a metal-free photocatalyst, graphitic carbon nitride (g-CN) shows great potential for photocatalytic water splitting, although its performance is significantly limited by structural defects due to incomplete polymerization. In the present work, we successfully synthesize highly conjugated g-CN nanofoam through an iodide substitution technique. The product possesses a high polymerization degree, low defect density, and large specific surface area; as a result, it achieves a hydrogen evolution rate of 9.06 mmol h-1 g-1 under visible light irradiation, with an apparent quantum efficiency (AQE) of 18.9% at 420 nm. Experimental analysis and theoretical calculations demonstrate that the recombination of photogenerated carriers at C-NHx defects was effectively depressed in the nanofoam, giving rise to the high photocatalytic activity.

Optimizing the Bacteriostatic and Cytocompatibility Properties of Poly(hexamethylene guanidine) Hydrochloride (PHMG) via the Guanidine/Alkane Ratio.

The emergence of "superbugs" is not only problematic and potentially lethal for infected subjects but also poses serious challenges for the healthcare system. Although existing antibacterial agents have been effective in some cases, the side effects and biocompatibility generally present difficulties. The development of new antibacterial agents is therefore urgently required. In this work, we have adapted a strategy for the improvement of poly(hexamethylene guanidine) hydrochloride (PHMG), a common antibacterial agent. This involves copolymerization of separate monomer units in varying ratios to find the optimum ratio of the hydrocarbon to guanidine units for antibacterial activity. A series of these copolymers, designated as PGB, was synthesized. By varying the guanidine/hydrophobic ratio and the copolymer molecular weight, a structure-optimized PGB was identified that showed broad-spectrum antibacterial activity and excellent biocompatibility in solution. In an antibacterial assay, the copolymer with the optimum composition (hydrophobic unit content 25%) inhibited >99% Staphylococcus aureus and was compatible with mammalian cells. A polyurethane emulsion containing this PGB component formed transparent, flexible films (PGB-PU films) on a wide range of substrate surfaces, including soft polymers and metals. The PGB-PU films showed excellent bacteriostatic efficiency against nosocomial drug-resistant bacteria, such as Pseudomonas aeruginosa and methicillin-resistant S. aureus (MRSA). It is concluded that our PGB polymers can be used as bacteriostatic agents generally and in particular for the design of antibacterial surfaces in medical devices.

Major vault protein attenuates cardiomyocyte injury in doxorubicin-induced cardiomyopathy through activating AKT.

BACKGROUND: Doxorubicin (DOX) has limited chemotherapy application for malignancies due to cardiotoxicity. The pathogenesis of DOX-induced cardiomyopathy (DiCM) is yet to be elucidated. Increasing studies proved that activation of AKT prevented cardiomyocyte apoptosis and cardiac dysfunction in response to DOX insult. Our previous studies indicated that major vault protein (MVP) deficiency was accompanied by suppressed phosphorylation of AKT in metabolic diseases. This study aimed to investigate the role and underlying mechanism of MVP on cardiomyocyte apoptosis in DiCM. METHODS: Mice were intraperitoneally injected with DOX 5 mg/kg, once a week for 5 weeks, the total cumulative dose was 25 mg/kg. Cardiomyocyte-specific MVP overexpression was achieved using an adeno-associated virus system under the cTnT promoter after the fourth DOX injection. Cardiac function was examined by echocardiography followed by euthanasia. Tissue and serum were collected for morphology analysis and biochemical examination. RESULTS: Herein, we found that MVP expression was upregulated in DOX-treated murine hearts. Cardiac-specific MVP overexpression alleviated DOX-induced cardiac dysfunction, oxidative stress and fibrosis. Mechanistically, MVP overexpression activated AKT signaling and decreased cardiomyocyte apoptosis in DiCM. CONCLUSIONS: Based on these findings, we supposed that MVP was a potential therapeutic agent against DiCM.

Proteomic Characterization of the Dynamics of Ischemic Stroke in Mice.

Novel therapies and biomarkers are needed for the treatment of acute ischemic stroke (AIS). This study aimed to provide comprehensive insights into the dynamic proteome changes and underlying molecular mechanisms post-ischemic stroke. TMT-coupled proteomic analysis was conducted on mouse brain cortex tissue from five time points up to 4 weeks poststroke in the distal hypoxic-middle cerebral artery occlusion (DH-MCAO) model. We found that nearly half of the detected proteome was altered following stroke, but only ∼8.6% of the changes were at relatively large scales. Clustering on the changed proteome defined four distinct expression patterns characterized by temporal and quantitative changes in innate and adaptive immune response pathways and cytoskeletal and neuronal remodeling. Further analysis on a subset of 309 "top hits", which temporally responded to stroke with relatively large and sustained changes, revealed that they were mostly secreted proteins, highly correlated to different cortical cytokines, and thereby potential pharmacodynamic biomarker candidates for inflammation-targeting therapies. Closer examination of the top enriched neurophysiologic pathways identified 57 proteins potentially associated with poststroke recovery. Altogether, our study generated a rich dataset with candidate proteins worthy of further validation as biomarkers and/or therapeutic targets for stroke. The proteomics data are available in the PRIDE Archive with identifier PXD025077.

Quasi-Isotropically Thermal Conductive, Highly Transparent, Insulating and Super-Flexible Polymer Films Achieved by Cross Linked 2D Hexagonal Boron Nitride Nanosheets.

Polymer-based thermal management materials (TIMs) show great potentials as TIMs due to their excellent properties, such as high insulation, easy processing, and good flexibility. However, the limited thermal conductivity seriously hinders their practical applications in high heat generation devices. Herein, highly transparent, insulating, and super-flexible cellulose reinforced polyvinyl alcohol/nylon12 modified hexagonal boron nitride nanosheet (PVA/(CNC/PA-BNNS)) films with quasi-isotropic thermal conductivity are successfully fabricated through a vacuum filtration and subsequent self-assembly process. A special structure composed of horizontal stacked hexagonal boron nitride nanosheets (h-BNNSs) connected by their warping edges in longitudinal direction, which is strengthened by cellulose nanocrystals, is formed in PVA matrix during self-assembly process. This special structure makes the PVA/(CNC/PA-BNNS) films show excellent thermal conductivity with an in-plane thermal conductivity of 14.21 W m-1 K-1 and a through-plane thermal conductivity of 7.29 W m-1 K-1 . Additionally, the thermal conductive anisotropic constants of the as-obtained PVA/(CNC/PA-BNNS) films are in the range of 1 to 4 when the h-BNNS contents change from 0 to 60 wt%, exhibiting quasi-isotropic thermal conductivity. More importantly, the PVA/(CNC/PA-BNNS) films exhibit excellent transparency, super flexibility, outstanding mechanical strength, and electric insulation, making them very promising as TIMs for highly efficient heat dissipation of diverse electronic devices.

Index of microcirculatory resistance predicts long term cardiac systolic function in patients with STEMI undergoing primary PCI.

BACKGROUND: To evaluate the predictive value of the index of microcirculatory resistance (IMR) for long-term cardiac systolic function after primary percutaneous coronary intervention (pPCI) in patients with acute anterior wall ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 53 acute anterior wall STEMI patients were included and followed up within 1-year. IMR was measured to evaluate the immediate intraoperative reperfusion. IMR > 40 U was defined as the high IMR group and ≤ 40 U was defined as the low IMR group. Left ventricular ejection fraction (LVEF) was measured by echocardiography at 24 h, 1 month, 3 months, and 1 year after PCI to analyze the correlation between IMR and cardiac systolic function. Heart failure was estimated according to classification within one year. RESULTS: The ratio of TMPG (TIMI myocardial perfusion grade) 3 (85.7% vs. 52%, p = 0.015) and STR (ST-segment resolution) > 70% (82.1% vs. 48%, p = 0.019) were significantly higher in the low IMR group. The LVEF in the low IMR group was significantly higher than that in the high IMR group at 3 months (43.06 ± 2.63% vs. 40.20 ± 2.67%, p < 0.001) and 1 year (44.16 ± 2.40% vs. 40.13 ± 3.48%, p < 0.001). IMR was negatively correlated with LVEF at 3 months (r = - 0.1014, p = 0.0040) and 1 year (r = - 0.1754, p < 0.0001). CONCLUSIONS: The IMR showed significant negative correlation with the LVEF value after primary PCI. The high IMR is a strong predictor of heart failure within 1 year after anterior myocardial infarction.

Healthy-related quality of life in patients with cervical cancer in Southwest China: a cross-sectional study.

BACKGROUND: Cervical cancer is the second most common female malignant tumor in the world. According to a study in 2018, the incidence of cervical cancer in Yunnan Province of China was 11.42 per 100,000, the mortality rate was 3.77 per 100,000, and higher than the national average. Health-related quality of life (HRQoL) can be used not only in the selection and effect evaluation of clinical treatment plans of cervical cancer, but also in the evaluation of prognosis and long-term survival status. In this study, 288 cervical cancer patients admitted to the Yunnan Cancer Hospital in Southwest China from 2018 to 2020 were used as the survey objects to understand the HRQoL of cervical cancer patients and explore the related factors that affect HRQoL. METHODS: The Chinese version of the functional assessment of cancer therapy-cervix (functional assessment of cancer therapy-cervix v4.0, FACT-Cx V4) was used to investigate 288 patients with cervical cancer in Yunnan Province. Statistical analysis was performed using t-test, analysis of variance, multiple linear regression and other methods. RESULTS: The total FACT-Cx score of cervical cancer patients was (130.16 ± 14.20), the physical well-being (PWB) score was (22.02 ± 4.47), the social/family well-being (SWB) score was (25.66 ± 3.59), the emotional well-being (EWB) score was (19.75 ± 3.54), the functional well-being (FWB) score was (16.91 ± 5.01) and the additional focus area (cervical cancer subscale, CxS) score was (45.78 ± 4.61). From the multi-factor analysis results, the scores of PWB, FWB, Cxs and the total FACT-Cx were related to the choice of different treatment methods, the PWB scores of patients with concurrent chemoradiotherapy was low(ß = - 1.67, P = 0.003), the FWB scores of patients with concurrent chemoradiotherapy was low(ß = - 2.02, P = 0.001), the CxS scores of patients with concurrent chemoradiotherapy was low(ß = - 1.61, P = 0.006), the total score of FACT-Cx of patients with concurrent chemoradiotherapy was low(ß = - 5.91, P = 0.001). SWB score was affected by marital status, married patients had high PWB scores(ß = 5.44, P = 0.006). The patients with heavy disease expenditures as aproportion of family disposable income(ß = - 3.82, P = 0.002) and aged 60 and above(ß = - 3.29, P = 0.003) had lower FWB scores. The total score FACT-Cx of patients participating in cervical cancer screening was higher(ß = 7.61, P = 0.001). CONCLUSION: The choice of treatment method is the common influencing factor of PWB, FWB, Cxs and the total FACT-Cx. Disease expenditures as a proportion of family disposable income, the treatment method, the marital status and whether to participate in cervical cancer screening affect the patient's evaluation of their own HRQoL. Medical staff should pay special attention to the choice of different treatment methods, popularize vaccination knowledge and cervical cancer screening, give more humanistic care and health education to cervical cancer patients who have low education level, poor economic conditions, divorced or separated, and encourage patients to participate in active treatment to improve the health-related quality of life.

Comparison of the prognosis for different onset stage of cardiogenic shock secondary to ST-segment elevation myocardial infarction.

OBJECTIVES: The study was conducted to evaluate the outcomes of different onset stage of cardiogenic shock (CS) in the patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Total 675 STEMI patients who had undergone primary percutaneous coronary intervention (pPCI) from November 2010 to December 2017 in Nanjing Drum Tower Hospital were enrolled. According to the onset time of CS, the cohort was divided into three groups: Non-CS group, CS on admission group and Developed CS group. The short-term (30 days), middle-term (12 months) and long-term (80 months) outcomes were analyzed. COX proportional hazard models were established for identification of the predictors. RESULTS: The all cause death, cardiac death and major adverse cardiac events (MACE) at 30 days were similar among the three groups. The incidence of MACE in the CS on admission group was significantly higher than the other two groups at 12 months. As to the long-term outcomes, the CS on admission group had lower survival rate than the other two groups. The Develop CS group had lower survival rate than Non-CS group numerically with a trend towards statistical significance. The incidence of cardiac death in the Non-CS group was the lowest. The incidence of MACE in the CS on admission group was much higher compared with the other two groups. After multivariate analysis, the independent predictors of all cause death included age, male sex, prior stroke and LVEF. The independent predictors of cardiac death included age, male sex, prior stroke, LVEF, CS on admission and developed CS. The independent predictors of MACE included age, prior stroke, LVEF, multivessel lesions, post-PCI TIMI grade 1 and CS on admission. CONCLUSIONS: The long-term outcomes of CS on admission group were the worst of all. The outcomes of Developed CS group laid between the other two groups. The consequences highlighted the importance of prevention for CS developing in the STEMI patients during hospitalization.