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Electrochemically synthesizing NH3 via N2 is a facile and sustainable approach that involves multistep electron and proton transfer processes. Thus, consecutive electron and proton transfer is necessary. Here, a universal method with the assistance of magnetic stirring that can assemble Fe, Co, and Ni nanoparticles into nanochains is developed. Notably, the Fe nanochain, composed of amorphous Fe nanoparticles, facilitates electron and proton transfer, resulting in an enhanced NH3 yield (92.42 µg h-1 mg-1) and faradaic efficiency (20.02%) at -0.4 V vs. RHE during the electrochemical reduction of N2. This work offers new insight into designing tandem electrocatalysts.
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Protein phosphorylation is an important link in a variety of signaling pathways, and most of the important life processes in cells involve protein phosphorylation. Based on the amino acid residues of phosphorylated proteins, protein kinases can be categorized into the following families: serine/threonine protein kinases, tyrosine-specific protein kinases, histidine-specific protein kinases, tryptophan kinases, and aspartate/glutamyl protein kinases. Of all the protein kinases, most are serine/threonine kinases, where serine/threonine protein kinases are protein kinases that catalyze the phosphorylation of serine or threonine residues on target proteins using ATP as a phosphate donor. The current socially accepted classification of serine/threonine kinases is to divide them into seven major groups: protein kinase A, G, C (AGC), CMGC, Calmodulin-dependent protein kinase (CAMK), Casein kinase (CK1), STE, Tyrosine kinase (TKL) and others. After decades of research, a preliminary understanding of the specific classification and respective functions of serine/threonine kinases has entered a new period of exploration. In this paper, we review the literature of the previous years and introduce the specific signaling pathways and related therapeutic modalities played by each of the small protein kinases in the serine/threonine protein kinase family, respectively, in some common cardiovascular system diseases such as heart failure, myocardial infarction, ischemia-reperfusion injury, and diabetic cardiomyopathy. To a certain extent, the current research results, including molecular mechanisms and therapeutic methods, are fully summarized and a systematic report is made for the prevention and treatment of cardiovascular diseases in the future.
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Doenças Cardiovasculares , Proteínas Serina-Treonina Quinases , Humanos , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Animais , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Fosforilação , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologiaRESUMO
Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes.
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Doenças Cardiovasculares , Miócitos Cardíacos , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miócitos Cardíacos/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Animais , Apoptose/efeitos dos fármacos , Transdução de Sinais , Fármacos Cardiovasculares/uso terapêutico , Fármacos Cardiovasculares/farmacologiaRESUMO
Background and Objectives: Cardiac injury plays a critical role in contributing to the mortality associated with sepsis, a condition marked by various forms of programmed cell deaths. Previous studies hinted at the WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) involving in heart failure and endothelial injury. However, the precise implications of WWP2 in sepsis-induced cardiac injury, along with the underlying mechanisms, remain enigmatic. Methods: Sepsis induced cardiac injury were constructed by intraperitoneal injection of lipopolysaccharide. To discover the function of WWP2 during this process, we designed and performed loss/gain-of-function studies with cardiac-specific vectors and WWP2 knockout mice. Combination experiments were performed to investigate the relationship between WWP2 and downstream signaling in septic myocardium injury. Results: The protein level of WWP2 was downregulated in cardiomyocytes during sepsis. Cardiac-specific overexpression of WWP2 protected heart from sepsis induced mitochondrial oxidative stress, programmed cell death and cardiac injury, while knockdown or knockout of WWP2 exacerbated this process. The protective potency of WWP2 was predominantly linked to its ability to suppress cardiomyocyte ferroptosis rather than apoptosis. Mechanistically, our study revealed a direct interaction between WWP2 and acyl-CoA synthetase long-chain family member 4 (FACL4), through which WWP2 facilitated the ubiquitin-dependent degradation of FACL4. Notably, we observed a notable reduction in ferroptosis and cardiac injury within WWP2 knockout mice after FACL4 knockdown during sepsis. Conclusions: WWP2 assumes a critical role in safeguarding the heart against injury induced by sepsis via regulating FACL4 to inhibit LPS-induced cardiomyocytes ferroptosis.
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Previous studies have progressively elucidated the involvement of E3 ubiquitin (Ub) ligases in regulating lipid metabolism. Ubiquitination, facilitated by E3 Ub ligases, modifies critical enzymes in lipid metabolism, enabling them to respond to specific signals. In this review, we aim to present a comprehensive analysis of the role of E3 Ub ligases in lipid metabolism, which includes lipid synthesis and lipolysis, and their influence on cellular lipid homeostasis through the modulation of lipid uptake and efflux. Furthermore, it explores how the ubiquitination process governs the degradation or activation of pivotal enzymes, thereby regulating lipid metabolism at the transcriptional level. Perturbations in lipid metabolism have been implicated in various diseases, including hepatic lipid metabolism disorders, atherosclerosis, diabetes, and cancer. Therefore, this review focuses on the association between E3 Ub ligases and lipid metabolism in lipid-related diseases, highlighting enzymes critically involved in lipid synthesis and catabolism, transcriptional regulators, lipid uptake translocators, and transporters. Overall, this review aims to identify gaps in current knowledge, highlight areas requiring further research, offer potential targeted therapeutic approaches, and provide a comprehensive outlook on clinical conditions associated with lipid metabolic diseases.
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Transtornos do Metabolismo dos Lipídeos , Doenças Metabólicas , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Metabolismo dos Lipídeos , LipídeosRESUMO
Coat protein complex I (COPI) vesicles mediate the retrograde transfer of cargo between Golgi cisternae and from the Golgi to the endoplasmic reticulum (ER). However, their roles in the cell cycle and proliferation are unclear. This study shows that TANGO6 associates with COPI vesicles via two transmembrane domains. The TANGO6 N- and C-terminal cytoplasmic fragments capture RNA polymerase II subunit B (RPB) 2 in the cis-Golgi during the G1 phase. COPI-docked TANGO6 carries RPB2 to the ER and then to the nucleus. Functional disruption of TANGO6 hinders the nuclear entry of RPB2, which accumulates in the cytoplasm, causing cell cycle arrest in the G1 phase. The conditional depletion or overexpression of TANGO6 in mouse hematopoietic stem cells results in compromised or expanded hematopoiesis. Our study results demonstrate that COPI vesicle-associated TANGO6 plays a role in the regulation of cell cycle progression by directing the nuclear transfer of RPB2, making it a potential target for promoting or arresting cell expansion.
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Complexo I de Proteína do Envoltório , Retículo Endoplasmático , Complexo de Golgi , RNA Polimerase II , Animais , Camundongos , Transporte Ativo do Núcleo Celular , Proliferação de Células , Complexo I de Proteína do Envoltório/genética , Complexo I de Proteína do Envoltório/metabolismo , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , RNA Polimerase II/metabolismoRESUMO
High-sensitivity and fast-response photodetectors (PDs) are vital part of optical wireless communication (OWC) system. In this work, we develop an organic-inorganic hybrid perovskite material (MAPbI3) based p-i-n structured PD. By optimizing the precursor solution concertation, the PD showed a high responsivity of 0.98 A W-1, a fast response timetrise/tfallof 12/12.5 µs, a specific detectivity of 2.62 × 1013Jones, and the f-3dBof 24 kHz under the 532 nm laser and -0.2 V bias voltage. Furthermore, we designed an OWC system based on the prepared PD. With the baud rate of 19200 bps, the system exhibits a bit error rate less than 10-6, and it can realize 9.63 m long-distance communication and quick transmission applications such as strings, texts, photos, and audios. Our work demonstrates the great application potential of perovskite PDs in the field of optical communication.
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BACKGROUND: Cardiovascular disease (CVD) has been the leading cause of death worldwide for many years. In recent years, exosomes have gained extensive attention in the cardiovascular system due to their excellent biocompatibility. Studies have extensively researched miRNAs in exosomes and found that they play critical roles in various physiological and pathological processes in the cardiovascular system. These processes include promoting or inhibiting inflammatory responses, promoting angiogenesis, participating in cell proliferation and migration, and promoting pathological progression such as fibrosis. AIM OF REVIEW: This systematic review examines the role of exosomes in various cardiovascular diseases such as atherosclerosis, myocardial infarction, ischemia-reperfusion injury, heart failure and cardiomyopathy. It also presents the latest treatment and prevention methods utilizing exosomes. The study aims to provide new insights and approaches for preventing and treating cardiovascular diseases by exploring the relationship between exosomes and these conditions. Furthermore, the review emphasizes the potential clinical use of exosomes as biomarkers for diagnosing cardiovascular diseases. KEY SCIENTIFIC CONCEPTS OF REVIEW: Exosomes are nanoscale vesicles surrounded by lipid bilayers that are secreted by most cells in the body. They are heterogeneous, varying in size and composition, with a diameter typically ranging from 40 to 160 nm. Exosomes serve as a means of information communication between cells, carrying various biologically active substances, including lipids, proteins, and small RNAs such as miRNAs and lncRNAs. As a result, they participate in both physiological and pathological processes within the body.
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Cardiovascular disease (CVD) is a major threat to human health, accounting for 46% of non-communicable disease deaths. Glycolysis is a conserved and rigorous biological process that breaks down glucose into pyruvate, and its primary function is to provide the body with the energy and intermediate products needed for life activities. The non-glycolytic actions of enzymes associated with the glycolytic pathway have long been found to be associated with the development of CVD, typically exemplified by metabolic remodeling in heart failure, which is a condition in which the heart exhibits a rapid adaptive response to hypoxic and hypoxic conditions, occurring early in the course of heart failure. It is mainly characterized by a decrease in oxidative phosphorylation and a rise in the glycolytic pathway, and the rise in glycolysis is considered a hallmark of metabolic remodeling. In addition to this, the glycolytic metabolic pathway is the main source of energy for cardiomyocytes during ischemia-reperfusion. Not only that, the auxiliary pathways of glycolysis, such as the polyol pathway, hexosamine pathway, and pentose phosphate pathway, are also closely related to CVD. Therefore, targeting glycolysis is very attractive for therapeutic intervention in CVD. However, the relationship between glycolytic pathway and CVD is very complex, and some preclinical studies have confirmed that targeting glycolysis does have a certain degree of efficacy, but its specific role in the development of CVD has yet to be explored. This article aims to summarize the current knowledge regarding the glycolytic pathway and its key enzymes (including hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase-1 (PFK1), aldolase (Aldolase), phosphoglycerate metatase (PGAM), enolase (ENO) pyruvate kinase (PKM) lactate dehydrogenase (LDH)) for their role in cardiovascular diseases (e.g., heart failure, myocardial infarction, atherosclerosis) and possible emerging therapeutic targets.
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Doenças Cardiovasculares , Insuficiência Cardíaca , Humanos , Fosforilação Oxidativa , Aldeído Liases , Redes e Vias MetabólicasRESUMO
The manipulation of polarization states is crucial for tailoring light-matter interactions and has great applications in fundamental science. Nevertheless, conventional polarization measurement approaches are extremely challenging to determine the polarization state of incident terahertz (THz) beams. The combination of metasurfaces and inhomogeneous vector vortex beams (VVBs) provides a new solution for integrated polarization-related functional devices. Herein, a general design strategy for spin-multiplexing all-silicon metasurfaces is presented and demonstrated in THz polarization detection. The employment of basic building blocks with a high aspect ratio (AR) imparts a greater degree of freedom for generating vector beams, and those basic blocks are subsequently utilized to explore the visualized polarization state. With the assistance of a THz near-field scanning system, we evaluate the capability of reconstructing the incident polarization state from the longitudinal polarization component multiplexed by vortex beams with tight focusing characteristics. Not only that, we also utilize the polarization with dynamically varying behavior as the illumination method to elucidate the evolution trend of the polarization state under a single snapshot and establish a visualized parametric model. This work paves the way to realize ultra-compact THz polarization detection-related devices for future applications in remote sensing, high-resolution imaging, and communications.
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BACKGROUND: Cancer itself and surgery put a heavy burden on lung cancer patients, physiologically and psychologically. Enhancing self-efficacy during high-intensity interval training is essential for achieving the full benefit of pulmonary rehabilitation in lung cancer patients. OBJECTIVE: This study aimed to explore the effects of high-intensity interval training combined with team empowerment education on patients with lung resection. METHODS: This is a quasi-experimental trial with a pretest-posttest design. Participants were assigned to one of the 3 groups according to the order of admission: (1) combined intervention group, (2) intervention group, or (3) routine care group. The outcome measures included dyspnea, exercise capacity, exercise self-efficacy, anxiety, depression, postoperative indwelling time of thoracic drainage tube, and total in-hospital stay. RESULTS: Per-protocol results showed that dyspnea, exercise capacity, exercise self-efficacy, anxiety, and depression of the patients in the combined intervention group were significantly improved. However, no significant difference was observed in postoperative indwelling time of thoracic drainage tube or total in-hospital stay among the 3 groups. CONCLUSION: This hospital-based short-term high-intensity interval training combined with team empowerment education for lung cancer patients undergoing surgery was safe and feasible, indicating this program can be a promising strategy to manage perioperative symptoms. IMPLICATIONS FOR PRACTICE: This study provides evidence supporting preoperative high-intensity interval training as a promising method to make the best use of preoperative time, thus improving adverse symptoms in lung cancer patients undergoing surgery, and also provides a new strategy to raise exercise self-efficacy and promote patients' rehabilitation.
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Ferroptosis, a novel type of cell death mediated by the iron-dependent lipid peroxidation, contributes to the pathogenesis of the intervertebral disc degeneration (IDD). Increasing evidence demonstrated that melatonin (MLT) displayed the therapeutic potential to prevent the development of IDD. Current mechanistic study aims to explore whether the downregulation of ferroptosis contributes to the therapeutic capability of MLT in IDD. Current studies demonstrated that conditioned medium (CM) from the lipopolysaccharide (LPS)-stimulated macrophages caused a series of changes about IDD, including increased intracellular oxidative stress (increased reactive oxygen species and malondialdehyde levels, but decreased glutathione levels), upregulated expression of inflammation-associated factors (IL-1ß, COX-2 and iNOS), increased expression of key matrix catabolic molecules (MMP-13, ADAMTS4 and ADAMTS5), reduced the expression of major matrix anabolic molecules (COL2A1 and ACAN), and increased ferroptosis (downregulated GPX4 and SLC7A11 levels, but upregulated ACSL4 and LPCAT3 levels) in nucleus pulposus (NP) cells. MLT could alleviate CM-induced NP cell injury in a dose-dependent manner. Moreover, the data substantiated that intercellular iron overload was involved in CM-induced ferroptosis in NP cells, and MLT treatment alleviated intercellular iron overload and protected NP cells against ferroptosis, and those protective effects of MLT in NP cells further attenuated with erastin and enhanced with ferrostatin-1(Fer-1). This study demonstrated that CM from the LPS-stimulated RAW264.7 macrophages promoted the NP cell injury. MLT alleviated the CM-induced NP cell injury partly through inhibiting ferroptosis. The findings support the role of ferroptosis in the pathogenesis of IDD, and suggest that MLT may serve as a potential therapeutic approach for clinical treatment of IDD.
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Ferroptose , Degeneração do Disco Intervertebral , Sobrecarga de Ferro , Melatonina , Humanos , Melatonina/farmacologia , Degeneração do Disco Intervertebral/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Meios de Cultivo Condicionados/farmacologia , FerroRESUMO
The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD). RAW 264.7 Mφs were induced by lipopolysaccharide (LPS) to simulate Mφ polarization and the inflammatory reaction of Mφs with or without MLT were detected. Conditioned medium (CM) collected from these activated Mφs with or without MLT treatment were further used to incubate NP cells. The oxidative stress, inflammation and extracellular matrix (ECM) metabolism in NP cells were determined. Then, the changes in SIRT1/Notch signaling were detected. The agonist (SRT1720) and inhibitor (EX527) of SIRT1 were used to further explore the association among MLT. The interaction between SIRT1 and NICD was detected by immunoprecipitation (IP). Finally, puncture-induced rat IDD models were established and IDD degrees were clarified by X-ray, MRI, H&E staining and immunofluorescence (IF). The results of flow cytometry and inflammation detection indicated that LPS could induce M1-type Mφ polarization with pro-inflammatory properties. MLT significantly inhibited the aforementioned process and inhibited M1-type Mφ polarization, accompanied by the alleviation of inflammation. Compared with those without MLT, the levels of oxidative stress, pro-inflammatory cytokines and ECM catabolism in NP cells exposed to CM with MLT were markedly downregulated in a dose-dependent manner. The inhibition of SIRT1 and the enhancement of Notch were observed in activated Mφs and they can be reversed after MLT treatment. This prediction was further confirmed by using the SRT1720 and EX527 to activate or inhibit the signaling. The interaction between SIRT1 and NICD was verified by IP. In vivo study, the results of MRI, Pfirrmann grade scores and H&E staining demonstrated the degree of disc degeneration was significantly lower in the MLT-treated groups when compared with the IDD control group. The IF data showed M1-type Mφ polarization decreased after MLT treatment. MLT could inhibit M1-type Mφ polarization and ameliorate the NP cell injury caused by inflammation in vitro and vivo, which is of great significance for the remission of IDD. The SIRT1/Notch signaling pathway is a promising target for MLT to mediate Mφ polarization.
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AIM: To investigate the effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eight electronic databases including PubMed, Web of Science, Cochrane library, Embase, CINAHL, China National Knowledge Infrastructure, Wangfang and Weipu databases were systematically searched from inception of the database to January 10, 2022. METHODS: Statistical analysis was performed using Review Manager 5.4 and results were reported as mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CI). Outcomes were the forced expiratory volume in 1 second (FEV1), forced volume capacity (FVC) and percent of FEV1/FVC. The Cochrane Risk of Bias Tool was used to assess the risk of bias of included studies. The study protocol was not registered. RESULTS: Eight randomized controlled trials (RCTs) including 476 participants met the inclusion criteria and were included in meta-analysis. It was found that internet-based self-management interventions showed a significant improvement in FVC(L), while FEV1 (%), FEV1 (L), FEV1/FVC (%) and FVC (%) did not significantly improve. CONCLUSIONS: Internet-based self-management interventions were effective in improving pulmonary function in patients with COPD, caution should be exercised in interpreting the results. RCTs of higher quality are needed in the future to further demonstrate the effectiveness of the intervention. RELEVANCE TO CLINICAL PRACTICE: It provides evidence for internet-based self-management interventions in improving pulmonary function in patients with COPD. IMPACT: The results suggested that internet-based self-management interventions could improve the pulmonary function in people with COPD. This study provides a promising alternative method for patients with COPD who have difficulty seeking face-to-face self-management interventions, and the intervention can be applied in clinical settings. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.
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Doença Pulmonar Obstrutiva Crônica , Autogestão , Humanos , China , Internet , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , TelemedicinaRESUMO
Engineered cysteines are frequently used for site-specific conjugation in antibody-drug conjugate (ADC) development. When cysteine-engineered mAbs are produced in the cell culture process, the sulfhydryl groups on the engineered cysteines are mostly in an oxidized form. The oxidized cysteines require multiple steps (such as reduction, reoxidation, and buffer exchanges) to reactivate for bioconjugation, which complicates the ADC production process and reduces yields. In this study, we identified a Q166C mutation in the light chain that allows the presence of free sulfhydryl groups during cell culture and purification process. This mutation is in the constant region and away from sites involved in antigen binding or Fc-mediated functions. The free sulfhydryl reacts readily with maleimide in a mild solution at a high conjugation rate. This is only the second such site reported (the first one is Q124C in the light chain). Using the Q166C mutation, we conjugated an anti-angiopoietin-2 (Ang-2) peptide on bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, to construct a peptide antibody conjugate, Ava-Plus, which could block two pro-angiogenic factors simultaneously. Ava-Plus showed high affinity for both VEGF and Ang-2 and demonstrated higher activity than bevacizumab in inâ vitro cell migration and inâ vivo mouse xenograft models.
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Anticorpos Monoclonais , Imunoconjugados , Camundongos , Humanos , Animais , Anticorpos Monoclonais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Bevacizumab , Cisteína/genética , Compostos de Sulfidrila , Imunoconjugados/genéticaRESUMO
BACKGROUND: Hypertension can lead to podocyte damage and subsequent apoptosis, eventually resulting in glomerulosclerosis. Although alleviating podocyte apoptosis has clinical significance for the treatment of hypertensive nephropathy, an effective therapeutic target has not yet been identified. The function of septin4, a proapoptotic protein and an important marker of organ damage, is regulated by post-translational modification. However, the exact role of septin4 in regulating podocyte apoptosis and its connection to hypertensive renal damage remains unclear. METHODS: We investigated the function and mechanism of septin4 in hypertensive nephropathy to discover a theoretical basis for targeted treatment. Mouse models including Rosa 26 (Gt(ROSA)26Sor)-SIRT2 (silent mating type information regulation 2 homolog-2)-Flag-TG (transgenic) (SIRT2-TG) mice SIRT2-knockout, and septin4-K174Q mutant mice, combined with proteomic and acetyl proteomics analysis, followed by multiple molecular biological methodologies, were used to demonstrate mechanisms of SIRT2-mediated deacetylation of septin4-K174 in hypertensive nephropathy. RESULTS: Using transgenic septin4-K174Q mutant mice treated with the antioxidant Tempol, we found that hyperacetylation of the K174 site of septin4 exacerbates Ang II (angiotensin II)- induced hypertensive renal injury resulting from oxidative stress. Proteomics and Western blotting assays indicated that septin4-K174Q activates the cleaved-PARP1 (poly [ADP-ribose] polymerase family, member 1)-cleaved-caspase3 pathway. In septin4-knockdown human renal podocytes, septin4-K174R, which mimics deacetylation at K174, rescues podocyte apoptosis induced by Ang II. Immunoprecipitation and mass spectrometry analyses identified SIRT2 as a deacetylase that interacts with the septin4 GTPase domain and deacetylates septin4-K174. In Sirt2-deficient mice and SIRT2-knockdown renal podocytes, septin4-K174 remains hyperacetylated and exacerbates hypertensive renal injury. By contrast, in Rosa26-Sirt2-Flag (SIRT2-TG) mice and SIRT2-knockdown renal podocytes reexpressing wild-type SIRT2, septin4-K174 is hypoacetylated and mitigates hypertensive renal injury. CONCLUSIONS: Septin4, when activated through acetylation of K174 (K174Q), promotes hypertensive renal injury. Septin4-K174R, which mimics deacetylation by SIRT2, inhibits the cleaved-PARP1-cleaved-caspase3 pathway. Septin4-K174R acts as a renal protective factor, mitigating Ang II-induced hypertensive renal injury. These findings indicate that septin4-K174 is a potential therapeutic target for the treatment of hypertensive renal injury.
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Hipertensão Renal , Hipertensão , Animais , Humanos , Camundongos , Apoptose , Hipertensão Renal/genética , Rim/metabolismo , Camundongos Transgênicos , Proteômica , Sirtuína 2/genética , Sirtuína 2/metabolismoRESUMO
BACKGROUND: Cancer itself and surgery pose a heavy burden on adults with lung cancer. Yoga breathing exercises have been proposed as a form of pulmonary rehabilitation exercises to improve these patients' perioperative outcomes. OBJECTIVE: To investigate the impact of yoga breathing exercises based on a problem-solving model on dyspnea, exercise capacity, anxiety, depression, and postoperative indwelling time of thoracic drainage tube and compliance in adults with lung cancer undergoing surgery. METHODS: One hundred eight lung cancer patients were randomly assigned to receive problem-solving model-based yoga breathing exercises, yoga breathing exercises, or usual care. Outcomes were collected at admission, the day before surgery, and at discharge. RESULTS: Patients in the combined intervention group showed a significantly greater improvement in dyspnea, exercise capacity, and anxiety compared with the control group. Yoga breathing training can significantly improve patients' dyspnea and anxiety. Significant difference favoring the combined group was observed in exercise capability and compliance between the 2 intervention groups. However, there was no significant difference in depression or indwelling time of thoracic drainage tube among the 3 groups at any time point. CONCLUSION: Findings indicate that yoga breathing exercises are effective in alleviating perioperative symptoms of lung resection patients. Compared with yoga breathing exercises, applying additional problem-solving model may achieve a better effect. IMPLICATIONS FOR PRACTICE: Yoga breathing exercises can be considered as a promising pulmonary rehabilitation strategy for lung cancer patients with surgery. The problem-solving model could be integrated into yoga breathing exercises in clinical practice to enhance the rehabilitation effect.
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Climate change is a global concern. The goal of carbon neutrality and emission peak is a challenge for China and other developing countries. The carbon reduction policy for carbon neutrality and industrial transfer policy will be a research hotspot on carbon emissions. This study analyzed the spatial impact mechanism of industrial transfer on carbon emissions, especially the role of firm location decision and carbon reduction policy. Based on the dynamic deviation-share model, the industrial transfer products of 30 provinces in China during the "Twelfth Five-Year Plan" and "Thirteenth Five-Year Plan" periods were measured. The spatially weighted interaction model based on improved parameters was then utilized to explore the spatial effect of industrial transfer and carbon reduction policy on regional carbon emissions. The results show that the restrictive carbon reduction policy through centrifugal effect lead to the location shift of manufacturing firms. Industrial transfer and carbon emissions are significantly related. The restrictive carbon reduction policy has significant spatial emission reduction effect. The carbon reduction policy and industrial transfer level of different region comprehensively were the key factors affecting China's carbon neutral goal. The findings have implications for optimizing the scheme of carbon emission reduction tasks allocation between regions.
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Indústrias , Condições Sociais , Comércio , Carbono , China , Dióxido de Carbono , Desenvolvimento EconômicoRESUMO
BACKGROUND: Diffusion basis spectrum imaging (DBSI) is a noninvasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments. OBJECTIVE: To determine the utility of DBSI as a biomarker of CSM disease severity. METHODS: A single-center prospective cohort study enrolled 50 patients with CSM and 20 controls from 2018 to 2020. All patients underwent clinical evaluation and diffusion-weighted MRI, followed by diffusion tensor imaging and DBSI analyses. Diffusion-weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra-axonal changes by isotropic restricted and nonrestricted fraction. Including an intra-axonal diffusion compartment, DBSI improves estimations of axonal injury through intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using modified Japanese Orthopedic Association classifications. Imaging parameters were compared among patient groups using independent samples t tests and ANOVA. RESULTS: Twenty controls, 27 mild (modified Japanese Orthopedic Association 15-17), 12 moderate (12-14), and 11 severe (0-11) patients with CSM were enrolled. Diffusion tensor imaging and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and patients with CSM ( P < .05). DBSI fiber fraction, restricted fraction, and nonrestricted fraction were significantly different between groups ( P < .01). DBSI intra-axonal axial diffusivity was lower in mild compared with moderate (mean difference [95% CI]: 1.1 [0.3-2.1], P < .01) and severe (1.9 [1.3-2.4], P < .001) CSM. CONCLUSION: DBSI offers granular data on white matter tract integrity in CSM that provide novel insights into disease pathology, supporting its potential utility as a biomarker of CSM disease progression.
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Doenças da Medula Espinal , Espondilose , Humanos , Imagem de Tensor de Difusão/métodos , Espondilose/diagnóstico por imagem , Estudos Prospectivos , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/patologia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Imagem de Difusão por Ressonância Magnética , BiomarcadoresRESUMO
AIMS: This systematic review and meta-analysis aimed to evaluate the effects of home-based telehealth compared with usual care on six-minute walking distance (6MWD), health-related quality of life, anxiety and depression in patients with chronic obstructive pulmonary disease. METHODS: We identified randomized controlled trials through a systematic multidatabase search. Titles and abstracts were assessed for relevance. Two authors independently extracted data and assessed the risk of bias and quality of evidence. Meta-analyses were conducted using Review Manager and Stata. RESULTS: We included 32 randomized controlled trials (n = 5232). Devices used for home-based telehealth interventions included telephones, videos, and combined devices. The quality of the evidence was downgraded due to high risk of bias, imprecision, and inconsistency. Home-based telehealth significantly increased 6MWD by 35 m (SD = 30.42) and reduced symptom burden by 3 points (SD = -2.30) on the COPD assessment test compared with usual care. However, no significant differences in anxiety and depression were noted between the home-based telehealth group and the standard care group. In subgroup analysis, home-based telehealth significantly improved 6MWD and health status after 6-12 months and >12 months. CONCLUSION: Low quality evidence showed that home-based telehealth interventions reduce symptom burden and increase walking distance to a clinically meaningful extent in patients with COPD. However, no effects on depression and anxiety were observed.