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Objective: The purpose of this review was to examine the association between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and mortality rates in patients with acute pulmonary embolism (PE). Methods: PubMed Central, Scopus, Web of Science, and Embase were searched for studies reporting the association between NLR and PLR with mortality up to March 17th 2023. Adjusted ratios were sourced from studies and combined to generate pooled outcomes as odds ratio (OR) in a random-effects model. Risk of bias was assessed using the Newcastle Ottawa Scale. Results: Fifteen studies were included. Meta-analysis showed that NLR was a significant predictor of mortality in patients with PE (OR: 1.42 95% CI: 1.26, 1.61 I2=92%). Results were unchanged on sensitivity analysis and subgroup analysis based on study location, method of diagnosis, sample size, overall mortality rates, cut-offs, and follow-up. Pooled analysis failed to demonstrate PLR as a predictor of mortality in patients with PE (OR: 1.00 95% CI: 1.00, 1.01 I2=57%). Results were unchanged on sensitivity analysis and subgroup analysis based on study location, diagnosis of PE, overall mortality rates, and cut-off. Conclusion: Current evidence from retrospective studies shows that NLR can independently predict mortality in acute PE. Data on PLR was limited and failed to indicate an independent role in the prognosis of PE patients. Registration No. PROSPERO (CRD42023407573).
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OBJECTIVE: To investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters. METHODS: The remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated. RESULTS: The r2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1ß and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05). CONCLUSION: There are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches.
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A new naphthalene diimides extended-pillar[6]arene 1 with a large cavity and rich host-guest complexation properties was synthesized in high yield. It can not only form 1:2 complexes with large size polycyclic aromatic hydrocarbons but also form 1:1:1 ternary complex with perylene and 2,7-diazapyrenium. Moreover, the supramolecular exchange reaction from a 1:2 host-guest complex 1â¢(G3)2 formed by 1 and perylene to a 1:1:1 ternary complex 1â¢G3â¢G5 formed by 1 with perylene and 2,7-diazapyrenium salt was also investigated by 1H NMR experiments as well as theoretically calculations.
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Anode-free lithium (Li) metal batteries are promising alternatives to current Li-ion batteries due to their advantages such as high energy density, low cost, and convenient production. However, the copper (Cu) current collector accounts for more than 25 wt% of the total weight of the anode-free battery without capacity contribution, which severely reduces the energy and power densities. Here, a new family of ultralight composite current collectors with a low areal density of 0.78 mg cm-2, representing significant weight reduction of 49%-91% compared with the Cu-based current collectors for high-energy Li batteries, is presented. Rational molecular engineering of the polyacylsemicarbazide substrate enables enhanced interfacial interaction with the sputtered Cu layer, which results in excellent interfacial stability, flexibility, and safety for the obtained anode-free batteries. The battery-level energy density has been significantly improved by 36%-61%, and a maximum rate capability reaches 5 C (10 mA cm-2) attributed to the homogeneous Li+ flux and smooth Li deposition on the nanostructured Cu layer. The results not only open a new avenue to improve the energy and power densities of anode-free batteries via composite current collector innovation but, in a broader context, provide a new paradigm to pursue high-performance, high-safety, and flexible batteries.
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Carbonyl compounds are important components of natural organic matter (NOM) with high reactivity, so that play a pivotal role in the dynamic transformation of NOM. However, due to the lack of effective analytical methods, our understanding on the molecular composition of these carbonyl compounds is still limited. Here, we developed a high-throughput screening method to detect carbonyl molecules in complex NOM samples by combining chemical derivatization with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR-MS). In six different types of dissolved organic matter (DOM) samples tested in this study, 20-30 % of detected molecules contained at least one carbonyl group, with relative abundance accounted for 45-70 %. These carbonyl molecules displayed lower unsaturation level, lower molecular weight, and higher oxidation degree compared to non-carbonyl molecules. More importantly, the measured abundances of carbonyl molecules were consistent with the results of 13C nuclear magnetic resonance (NMR) analysis. Based on this method, we found that carbonyl molecules can be produced at DOM-ferrihydrite interface, thus playing a role in shaping the molecular diversity of DOM. This method has broad application prospects in screening carbonyl compounds from complex mixtures, and the same strategy can be used to directional identification of molecules with other functional groups as well.
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Compuestos Orgánicos , Compuestos Orgánicos/química , Espectrometría de Masas/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , Sustancias Húmicas/análisisRESUMEN
BACKGROUND: Craving is a core feature of addiction. Rumination and depression play a crucial role in the process of methamphetamine addiction. The aim of this study was to examine the relationship between rumination, depression and craving in methamphetamine patients, which has not been explored yet. METHODS: A total of 778 patients with methamphetamine user disorder (MUD) at the Xinhua Drug Rehabilitation Center, located in Mianyang City, Sichuan Province, China. We used a set of self-administered questionnaires that included socio-demographic, detailed drug use history, rumination, depression and craving information. The Rumination Response Scale (RRS) was used to measure rumination, the Beck Depression Inventory (BDI) to measure depression and the Visual Analogue Scale (VAS) to measure craving. RESULTS: There was a significant positive correlation between rumination and craving, or depression, and between depression and craving. Furthermore, depression mediated between rumination and craving, with a mediation effect of 160%. CONCLUSIONS: Our findings suggest that there is a close interrelationship between rumination, craving and depression in MUD patients, and that depression may play a mediating role between rumination and craving.
This is the first study to investigate the relationship between rumination and craving during withdrawal in methamphetamine dependent patients and the mediating role of depression.Among methamphetamine patients, it was found that reflection was positively correlated with rumination and depression, depression and craving, rumination and craving, and depression plays the mediating role between rumination and craving.These findings suggest that interventions to reduce depression and rumination may also be effective for withdrawal and relapse reduction in methamphetamine patients, providing further rationale for the treatment of methamphetamine patients.
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Trastornos Relacionados con Anfetaminas , Ansia , Depresión , Metanfetamina , Rumiación Cognitiva , Humanos , Masculino , Adulto , Femenino , Trastornos Relacionados con Anfetaminas/psicología , Depresión/psicología , China , Adulto Joven , Persona de Mediana Edad , Encuestas y Cuestionarios , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Psoriasis, a chronic inflammatory condition of the skin, is characterized by an atypical proliferation of epidermal keratinocytes and immune cell infiltration. Orientin is a flavonoid monomer with potent anti-inflammatory activities. However, the therapeutic effects of orientin on psoriasis and the underlying mechanisms have not been elucidated. OBJECTIVE: To investigate the therapeutic effect of orientin on psoriasis and the underlying mechanisms using network pharmacology and experimental studies. METHODS: A psoriasis-like mouse model was established using imiquimod (IMQ). Lipopolysaccharide (LPS) was used to stimulate the RAW264.7 and HaCaT cells in vitro. The therapeutic effects of orientin and the underlying mechanism were analyzed using histopathological, immunohistochemical, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, flow cytometry, and western blotting analyses. RESULTS: Orientin ameliorated skin lesions and suppressed keratinocyte proliferation and immune cell infiltration in the IMQ-induced psoriasis-like mouse model. Additionally, orientin inhibited the secretion of the pro-inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-8, IL-17, and IL-23 in the psoriasis-like mouse model and LPS-induced RAW264.7 and HaCaT cells. Furthermore, orientin mitigated the LPS-induced upregulation of reactive oxygen species and downregulation of IL-10 and glutathione levels. Orientin alleviated inflammation by downregulating the MAPK signaling pathway. CONCLUSION: Orientin alleviated psoriasis-like dermatitis by suppressing the MAPK signaling pathway, suggesting that orientin is a potential therapeutic for psoriasis.
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Antiinflamatorios , Citocinas , Modelos Animales de Enfermedad , Flavonoides , Glucósidos , Células HaCaT , Imiquimod , Queratinocitos , Lipopolisacáridos , Sistema de Señalización de MAP Quinasas , Ratones Endogámicos BALB C , Psoriasis , Animales , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Psoriasis/inducido químicamente , Psoriasis/patología , Ratones , Humanos , Células RAW 264.7 , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Flavonoides/farmacología , Flavonoides/uso terapéutico , Citocinas/metabolismo , Queratinocitos/efectos de los fármacos , Glucósidos/uso terapéutico , Glucósidos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Piel/patología , Piel/efectos de los fármacos , Piel/inmunología , Proliferación Celular/efectos de los fármacos , Masculino , Especies Reactivas de Oxígeno/metabolismo , Dermatitis/tratamiento farmacológico , Dermatitis/patología , Dermatitis/inmunología , Línea CelularRESUMEN
In this work, corn straw was used as raw material, Hummers method and activation were used to adjust the graphite structure in biochar, and preparing straw based biochar (H-BCS) with ultra-high specific surface area (3441.80 m2/g), highly total pore volume (1.9859 cm3/g), and further enhanced physicochemical properties. Compared with untreated straw biochar (BCS), the specific surface area and total pore volume of H-BCS were increased by 47.24 % and 55.85 %, respectively. H-BCS showed good removal ability in subsequent experiments by using chloramphenicol (CP), hexavalent chromium (Cr6+), and crystal violet (CV) as adsorption models. In addition, the adsorption capacities of H-BCS (CP: 1396.30 mg/g, Cr6+: 218.40 mg/g, and CV: 1246.24 mg/g) are not only higher than most adsorbents, even after undergoing 5 cycles of regeneration, its adsorption capacity remains above 80 %, indicating significant potential for practical applications. In addition, we also speculated and analyzed the conjecture about the "graphite-structure regulation" during the preparation process, and finally discussed the possible mechanism during the adsorption processes. We hope this work could provide a new strategy to solve the restriction of biochar performance by further exploring the regulation of graphite structure in carbon materials.
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Carbón Orgánico , Grafito , Contaminantes Químicos del Agua , Carbón Orgánico/química , Grafito/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Adsorción , Eliminación de Residuos Líquidos/métodos , Cromo/química , Contaminación del Agua/prevención & control , Zea mays/química , Purificación del Agua/métodosRESUMEN
This article aims to report the comprehensive and up-to-date analysis and evidence of the insertion rate, expulsion rate, removal rate, and utilization rate of immediate placement of intrauterine devices (IUDs) versus delayed placement after artificial abortion. PubMed, Embase, Cochrane, Web of Science, CNKI, and Wanfang databases were comprehensively searched up to January 12, 2024 for studies that compared immediate versus delayed insertion of IUDs after abortion. The evaluation metrics included the number of IUD insertion after surgical or medical abortions, the frequency of expulsion and removal at 6 months or 1 year, the number of continued usage, pain intensity scores, the number of infections, the duration of bleeding, and instances of uterine perforation during or after IUD insertion. Ten randomized controlled articles were eligible, comprising 11 research projects, of which 3 projects involved the placement of an IUD after surgical abortion, and 8 projects involved the placement of an IUD after medical abortion. This included 2025 patients (977 in the immediate insertion group and 1,048 in the delayed insertion group). We summarized all the extracted evidence. The meta-analysis results indicated that for post-surgical abortions, the immediate insertion group exhibited a higher IUD placement rate than the delayed insertion group. After medical abortions, the immediate insertion group showed higher rates of IUD placement, utilization, and expulsion at 6 months or 1 year. The two groups showed no statistically significant differences in the removal rate, post-insertion infection rate, pain scores during insertion, and days of bleeding during the follow-up period. Compared to delayed placement, immediate insertion of IUDs can not only increase the usage rate at 6 months or 1 year but also enhance the placement rate.
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Aborto Inducido , Dispositivos Intrauterinos , Humanos , Femenino , Dispositivos Intrauterinos/efectos adversos , Aborto Inducido/efectos adversos , Aborto Inducido/métodos , Embarazo , Factores de Tiempo , Remoción de DispositivosRESUMEN
Coprinus comatus is an edible mushroom and its fermented product possesses antioxidant activity. In this study, to further enhance the antioxidant activity and improve the reusability of the strain, calcium alginate hydrogel was used as the carrier for embedding and immobilizing Coprinus comatus. The effects of CaCl2 concentration, sodium alginate concentration, microsphere diameter, and the amount of magnetic particle on the antioxidant activity of fermented products were investigated. The results showed that the magnetic immobilized microsphere prepared by 2.50% CaCl2, 2.00% sodium alginate and 0.50% Fe3O4 had the best fermentation antioxidant activity (EC50 was 0.43 ± 0.01 mg/mL) when the diameter was 5 mm, which increased by 24.56% compared to the initial activity. Besides, the microsphere showed strong reusability, the antioxidant activity was still better than the free strain after being used five times. This study not only enhanced the antioxidant activity of Coprinus comatus fermented product through immobilization, but also provided an effective method for microbial fermentation.
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Anode-free lithium (Li) metal batteries are promising candidates for advanced energy storage, attributed to their appealing characteristics such as high energy density, low cost, and convenient production. However, their major challenges lie in the poor cycling and rate performance owing to the inferior reversibility and kinetics of Li plating and stripping, which significantly hinder their real-world applications. Here, it is demonstrated that deoxyribonucleic acid (DNA), the most important genetic material in nature, can serve as a highly programmable interphase layer for innovation of anode-free Li metal batteries. It is found that the abundant base pairs in DNA can contribute transient Li-N bonds that facilitate homogeneous Li+ flux, thus resulting in excellent Li plating/stripping kinetics and reversibility even at a harsh areal current of 15 mA cm-2. The anode-free LiFePO4 full batteries based on an ultrathin (0.12 µm) and ultralight (≈0.01 mg cm-2) DNA interphase layer show high CEs (≈99.1%) over 400 cycles, corresponding to an increase of ≈186% compared with bare copper (Cu) foil. These results shed light on the excellent programmability of DNA as a new family of interphase materials for anode-free batteries, and provide a new paradigm for future battery innovation toward high programmability, high sustainability, and remarkable electrochemical performance.
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Individuals with a history of childhood abuse (CA, including neglect and abuse by caregivers before the age of 18 years) have more severe substance dependence problems than those without a history of childhood abuse. However, whether a history of CA exacerbates craving and the mechanism of this effect remain largely unknown. The aim of this study was to explore the role of alexithymia in the effects of CA on craving in a large sample of methamphetamine-dependent individuals based on latent vulnerability theory. A total of 324 methamphetamine-dependent individuals who met DSM-5 criteria for substance use disorder were recruited. CA, alexithymia, and craving data were collected from the Childhood Trauma Questionnaire, the Toronto Alexithymia Scale-20, and the Obsessive Compulsive Drug Use Scale, respectively. t tests and ANCOVA were conducted to compare variables between the CA and non-CA groups, while partial correlation and mediation analyses were conducted to examine the potential mediating role of alexithymia in the relationship between CA and craving. Abused methamphetamine-dependent individuals reported higher levels of craving and higher levels of alexithymia than those of non-abused methamphetamine-dependent individuals. Alexithymia partially mediated the link between CA and craving, especially the effect of CA on craving frequency was fully mediated by alexithymia. Our findings reveal that a history of childhood abuse has a lasting effect on craving in stimulant-dependent individuals, and alexithymia contributes to some extent to the severity of substance abuse problems in abused methamphetamine-dependent individuals.
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The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions. Complement proteins C1q, C3, C5, as well as their cleavage products C3a and C5a, along with the associated receptors C3aR, CR3, and C5aR, are believed to have significant implications in the comorbid mechanism. The primary potential mechanisms encompass the involvement of the complement cascade C1q/C3-CR3 in the activation of microglia and synaptic pruning in the amygdala and hippocampus, the role of complement cascade C3/C3a-C3aR in the interaction between astrocytes and microglia, leading to synaptic pruning, and the C3a-C3aR axis and C5a-C5aR axis to trigger inflammation within the central nervous system. We focus on studies on the role of the complement system in the comorbid mechanisms of chronic pain and depression.
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Diabetic nephropathy (DN) and diabetic retinopathy (DR), as microvascular complications of diabetes mellitus, are currently the leading causes of end-stage renal disease (ESRD) and blindness, respectively, in the adult working population, and they are major public health problems with social and economic burdens. The parallelism between the two in the process of occurrence and development manifests in the high overlap of disease-causing risk factors and pathogenesis, high rates of comorbidity, mutually predictive effects, and partial concordance in the clinical use of medications. However, since the two organs, the eye and the kidney, have their unique internal environment and physiological processes, each with specific influencing molecules, and the target organs have non-parallelism due to different pathological changes and responses to various influencing factors, this article provides an overview of the parallelism and non-parallelism between DN and DR to further recognize the commonalities and differences between the two diseases and provide references for early diagnosis, clinical guidance on the use of medication, and the development of new drugs.
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Diabetes Mellitus , Nefropatías Diabéticas , Retinopatía Diabética , Fallo Renal Crónico , Adulto , Humanos , Nefropatías Diabéticas/patología , Retinopatía Diabética/patología , Riñón/patologíaRESUMEN
Enhancer of Zeste Homolog 1 (EZH1) and Enhancer of Zeste Homolog 2 (EZH2) are the key components of polycomb repressive complex 2 (PRC2); however, the roles of these proteins in oral squamous cell carcinoma (OSCC) have yet to be elucidated. In this study, we aimed to determine the respective roles of these proteins in OSCC by investigating the expression levels of EZH1 and EZH2 in OSCC tissues (N = 63) by immunohistochemistry. In addition, we used lentiviruses to construct stable OSCC cell lines that overexpressed EZH1 and EZH2. Then, we investigated these cell lines for cell viability, colony formation capacity, stemness, and epithelial-mesenchymal transition (EMT). Binding competition between EZH1 and EZH2 with PRC2 was further evaluated using Co-immunoprecipitation (Co-IP). Compared with normal tissues, the expression levels of EZH2 in OSCC tissues was up-regulated, while the expression of EZH1 was down-regulated. EZH2 enhanced cell viability, colony formation capacity, stemness, and EMT, while EZH1 did not. Furthermore, analysis indicated that EZH1 and EZH2 bound competitively to PRC2 and influenced the methylation status of H3K27. In conclusion, our findings verified that EZH1 and EZH2 play opposing roles in OSCC and that EZH1 and EZH2 compete as the key component of PRC2, thus affecting the characteristics of OSCC via the methylation of H3K27.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Proteína Potenciadora del Homólogo Zeste 2/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Boca/genética , Complejo Represivo Polycomb 2/genéticaRESUMEN
Our objective is to explore the effect of P53 on the progression of periodontitis by regulating macrophages differentiation both in vitro and in vivo. Eighteen normal and periodontitis gingival tissues were collected for detecting P53 expression and macrophages infiltration by immunofluorescence, real-time PCR (qPCR) and western-blot. The differentiation and the inflammatory cytokines (TNF-α and IL-6) expression of THP-1, RAW264.7 and bone marrow derived macrophage (BMDM) cells, treating with Pifithrin-α (P53 inhibitor) or Nutlin-3a (P53 activator) under lipopolysaccharide (LPS) stimulation, were observed by flow cytometry, qPCR and ELISA. The severity of periodontitis, inflammatory cytokines expression and macrophages infiltration were measured in experimental periodontitis wild-type mice and p53 gene conditional knocked-out (p53-CKO) mice, which were established by ligation and LPS injection. A higher number of P53-positive macrophages was found infiltrated in periodontitis tissues. In vitro experiments showed that compared with Nutlin-3a, the proportion of M1-type macrophages and the expression of TNF-α and IL-6 were higher in Pifithrin-α treated cells under LPS stimulation. In vivo experimental periodontitis mice, the Pifithrin-α intraperitoneal injection group showed greater alveolar bone loss, higher levels of TNF-α and IL-6 secretion and more M1-type macrophages infiltration, while the Nutlin-3a intraperitoneal injection group were observed mild symptoms compared with mice in the periodontitis group. P53-CKO mice exhibited more severe periodontitis and more M1-type macrophages infiltrated in local tissues compared with wild-type mice. The activation of p53 gene could alleviate periodontitis by reducing M1-type macrophage polarization. P53 may serve as keeper in the progression of periodontitis, providing new insights into periodontitis treatment.
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The rise in wearable electronics has witnessed the advancement of self-healable wires, which are capable of recovering mechanical and electrical properties upon structural damage. However, their highly fluctuating electrical resistances in the range of hundreds to thousands of ohms under dynamic conditions such as bending, pressing, stretching and tremoring may seriously degrade the precision and continuity of the resulting electronic devices, thus severely hindering their wearable applications. Here, we report a new family of self-healable wires with high strengths and stable electrical conductivities under dynamic conditions, inspired by mechanical-electrical coupling of the myelinated axon in nature. Our self-healable wire based on mechanical-electrical coupling between the structural and conductive components has significantly improved the electrical stability under dynamic scenarios, enabling precise monitoring of human health status and daily activities, even in the case of limb tremors from simulated Parkinson's disease. Our mechanical-electrical coupling strategy opens a new avenue for the development of dynamically stable electrodes and devices toward real-world wearable applications.
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Major depressive disorder (MDD) is a common complication of diabetes and is often observed alongside diabetic neuropathic pain (DNP) as a comorbidity in diabetic patients. Long non-coding RNA (lncRNA) plays an important role in various pathophysiological processes. The P2X7 receptor is responsible for triggering inflammatory responses, such as pyroptosis, linked to pain and depression. The aim of this study was to investigate the effect of lncRNA MSTRG.81401 on hippocampal pyroptosis induced by the P2X7 receptor in diabetic rats with DNP combined with MDD (DNP + MDD). Our results showed that the expression of lncRNA MSTRG.81401 was significantly elevated in the hippocampus of DNP + MDD rats compared with the control group. Following the administration of shRNA targeting lncRNA MSTRG.81401, a notable elevation in mechanical and thermal pain thresholds was observed in rats with comorbid DNP and MDD. Additionally, significant improvements in depression-like behaviors were evident in the open-field test (OFT), sucrose preference test (SPT), and forced swim test (FST). In the DNP + MDD rats, elevated levels in hippocampal P2X7 receptor mRNA and protein were observed, along with increased co-expression of P2X7 and the astrocytic marker glial fibrillary acidic protein (GFAP). Meanwhile, in DNP + MDD rats, the heightened mRNA expression of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), pyroptosis-related protein Gasdermin D (GSDMD), caspase-1, IL-1ß, IL-18, and TNF-α was detected, in addition to increased serum levels of IL-1ß, IL-18 and TNF-α. After shRNA treatment with lncRNA MSTRG.81401, the above abnormal changes in indicators for pyroptosis and inflammation were improved. Therefore, our study demonstrates that shRNA of lncRNA MSTRG.81401 can alleviate the pain and depression-like behaviors in diabetic rats associated with the comorbidity of DNP and MDD by inhibiting the hippocampal P2X7 receptor-mediated pyroptosis pathway and pro-inflammatory responses. This suggests that the P2X7R/NLRP3/caspase-1 implicated pyroptosis and inflammatory scenario may serve as a potential target for the management of comorbid DNP and MDD in diabetes.
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Trastorno Depresivo Mayor , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Neuralgia , ARN Largo no Codificante , Humanos , Animales , Ratas , ARN Largo no Codificante/genética , Interleucina-18/genética , Receptores Purinérgicos P2X7/genética , Piroptosis/genética , Depresión/genética , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Proteína con Dominio Pirina 3 de la Familia NLR , Factor de Necrosis Tumoral alfa/genética , Neuralgia/genética , Caspasas , Hipocampo , ARN Mensajero , ARN Interferente PequeñoRESUMEN
BACKGROUND: Chemoradiotherapy is a critical treatment for patients with locally advanced and unresectable non-small cell lung cancer (NSCLC), and it is essential to identify high-risk patients as early as possible owing to the high incidence of radiation pneumonitis (RP). Increasing attention is being paid to the effects of endogenous factors for RP. This study aimed to investigate the value of computed tomography (CT)-based radiomics combined with genomics in analyzing the risk of grade ≥ 2 RP in unresectable stage III NSCLC. METHODS: In this retrospective multi-center observational study, 100 patients with unresectable stage III NSCLC who were treated with chemoradiotherapy were analyzed. Radiomics features of the entire lung were extracted from pre-radiotherapy CT images. The least absolute shrinkage and selection operator algorithm was used for optimal feature selection to calculate the Rad-score for predicting grade ≥ 2 RP. Genomic DNA was extracted from formalin-fixed paraffin-embedded pretreatment biopsy tissues. Univariate and multivariate logistic regression analyses were performed to identify predictors of RP for model development. The area under the receiver operating characteristic curve was used to evaluate the predictive capacity of the model. Statistical comparisons of the area under the curve values between different models were performed using the DeLong test. Calibration and decision curves were used to demonstrate discriminatory and clinical benefit ratios, respectively. RESULTS: The Rad-score was constructed from nine radiomic features to predict grade ≥ 2 RP. Multivariate analysis demonstrated that histology, Rad-score, and XRCC1 (rs25487) allele mutation were independent high-risk factors correlated with RP. The area under the curve of the integrated model combining clinical factors, radiomics, and genomics was significantly higher than that of any single model (0.827 versus 0.594, 0.738, or 0.641). Calibration and decision curve analyses confirmed the satisfactory clinical feasibility and utility of the nomogram. CONCLUSION: Histology, Rad-score, and XRCC1 (rs25487) allele mutation could predict grade ≥ 2 RP in patients with locally advanced unresectable NSCLC after chemoradiotherapy, and the integrated model combining clinical factors, radiomics, and genomics demonstrated the best predictive efficacy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonitis por Radiación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neumonitis por Radiación/etiología , Neumonitis por Radiación/genética , Marcadores Genéticos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Tomografía , Estudios Retrospectivos , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
Herein, three enzymes (cellulase, ß-glucosidase, and pectinase) with synergistic effects were co-immobilized on the Eudragit L-100, and the recovery of co-immobilized enzymes from solid substrates were achieved through the reversible and soluble property of the carrier. The optimization of enzyme ratio overcomed the problem of inappropriate enzyme activity ratio caused by different immobilization efficiencies among enzymes during the preparation process of co-immobilized enzymes. The co-immobilized enzymes were utilized to catalytically hydrolyze cellulose from corn straw into glucose, achieving a cellulose conversion rate of 74.45% under conditions optimized for their enzymatic characteristics and hydrolytic reaction conditions. As a result of the reversibility and solubility of the carrier, the co-immobilized enzymes were recovered from the solid substrate after five cycles, retaining 54.67% of the enzyme activity. The aim of this study is to investigate the potential of co-immobilizing multiple enzymes onto the Eudragit L-100 carrier for the synergistic degradation of straw cellulose.