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Fermented soybeans are popular among many for their rich soy sauce-like aroma. However, the precise composition of this aroma remains elusive, with key aroma compounds unidentified. In this study, we screened the candidate genes ilvA and serA in BJ3-2 based on previous multi-omics data, and we constructed three mutant strains, BJ3-2-ΔserA, BJ3-2-ΔilvA, and BJ3-2-ΔserAΔilvA, using homologous recombination to fermented soybeans with varying intensities of soy sauce-like aroma. Our objective was to analyze samples that exhibited different aroma intensities resulting from the fermented soybeans of BJ3-2 and its mutant strains, thereby exploring the key flavor compounds influencing soy sauce-like aroma as well analyzing the effects of ilvA and serA on soy sauce-like aroma. We employed quantitative descriptive sensory analysis (QDA), gas chromatography-olfactometry-mass spectrometry (GC-O-MS), relative odor activity value analysis (rOAV), principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and partial least squares regression analysis (PLSR). QDA revealed the predominant soy sauce-like aroma profile of roasted and smoky aromas. GC-MS detected 99 volatile components, predominantly pyrazines and ketones, across the four samples, each showing varying concentrations. Based on rOAV (>1) and GC-O, 12 compounds emerged as primary contributors to soy sauce-like aroma. PCA and OPLS-DA were instrumental in discerning aroma differences among the samples, identifying five compounds with VIP > 1 as key marker compounds influencing soy sauce-like aroma intensity levels. Differential analyses of key aroma compounds indicated that the mutant strains of ilvA and serA affected soy sauce-like aroma mainly by affecting pyrazines. PLSR analysis indicated that roasted and smoky aromas were the two most important sensory attributes of soy sauce-like aroma, with pyrazines associated with roasted aroma and guaiacol associated with smoky aroma. In addition, substances positively correlated with the intensity of soy sauce-like aroma were verified by additional experiments. This study enhances our understanding of the characteristic flavor compounds in soy sauce-like aroma ferments, provides new perspectives for analyzing the molecular mechanisms of soy sauce-like aroma formation, and provides a theoretical framework for the targeted enhancement of soy sauce-like aroma in various foods.

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BACKGROUND: NOD-like receptor protein 3 (NLRP3) inflammasome activation is indispensable for atherogenesis. Mitophagy has emerged as a potential strategy to counteract NLRP3 inflammasome activation triggered by impaired mitochondria. Our previous research has indicated that dihydromyricetin, a natural flavonoid, can mitigate NLRP3-mediated endothelial inflammation, suggesting its potential to treat atherosclerosis. However, the precise underlying mechanisms remain elusive. This study sought to investigate whether dihydromyricetin modulates endothelial mitophagy and inhibits NLRP3 inflammasome activation to alleviate atherogenesis, along with the specific mechanisms involved. METHODS: Apolipoprotein E-deficient mice on a high-fat diet were administered daily oral gavages of dihydromyricetin for 14 weeks. Blood samples were procured to determine the serum lipid profiles and quantify proinflammatory cytokine concentrations. Aortas were harvested to evaluate atherosclerotic plaque formation and NLRP3 inflammasome activation. Concurrently, in human umbilical vein endothelial cells, Western blotting, flow cytometry, and quantitative real-time PCR were employed to elucidate the mechanistic role of mitophagy in the modulation of NLRP3 inflammasome activation by dihydromyricetin. RESULTS: Dihydromyricetin administration significantly attenuated NLRP3 inflammasome activation and vascular inflammation in mice on a high-fat diet, thereby exerting a pronounced inhibitory effect on atherogenesis. Both in vivo and in vitro, dihydromyricetin treatment markedly enhanced mitophagy. This enhancement in mitophagy ameliorated the mitochondrial damage instigated by saturated fatty acids, thereby inhibiting the activation and nuclear translocation of NF-κB. Consequently, concomitant reductions in the transcript levels of NLRP3 and interleukin-1ß (IL-1ß), alongside decreased activation of NLRP3 inflammasome and IL-1ß secretion, were discerned. Notably, the inhibitory effects of dihydromyricetin on the activation of NF-κB and subsequently the NLRP3 inflammasome were determined to be, at least in part, contingent upon its capacity to promote mitophagy. CONCLUSION: This study suggested that dihydromyricetin may function as a modulator to promote mitophagy, which in turn mitigates NF-κB activity and subsequent NLRP3 inflammasome activation, thereby conferring protection against atherosclerosis.

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Aterosclerosis , Dieta Alta en Grasa , Flavonoles , Células Endoteliales de la Vena Umbilical Humana , Inflamasomas , Mitofagia , Proteína con Dominio Pirina 3 de la Familia NLR , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Mitofagia/efectos de los fármacos , Animales , Flavonoles/farmacología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Aterosclerosis/patología , Aterosclerosis/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Ratones , Humanos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones Endogámicos C57BL , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo

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AIMS: To explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO). METHODS: 11 patients (11 eyes) with ischaemic CRVO and 32 patients (32 eyes) with non-ischaemic CRVO who presented with first-episode unilateral CRVO within 1 month of symptom onset and with no previous intervention were examined by the International Society for Clinical Electrophysiology of Vision standard ERG. RESULTS: A significant amplitude decline and peak time delay in light-adapted (LA) 3 ERG and LA 30 Hz flicker ERG (p<0.05 for all) was found in the ischaemic CRVO eyes, compared with the non-ischaemic CRVO eyes. The b/a amplitude ratio of dark-adapted (DA) 3 ERG, DA 10 ERG and LA 3 ERG was significantly different between the ischaemic and non-ischaemic groups (p<0.05 for all). Regarding oscillatory potentials (OPs), the amplitudes of OP1, OP2 and OP3 as well as the sum of DA 3 OP1-4 amplitudes (∑OPs) showed significant changes (p<0.01 for all) between two groups. No peak time delay of OPs was found between the ischaemic and non-ischaemic CRVO eyes. CONCLUSION: The amplitude of DA 0.01 ERG, components of LA 3 ERG and LA 30 Hz flicker ERG, and the b/a amplitude ratio could be among the most sensitive indicators in patients with acute ischaemic CRVO. The amplitudes of OP1, OP2, OP3 and ∑OPs in the CRVO eyes were reduced to 40% of the control values, showing that this quantitative method is reliable for detecting ischaemic retinal diseases, even in early stage.

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Electrorretinografía , Isquemia , Retina , Oclusión de la Vena Retiniana , Humanos , Oclusión de la Vena Retiniana/fisiopatología , Oclusión de la Vena Retiniana/diagnóstico , Electrorretinografía/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedad Aguda , Isquemia/fisiopatología , Isquemia/diagnóstico , Retina/fisiopatología , Retina/diagnóstico por imagen , Agudeza Visual/fisiología , Adaptación a la Oscuridad/fisiología , Adulto

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BACKGROUND: Observational studies have shown that individual sleep traits habits are potential risk factors for major depression. However, it is not known whether there is a causal relationship between individual sleep traits habits such as continuous sleep duration, short sleep duration, short sleep duration, insomnia, nap during the day, snoring, and major depression. In this study, Mendelian randomization (MR) was used to predict major depressive disorder (MDD) in individuals sleep traits habits. METHODS: Data were obtained from the genome-wide association study (GWAS). Nine MR analysis methods were used: Inverse Variance Weighted (IVW) [fixed effects/multiplicative random effects], simple mode, simple mode, weighted mode, simple median, weighted median, penalised weighted median, and MR-Egger, MR Egger (bootstrap). IVW was used as the main analysis method for the MR analysis of two samples, and the other methods were used as supplements. RESULTS: The results obtained through the IVW method supported a causal relationship between sleep duration and decreased risk of MDD (odds ratio, ORivw: 0.998; 95 % CI: 0.996-0.999, P<0.001). Two-Sample MR, results showed that short sleep duration has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.179; 95 % CI: 1.108-1.255, P<0.001). However, there were no sufficient evidence supported that long sleep duration has a causal effect on the decreased risk of MDD (odds ratio, ORivw: 0.991; 95 % CI: 0.924-1.062, P = 0.793). A significant causal relationship between insomnia and increased risk of MDD was observed (OR: 1.233; 95 % CI: 1.214-1.253, P<0.001). Interestingly, our study also found that daytime napping has a causal effect on the increased risk of MDD (odds ratio, ORivw: 1.519; 95 % CI: 1.376-1.678, P<0.001). The present results did not show a significant causal relationship between snoring and the risk of MDD (ORivw: 1.000; 95 % CI: 0.998-1.002, P = 0.906). Obstructive sleep apnea (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) and morning person (odds ratio, ORivw: 1.021; 95 % CI: 0.972-1.072, P = 0.407) have no causal effect on the increased risk of MDD. LIMITATIONS: The study could not ascertain whether there were genetic differences among different ethnicities, nations, and regions, as it only included participants of European ancestry. CONCLUSIONS: In summary, our research provides genetic evidence for the relationship between individual sleep traits (short sleep duration, insomnia, daytime napping) and the increased risk of MDD. Interventions targeting lifestyle factors may reduce the risk of MDD.

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Trastorno Depresivo Mayor , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Sueño , Humanos , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/epidemiología , Sueño/genética , Factores de Riesgo , Trastornos del Inicio y del Mantenimiento del Sueño/genética , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Polimorfismo de Nucleótido Simple , Masculino , Ronquido/genética , Ronquido/epidemiología , Femenino

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PURPOSE: To investigate the effect of gradient pressure therapy on the prevention of chemotherapy-induced peripheral neuropathy (CIPN) and improvement in activities of daily living (ADL) in patients with breast cancer. METHODS: Eighty female patients with breast cancer treated at Tangshan People's Hospital between October 2022 and July 2023 were selected as research participants and divided into control and intervention, with 40 patients in each group. The control group received routine treatment and care, whereas the intervention group received gradient pressure therapy based on routine treatment and care. Incidence of peripheral neuropathy and the degree of impact on ADL between the two groups were compared after the intervention for cycles 2, 4, and 6. RESULTS: There was no significant difference in the general information between the two groups (P > 0.05). After two intervention cycles, there was no significant difference in the incidence of CIPN, various dimensions of Chemotherapy-Induced Peripheral Neuropathy Assessment Tool (CIPNAT), and total scores between the two groups (P > 0.05). After four intervention cycles, the two groups had a statistically significant difference in the incidence of CIPN, sensory dimension, general activity dimension, and total CIPNAT score (P < 0.05). After six intervention cycles, there was a significant difference in the incidence of CIPN, sensory dimension, fine activity dimension, general activity dimension, and total CIPNAT score between the two groups (P < 0.05), while there was no significant difference in the other dimensions (P > 0.05). CONCLUSIONS: Gradient pressure therapy can effectively prevent or alleviate peripheral neuropathy in patients with breast cancer undergoing chemotherapy and improve their ability to perform ADL. Thus, it is safe, effective, and worthy of clinical application. TRIAL REGISTRATION: RMYY-LLKS-2022-054.

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Actividades Cotidianas , Antineoplásicos , Neoplasias de la Mama , Enfermedades del Sistema Nervioso Periférico , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Persona de Mediana Edad , Antineoplásicos/efectos adversos , Adulto , Presión , Incidencia , Anciano

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PURPOSE: To explore the effects of compression therapy on chemotherapy-induced peripheral neuropathy (CIPN), anxiety, depression, and sleep disorders in breast cancer patients administered taxanes. METHODS: Eighty patients with breast cancer undergoing chemotherapy at Tangshan People's Hospital between October 2022 and July 2023 were randomly divided into control (n = 40) and intervention (n = 40) groups. The control group received routine care, while intervention group received compression therapy in addition to routine care (30 min before the infusion of chemotherapy drugs, patients wore surgical gloves on their hands that were one size smaller than the appropriate size and elastic socks on their feet until 30 min after the infusion). The incidence of CIPN, anxiety, depression, and sleep scores, were compared between these groups before and after compression therapy during chemotherapy cycles 2, 4, and 6. RESULTS: The general characteristics did not differ significantly between the groups (P > 0.05). The CIPN incidence, anxiety and depression scores, and sleep scores also did not differ significantly between the two groups before and after the intervention period (P > 0.05). After the fourth and sixth cycles of intervention, the incidence of CIPN (≥ 1 and ≥ 2), anxiety and depression scores, and sleep scores were significantly lower in the intervention group than in the control group (P < 0.05). CONCLUSION: Compression therapy can effectively reduce the incidence of CIPN, as well as improve the level of anxiety, depression, and sleep disorders in chemotherapy patients. Therefore, medical personnel should closely observe the physical and psychological changes in patients undergoing chemotherapy and provide corresponding preventive measures. REGISTRATION NUMBER: RMYY-LLKS-2022-054. DATE OF REGISTRATION: September 25, 2022.

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Antineoplásicos , Neoplasias de la Mama , Hidrocarburos Aromáticos con Puentes , Enfermedades del Sistema Nervioso Periférico , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Incidencia , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Taxoides , Ansiedad/epidemiología , Antineoplásicos/efectos adversos

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Assembly of macromolecular complexes at correct cellular sites is crucial for cell function. Nuclear pore complexes (NPCs) are large cylindrical assemblies with eightfold rotational symmetry, built through hierarchical binding of nucleoporins (Nups) forming distinct subcomplexes. Here, we uncover a role of ubiquitin-associated protein 2-like (UBAP2L) in the assembly and stability of properly organized and functional NPCs at the intact nuclear envelope (NE) in human cells. UBAP2L localizes to the nuclear pores and facilitates the formation of the Y-complex, an essential scaffold component of the NPC, and its localization to the NE. UBAP2L promotes the interaction of the Y-complex with POM121 and Nup153, the critical upstream factors in a well-defined sequential order of Nups assembly onto NE during interphase. Timely localization of the cytoplasmic Nup transport factor fragile X-related protein 1 (FXR1) to the NE and its interaction with the Y-complex are likewise dependent on UBAP2L. Thus, this NPC biogenesis mechanism integrates the cytoplasmic and the nuclear NPC assembly signals and ensures efficient nuclear transport, adaptation to nutrient stress, and cellular proliferative capacity, highlighting the importance of NPC homeostasis at the intact NE.

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Proteínas Portadoras , Membrana Nuclear , Poro Nuclear , Humanos , Transporte Activo de Núcleo Celular , Células HeLa , Homeostasis , Glicoproteínas de Membrana , Membrana Nuclear/metabolismo , Poro Nuclear/metabolismo , Proteínas de Complejo Poro Nuclear/metabolismo , Proteínas Portadoras/metabolismo

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Queratinocitos , Xantomatosis , Humanos , Xantomatosis/patología , Queratinocitos/patología , Masculino , Femenino , Metabolismo de los Lípidos

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Polypropylene (PP)-based composites have attracted numerous attention as a replacement of prevailing cross-linked polyethylene (XLPE) for high-voltage insulation due to their ease of processing, recyclability, and excellent electrical performance. However, the poor resistances against high-temperature creep and thermal aging are obstacles to practical applications of PP-based thermoplastic high-voltage insulation. To address these problems, in this Letter, we synthesized an impact polypropylene copolymer (IPC) containing multifold long-chain branched (LCB) structures in phases, especially the interfaces between the PP matrix and the rubber phase. The results indicated that the structural stability of LCBIPC was significantly enhanced under extreme conditions. In comparison to IPC (without LCB structures), 24.1% less creep strain and 75.2% less unrecoverable deformation are achieved in LCBIPC at 90 °C. In addition, the thermal aging experiments were performed at 135 °C for 48 and 88 days for IPC and LCBIPC, respectively. The results show that the resistance against thermal aging was also enhanced in LCBIPC, which showed a 133% longer thermal aging life compared to IPC. Further results revealed that the interfacial layer between the PP matrix and the rubber phase was constructed in LCBIPC. The two phases are tightly linked by chemical bonds in LCB structures, leading to enforced constraints of the rubber phase at the micro level and better resistance performance against creep and thermal aging at the macro level. Evidently, the reported eco-friendly LCBIPC thermoplastic insulation shows great potential for applications in high-voltage cable insulation.

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Objective To investigate the expression changes and clinical significance of interleukin-1 recep-tor-associated kinase 1(IRAK1)and tumor necrosis factor receptor-associated factor 6(TRAF6)in patients with septic shock.Methods A total of 142 patients with septic shock admitted from November 2020 to No-vember 2022(septic shock group)were selected as the study subjects,and those who came to the hospital for physical examination during the same period were selected as the control group.Patients with septic shock were divided into survival group(100 cases)and death group(42 cases)according to their survival status after 28 days of hospitalization observation and treatment.The expression changes of IRAK1 and TRAF6 in pa-tients with septic shock were monitored at admission and after 2,4 and 6 days of treatment.The dynamic changes of acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score and sequential organ failure assessment(SOFA)score were recorded.Spearman correlation analysis was used to evaluate the correlation between IRAK1,TRAF6 and APACHE Ⅱ score and SOFA score in septic shock patients.The correlation be-tween IRAK1 and TRAF6 was analyzed by Pearson correlation analysis.Logistic regression was used to ana-lyze the factors influencing survival status of patients with septic shock.The diagnostic value of IRAK1 and TRAF6 in survival of patients with septic shock was analyzed by the receiver operating characteristic curve.Results The relative expression levels of IRAK1 and TRAF6 in septic shock group were significantly lower than those in control group,and APACHE Ⅱ score and SOFA score were significantly higher than those in control group,with statistical significance(P＜0.05).Compared with admission,the relative expression levels of IRAK1 and TRAF6 in 2,4 and 6 days after treatment were significantly increased,while APACHE Ⅱ score and SOFA score were significantly decreased,with statistical significance(P＜0.05).Compared with the death group,the relative expression levels of IRAK1 and TRAF6 in the survival group were higher at each corre-sponding time point,and the APACHE Ⅱ score and SOFA score were lower,with statistical significance(P＜0.05).Correlation analysis showed that IRAK1 and TRAF6 were negatively correlated with APACHE Ⅱscores and SOFA scores in septic shock patients,while IRAK1 and TRAF6 were positively correlated(r=0.688,P＜0.05).IRAK1,TRAF6 and APACHE Ⅱ scores were independent risk factors for survival of septic shock patients(P＜0.05).The AUC of the combined diagnosis of IRAK1 and TRAF6 was significantly larger than that of IRAK1 alone(Z=2.044,P=0.041)and that of TRAF6 alone(Z=2.442,P=0.015).Conclusion The expression of IRAK1 and TRAF6 can evaluate the survival and prognosis of patients with septic shock.

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This article aims to analyze LI Fei's academic thinking and experience in treating facial paralysis.LI Fei proposes that the diagnosis and treatment of facial paralysis should follow the principle of"identify the cause of the disease when it is occured at first time,followed by exploring the pathogenesis of the disease,then differentiating the syndrome and treating the disease,and recognizing the syndrome and treating the disease",and that the basic treatment principle should be"dispelling wind and unblocking the collaterals,regulating the tendons and meridians".In clinical treatment,"put emphasis on anatomy,treat the disease according to symptoms"is the basic policy;meanwhile,integrating Chinese and western theories,combining the anatomical structure of the expression muscle,dynamically judging the recovery of nerves and muscles,and selecting the corresponding empirical acupoints according to the symptoms.LI Fei emphasizes the integration of theories and summarizes the"triple"methods of differentiation by reasoning,staging and symptoms,and the"triple"theory of treatment by regulating menstruation,tendon and spirit,which is worthy of reference in the clinic.

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Objective To investigate the needs and feedback from clinical medical students on the diversified teaching mode adopted by the Department of Endocrinology in Peking Union Medical College Hospital.Methods Questionnaires were distributed to the medicine students who were in clinical rotation in Peking Union Medical Col-lege,and the teaching status and teaching effect was investigated.Results A total of 95 valid questionnaires were received.The attending physicians and the teaching resident physicians performed well in the daily teaching activi-ties.The medical students believed that outpatient training was necessary in addition to ward rotations.After the ro-tation in the endocrinology department,the self-evaluated score of mastery of endocrinology knowledge had been significantly improved,especially in those who rotated in outpatient clinic,suggesting that outpatient teaching was of great significance.In addition,the establishment of a self-learning platform including clinical cases and videos in endocrinology could be used as an important supplementary means for clinical teaching.Conclusions Outpatient training improves learning outcomes of medical students,so must be kept and further strengthened in the future.Building a database of typical clinical cases and teaching videos can improve the training quality.

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Objective:To evaluate the effect of venous excess ultrasound score (VExUS Score) in the acute kidney injury(AKI) in Patients with sepsis, so as to reduce the risk of disease and improve the prognosis of patients.Methods:This experiment was a single-center prospective cohort study. Include septic patients with AKI who were admitted to the Department of Emergency Intensive Care Unit of the First Affiliated Hospital of Anhui Medical University from February 2022 to February 2023, Those with inadequate window, inferior vena cava (IVC) thrombus, age<18 years and known case of cirrhosis with portal hypertension were excluded from the study. Patients underwent ultrasound examination with serial determination till AKI resolved or patient is initiated on dialysis.Results:Totally 86 patients were enrolled for the study. The mean age was (60.43±15.48) with 50 (58.1%) males. Mean sequential organ failure assessment (SOFA) score was (6.23±1.87). 38 patients (44.2%) were in AKI stage 1, while 24 patients (27.9%) were in AKI stage 2 and stage 3 each. 52 patients (60.5%) had VExUS grade Ⅲ. Resolution of AKI injury showed significant correlation with improvement in VExUS grade ( p value 0.003). Similarly, there was significant association between changes in VExUS grade and fluid balance ( p value 0.005). There was no correlation between central venous pressure (CVP), left ventricular function, and right ventricular function with change in VExUS grade. Conclusions:The study shows a significant correlation between the VExUS Score and AKI staging, With improvement in kidney function, there is decline in the VExUS grade as well. Moreover VExUS Score might reliably demonstrate venous congestion and aid in the clinical decision to perform fluid removal.

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The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

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【Objective】 To investigate asymptomatic infection of hepatitis B virus(HBV) among hepatitis B vaccinated donors in Shenzhen, and analyze its serological and molecular characteristics. 【Methods】 The HBsAg ELISA positive blood samples of blood donors born after 1992 were collected. HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were further detected by Roche electrochemiluminescence immunoassay (ECL). BCP/PC and S regions were amplified by Nested-PCRs, HBV DNA quantification were adopted by qPCR simultaneously, and the sequences were also analyzed. 【Results】 A total of 46 632 blood samples of donors(31 612 males and 15 020 females) from December 2020 to January 2022 collected, and 99 samples with HBsAg ELISA positive were screened out. After tested by ECL, Nested-PCRs, and real-time fluorescence PCR, 61 were confirmed HBsAg positive, with the positive rate at 0.13% (61/46 632), including 49 males (0.16%, 49/31 612) and 12 females (0.08%, 12/15 020). The HBsAg positive rate of males was higher than that of females (P<0.05). 50 out of 61 sequences for S region were obtained. By phylogenetic analysis, there were 46 cases of type B (92%, 46/50, 38 males and 8 females), 4 cases of type C (8%, 4/50, 3 males and 1 female). The high frequency mutations observed in S region were N40S (8/46,17.39%), G44E (7/46,15.22%), Q129H/R(6/46,13.04%), Y161F/S(7/46, 15.22%), V179A(4/46,8.70%), S53L(2/4,50%), C69T(2/4,50%) and I126S/T(2/4,50%), including the immune escape mutations Q129R and T/I126A/N/S/T. 【Conclusion】 Hepatitis B vaccination can significantly reduce the positive rate of HBsAg and increase the safety of blood transfusion. The high frequency immune escape mutations have become a potential risk of blood safety, and need to be further explored.

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Objective:To compare the effects of invisible orthodontic appliances without brackets and labial fixed orthodontic appliances on periodontal status and root resorption in orthodontic patients.Methods:A retrospective study was conducted on 102 orthodontic patients who visited the Affiliated Hospital of Jining Medical University from January 2019 to October 2022. According to different treatment methods, they were divided into group A ( n=52) and group B ( n=50). Group A was treated with invisible orthodontic appliances without brackets, while group B was treated with labial fixed orthodontic appliances. We compared two groups of treatment completion time, root resorption, and periodontal health indicators before and after treatment, including plaque index (PLI), gingival index (GI), gingival sulcus bleeding index (SBI), and levels of inflammatory factors in gingival crevicular fluid, including interleukin-1β (IL-1β) and soluble intercellular adhesion molecule-1 (sICAM-1). Results:The completion time of treatment in the Group A was longer than that in the group B [(34.62±4.28)months vs (28.93±3.11)months] ( P<0.01). After treatment, the incidence of root resorption in the group A was 50.96%, while in the group B it was 78.00%. The group A was significantly lower than the group B ( P<0.05), with no root resorption greater than 3 mm in the group A and 0.50% in the group B. After treatment, the levels of PLI, GI, SBI, and IL-1β and sICAM-1 in gingival crevicular fluid increased in both groups, with the group A being lower than group B [(1.26±0.39)points vs (1.73±0.54)points, (1.33±0.25)points vs (2.06±0.46)points, (1.73±0.40)points vs (2.48±0.50)points, (173.74±25.81)ng/ml vs (196.33±31.52)ng/ml, (42.28±5.16)μg/L vs (56.59±7.38)μg/L] (all P<0.05). Conclusions:Although invisible orthodontic appliances without brackets cannot shorten the completion time of treatment, they have advantages in inhibiting root resorption, improving periodontal health, and reducing inflammatory reactions. Clinically, appropriate appliances can be selected based on the specific situation of patients.

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Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn3+SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn2+SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn2+SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn2+SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn2+ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O2• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O2• into the inner sphere, and avoid O2•/Mn2+ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.

RESUMEN

【Objective】 To establish reference intervals for serum soluble transferrin receptor (sTfR) and sTfR/log serum ferritin index (sTfR/lgSF) in apparently healthy adults in the Wuhan area, so as to provide reference for clinical diagnosis and treatment of iron deficiency and iron-deficiency anemia. 【Methods】 A total of 273 individuals from the Wuhan Aisa General Hospital, including health examination participants and blood donors, were selected to measure sTfR, other iron metabolism indicators and high sensitivity C-reactive protein(hsCRP). The sTfR/lgSF values were calculated and reference intervals for sTfR and sTfR /lgSF were established using the percentile method (P2.5 to P97.5). Spearman correlation analysis was used to evaluate the relationships between sTfR, sTfR/lgSF, and other iron metabolism indicators, as well as hsCRP. 【Results】 The sTfR levels (M, mg/L) between males and females (1.01 vs 1.07) were not statistically significant (P>0.05), but the sTfR/lgSF levels if males were significantly lower than those in females (0.45 vs 0.62)(P0.05). The reference interval for STfR was (0.72-1.68) mg/L, the sTfR/lgSF reference interval was (0.31-0.88) for males, and (0.37-1.19) for females. Correlation analysis showed no correlation between sTfR, sTfR/lgSF and hsCRP (r=0.043, P>0.05; r=-0.064, P>0.05), while serum ferritin(SF), serum iron(SI), transferrin saturation(TSAT)were correlated with hsCRP (r=0.128, P0.05), while sTfR/lgSF was significantly correlated with and SF (r=-0.685, P<0.01). 【Conclusion】 Preliminary reference intervals for serum sTfR and sTfR/lgSF in apparently healthy adults in the Wuhan has been established. sTfR and sTfR/lgSF are not affected by inflammatory factors and are significant for identifying iron deficiency in anemia patients with elevated serum ferritin caused by inflammation.

RESUMEN

Immune cells sense the microenvironment to fine-tune their inflammatory responses. Patients with cryopyrin-associated periodic syndrome (CAPS), caused by mutations in the NLRP3 gene, develop autoinflammation triggered by nonantigenic cues such as from the environment. However, the underlying mechanisms are poorly understood. Here, we uncover that KCNN4, a calcium-activated potassium channel, links PIEZO-mediated mechanotransduction to NLRP3 inflammasome activation. Yoda1, a PIEZO1 agonist, lowered the threshold for NLRP3 inflammasome activation. PIEZO-mediated sensing of stiffness and shear stress increased NLRP3-dependent inflammation. Myeloid-specific deletion of PIEZO1/2 protected mice from gouty arthritis. Mechanistically, activation of PIEZO1 triggers calcium influx, which activates KCNN4 to evoke potassium efflux and promotes NLRP3 inflammasome activation. Activation of PIEZO signaling was sufficient to activate the inflammasome in cells expressing CAPS-causing NLRP3 mutants via KCNN4. Last, pharmacological inhibition of KCNN4 alleviated autoinflammation in cells of patients with CAPS and in mice bearing a CAPS mutation. Thus, PIEZO-dependent mechanical inputs boost inflammation in NLRP3-dependent diseases, including CAPS.

Asunto(s)

Síndromes Periódicos Asociados a Criopirina , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Animales , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Mecanotransducción Celular , Síndromes Periódicos Asociados a Criopirina/genética , Inflamación , Canales de Potasio de Conductancia Intermedia Activados por el Calcio , Canales Iónicos/genética

RESUMEN

BACKGROUND: The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. METHODS: A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. RESULTS: In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-ß (IFN-ß) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. CONCLUSIONS: Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-ß-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.

Asunto(s)

Traumatismos por Radiación , Trombocitopenia , Trombosis , Humanos , Animales , Ratones , Megacariocitos/metabolismo , Megacariocitos/patología , Trombocitopenia/etiología , Apoptosis , Nucleotidiltransferasas/metabolismo , Trombosis/metabolismo