Lag projective synchronization of discrete-time fractional-order quaternion-valued neural networks with time delays.

This paper deals with the lag projective synchronization (LPS) problem for a class of discrete-time fractional-order quaternion-valued neural networks(DTFO QVNNs) systems with time delays. Firstly, a DTFOQVNNs system with time delay is constructed. Secondly, linear and adaptive feedback controllers with sign function are designed respectively. Furthermore, through Lyapunov direct method, DTFO inequality technique and Razumikhin theorem, some sufficiency criteria are obtained to ensure that the system in this article can achieve LPS. At last, the significance of the theoretical part of this paper is verified through numerical simulation.

Factors influencing the continuity of evidence-based practice in perioperative airway management for elderly patients with fractures: A qualitative study.

BACKGROUND: More and more evidence-based practices are emerging, but researchers mostly focus on short-term effects, resulting in evidence-based practices not being applied in the clinic in the long term. In this study, we took the evidence-based practice of perioperative airway management in elderly fracture patients as an example and adopted a descriptive phenomenological approach to understand the influencing factors of its sustainability to provide a reference basis for promoting the continuity of evidence-based practice in the clinic. AIM: To explore factors influencing the persistence of evidence-based practice in perioperative airway management in elderly patients with fractures. METHODS: This study was qualitative research. Nine nurses who implemented evidence-based practice in the orthopedic ward of a tertiary comprehensive hospital in Shanghai from September 2023 to October 2023 were selected using purposive sampling as research subjects. Semi-structured interviews were conducted with them, and the data were analyzed using the Colaizzi phenomenological analysis method based on the three dimensions and ten factors of the NHS sustainability model. RESULTS: Three main themes and ten subthemes were identified: Process aspects (benefits to patients, benefits to nurses, lack of follow-up, complex processes); staff aspects (insufficient human resources, inadequate training and education, lack of leadership support); and organizational environment aspects (inadequate infrastructure, poor patient compliance, poor doctor cooperation). CONCLUSION: Human resources, training and education, leadership support, infrastructure, and patient-physician collaboration are important factors influencing the sustainability of evidence-based practice for perioperative airway management in older patients with fractures.

Extracellular Vesicle Isolation and Mass Spectrometry-Based Proteomic Analysis in Arabidopsis thaliana.

Extracellular vesicles (EVs) can transport various biological materials, including proteins, lipids, nucleic acids, and metabolites, through the unconventional protein secretion (UPS) pathway. Plant EVs can be classified into at least three major types: tetraspanin 8 (TET8)-positive EVs, penetration 1 (PEN1)-positive EVs, and exocyst-positive organelle (EXPO)-derived EVs. However, the research progress of plant EVs has been hindered due to the limitations inherent in EV isolation techniques. Moreover, since previous research on plant EVs has primarily focused on the interaction between plants and microbes, the biogenesis, transport, and secretion of plant EVs remain unexplored. Recent advances in centrifugation methods for extraction of apoplastic wash fluids, combined with mass spectrometry-based proteomic analysis, provide approaches to identify regulators and cargoes of plant EVs and thus serve as an important step for future studies on the biogenesis and function of plant EVs. Here, we illustrate detailed methods of EV isolation and mass spectrometry-based proteomic analysis in Arabidopsis.

Whole-Cell Electron Tomography Analysis of Vacuole Biogenesis.

Vacuoles in plant cells are the most prominent organelles that harbor distinctive features, including lytic function, storage of proteins and sugars, balance of cell volume, and defense responses. Despite their dominant size and functional versatility, the nature and biogenesis of vacuoles in plants per se remain elusive and several models have been proposed. Recently, we used the whole-cell 3D electron tomography (ET) technique to study vacuole formation and distribution at nanometer resolution and demonstrated that small vacuoles are derived from multivesicular body maturation and fusion. Good sample preparation is a critical step to get high-quality electron tomography images. In this chapter, we provide detailed sample preparation methods for high-resolution ET in Arabidopsis thaliana root cells, including high-pressure freezing, subsequent freeze-substitution fixation, embedding, and serial sectioning.

Reduced syncytin-1 regulates trophoblast invasion and apoptosis in preeclampsia.

INTRODUCTION: Preeclampsia is a pregnancy-specific disorder characterized by de novo development of hypertension and proteinuria over 20 weeks gestation that has been associated with the dysfunction of trophoblasts. Current evidence suggests that syncytin-1 plays an important role in the non-fusogenic biological activity of trophoblasts, except for specific fusogenic function. However, the underlying mechanism remains unclear. METHODS: The expression and location of syncytin-1 in normal and the late-onset preeclampsia placentas were detected by quantitative real-time PCR, western blotting and immunofluorescence. Morphological and apoptosis analysis were processed in placentas. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Real-time quantitative PCR and immunoblotting were used to calculate syncytin-1 levels in the trophoblast cells before and after syncytin-1 knockdown or overexpression. CCK-8 assay was used to detect the cell viability. TUNEL staining and immunoblotting were processed in trophoblast cells. Transwell assays and wound healing assays were utilize to assess the invasion and migration of trophoblastic cells. Conditional knockout of syncytin-a mouse model was conducted to present the change of placentas in vivo. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Western blotting was used to identify the key proteins of PI3K/Akt pathways and invasion-related proteins in trophoblast cells. RESULTS AND DISCUSSION: Here, reduced syncytin-1 was identified in the late-onset preeclampsia placentas. Reduced syncytin-1 may attenuates the EMT process by promoting apoptosis, inhibiting proliferation and invasion by suppressed PI3K/Akt pathway in trophoblast cells. Our findings provide novel insights into the non-fusogenic biological function of reduced syncytin-1 that may be involves in the pathogenesis of preeclampsia.

Calycosin inhibits the proliferation and metastasis of renal cell carcinoma through the MAZ/HAS2 signaling pathway.

Calycosin (Caly), a flavonoid compound, demonstrates a variety of beneficial properties. However, the specific mechanisms behind Caly's anticancer effects remain largely unexplored. Network pharmacology was used to explore the potential targets of Caly in renal cancer. Additionally, RNA-seq sequencing was used to detect changes in genes in renal cancer cells after Caly treatment. Validation was carried out through quantitative reverse transcription-PCR and Western blot analysis. The luciferase reporter assay was applied to pinpoint the interaction site between MAZ and HAS2. Furthermore, the immunoprecipitation assay was utilized to examine the ubiquitination and degradation of MAZ. In vivo experiments using cell line-derived xenograft mouse models were performed to assess Calycosin's impact on cancer growth. Network pharmacology research suggests Caly plays a role in promoting apoptosis and inhibiting cell adhesion in renal cancer. In vitro, Caly has been observed to suppress proliferation, colony formation, and metastasis of renal cancer cells while also triggering apoptosis. Additionally, it appears to diminish hyaluronic acid synthesis by downregulating HAS2 expression. MAZ is identified as a transcriptional regulator of HAS2 expression. Calycosin further facilitates the degradation of MAZ via the ubiquitin-proteasome pathway. Notably, Caly demonstrates efficacy in reducing the growth of renal cell carcinoma xenograft tumors in vivo. Our findings indicate that Caly suppresses the proliferation, metastasis, and progression of renal cell carcinoma through its action on the MAZ/HAS2 signaling pathway. Thus, Caly represents a promising therapeutic candidate for the treatment of renal cell carcinoma.

The effects of baicalin in depression: preclinical evidence construction based on meta-analysis.

Background: Depression manifests as a mental disorder characterized by a low mood, suicidal tendencies, disturbances in sleep-wake cycles, psychomotor agitation, and pronounced feelings of hopelessness and anhedonia. Baicalin, a natural flavonoid compound, shows significant promise in alleviating depressive symptoms in animals. This study aims to assess the impact of baicalin on experimental models of depression. Methods: A systematic search of electronic databases was conducted using the search terms "baicalin" AND "depression" OR "depressed" OR "anti-depression". Preclinical animal models representing experimental depression were included in the analysis. The risk of bias in the included studies was evaluated using the CAMARADES tools. Results: Baicalin significantly increased sucrose preference test (SPT) [SMD= 21.31, 95%CI (16.32, 26.31), P < 0.00001]. mThe tail suspension test (TST) duration significantly decreased in the baicalin group compared to the model group [SMD = -39.3, 95%CI (-49.71, -28.89), P < 0.0001]. Furthermore, baicalin reduced immobility time in rats subjected to the forced swim test (FST) [SMD = -39.73, 95%CI (-48.77, -30.69) P < 0.0001]. Compared to the model group, baicalin treatment also significantly increased the frequency of crossings in the open field test (OFT) [SMD = 32.44, 95%CI (17.74, 47.13), P < 0.00001]. Conclusion: Baicalin significantly improves the manifestations of depressive symptoms. The effect of baicalin against depression is exerted through its anti-inflammatory actions, inhibition of oxidative stress, regulation of the HPA axis, and restoration of neuroplasticity. Future studies will be needed to further explore how these promising preclinical findings can be translated into clinical treatment for depression. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472181.

Mechanism of Jizhi syrup's prevention and treatment of acute bronchitis based on LPS-iNOS inflammatory mediators' signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jizhi syrup (JZTJ) is composed of eight medicinal herbs, including Houttuynia cordata, Fagopyrum dibotrys, Ilex chinensis, Ephedra sinica, Aster tataricus, Peucedanum praeruptorum, Citrus aurantium and Glycyrrhiza uralensis. It is mainly used for coughing caused by exogenous wind heat. Symptoms include fever, aversion to cold, chest and diaphragm tightness, cough and sore throat; and acute bronchitis and acute exacerbation of chronic bronchitis with the above symptoms. PURPOSE: This study aimed to preliminary analyse the chemical components in the liposoluble part of JZTJ, evaluate the anti-inflammatory effect of JZTJ by using six animal and cell models and predict the target and mechanism of acute bronchitis prevention and treatment with JZTJ. METHODS: The chemical components in the liposoluble fraction of JZTJ (extracted by cyclohexane) were quantitatively analysed using gas chromatography-mass spectrometry (GC-MS). Classic non-specific inflammation models and acute bronchitis models were established to systematically evaluate the anti-inflammatory effect of JZTJ. The anti-inflammatory intensity and characteristics of three doses of JZTJ were comprehensively compared on the basis of principal component analysis method at the cellular and overall animal levels. By using lipopolysaccharides (LPSs) as modelling factors, a RAW264.7 macrophage inflammatory response model and a rat acute bronchitis model were created to study the effect of JZTJ on the in-vitro and - vivo LPS-iNOS-inflammatory mediators' inflammatory signalling pathway to reveal the mechanism of acute bronchitis prevention and treatment by JZTJ at the levels of genes, proteins, and inflammatory mediators. RESULTS: Seventeen alkane and ester compounds were preliminarily qualitatively identified from the lipid soluble fraction of JZTJ: dibutyl phthalate, tetradecane, ridecane, n-hexadecanoic acid, pentadecane, n-decanoic acid, 2,6,10,14,18,22-tetracosahexaene, 2,6,10,15,19,23-hexamethyl-(all-E)-; phenol, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-; hexadecane. JZTJ has a significant inhibitory effect on acute non-specific inflammation, specifically inhibiting 'xylene-induced ear swelling in mice', 'acetic acid-induced increased permeability of abdominal capillaries in mice' and 'egg white-induced foot swelling in rats'. The above effects are most evident in high doses, followed by medium doses, whereas low doses have poorer or no effects. JZTJ can prevent and treat acute bronchitis induced by LPS in mice and rats, significantly improve the pathological changes in patchy interstitial and alveolar bleeding with excessive neutrophil infiltration and inhibit the release of inflammatory mediators by LPS-induced RAW264.7 macrophages. Its mechanism of action may be by downregulating the phosphorylation level of p-ERK1/2 protein, thereby inhibiting inducible nitric oxide synthase (iNOS) mRNA, tumour necrosis factor (TNF)-α MRNA and IL-1ß. The expression levels of genes, such as mRNA and IL-6 mRNA, thereby reducing iNOS, TNF-α and IL-1ß. The expression of proteins in the cytoplasm of lung and bronchial tissue cells reduced the release of downstream inflammatory mediators NO and IL-6. CONCLUSION: Preliminary analysis of the chemical components in the lipid soluble fraction of JZTJ can lay the foundation for subsequent research on its effective components. Evaluating the anti-inflammatory effect of JZTJ is helpful for further research on its mechanism of action. The anti-inflammatory effects are exerted by regulating the inflammatory signalling pathway of LPS-iNOS inflammatory mediators, providing a scientific basis for their clinical application.

Causal relationship between OHSS and immune cells: A Mendelian randomization study.

OBJECTIVE: To confirm the causal relationship between immune cells and Ovarian Hyperstimulation Syndrome. DESIGN: Obtaining data, collecting single nucleotide polymorphisms, detecting instrumental variables heterogeneity, assessing causality, and assessing bidirectional causality. SUBJECTS: A two sample Mendelian study to confirm the causal relationship between immune cells and Ovarian Hyperstimulation Syndrome. EXPOSURE: Immune cell phenotype (including 22 million SNPs from GWAS on 3757 European individuals). MAIN OUTCOME MEASURES: Inverse variance weighting, one-sample analysis, MR-Egger, weighted median and weighted mode are used to assess the causal relationship between 731 immunophenotypes and Ovarian Hyperstimulation Syndrome. The weighted median and Mendelian Randomization multi-effect residuals and Mendelian Randomization multi-effect residuals and outlier tests are used to assess bidirectional causality between this two. RESULTS: After False Discovery Rate correction, 9 immunophenotypes were found to be significantly associated with the risk of Ovarian Hyperstimulation Syndrome. B cell panel: IgD+ AC (OR, 0.90) 、CD19 on CD24+ CD27+ (OR, 0.86) 、BAFF-R on CD20- CD38 (OR, -1.22); Mature T cell group panel: EM DN (CD4 -CD8-) AC (OR, 1.46); Myeloid cell panel: Mo MDSC AC (OR, 1.13) 、CD45 on CD33br HLA-DR+ (OR, 0.87); Monocyte panel: HLA-DR on monocyte (OR, 0.86) 、CCR2 on CD14+ CD16+ monocyte (OR, 1.15) 、cDC panel: HLA-DR on myeloid DC (OR, 0.89). CONCLUSION: This study shows the potential link between OHSS and immune cells by genetic means, providing new ideas for future clinical and basic research.

Understanding the drivers of PM2.5 concentrations in Chinese cities: A comprehensive study of anthropogenic and environmental factors.

Understanding the factors that drive PM2.5 concentrations in cities with varying population and land areas is crucial for promoting sustainable urban population health. This knowledge is particularly important for countries where air pollution is a significant challenge. Most existing studies have investigated either anthropogenic or environmental factors in isolation, often in limited geographic contexts; however, this study fills this knowledge gap. We employed a multimethodological approach, using both multiple linear regression models and geographically weighted regression (GWR), to assess the combined and individual effects of these factors across different cities in China. The variables considered were urban built-up area, land consumption rate (LCR), population size, population growth rate (PGR), longitude, and latitude. Compared with other studies, this study provides a more comprehensive understanding of PM2.5 drivers. The findings of this study showed that PGR and population size are key factors affecting PM2.5 concentrations in smaller cities. In addition, the extent of urban built-up areas exerts significant influence in medium and large cities. Latitude was found to be a positive predictor for PM2.5 concentrations across all city sizes. Interestingly, the northeast, south, and southwest regions demonstrated lower PM2.5 levels than the central, east, north, and northwest regions. The GWR model underscored the importance of considering spatial heterogeneity in policy interventions. However, this research is not without limitations. For instance, international pollution transfers were not considered. Despite the limitation, this study advances the existing literature by providing an understanding of how both anthropogenic and environmental factors, in conjunction with city scale, shape PM2.5 concentrations. This integrated approach offers invaluable insights for tailoring more effective air pollution management strategies across cities of different sizes and characteristics.

Chronic dietary exposure to glyphosate-induced connexin 43 autophagic degradation contributes to blood-testis barrier disruption in roosters.

Glyphosate (GLY) is the most universally used herbicide worldwide and its application has caused extensive pollution to the ecological environment. Increasing evidence has revealed the multi-organ toxicity of GLY in different species, but its male reproductive toxicity in avian species remains unknown. Thus, in vivo and in vitro studies were conducted to clarify this issue. Data firstly showed that chronic GLY exposure caused testicular pathological damage. Intriguingly, we identified and verified a marked down-regulation gap junction gene Connexin 43 (Cx43) in GLY-exposed rooster testis by transcriptome analysis. Cx43 generated by Sertoli cells acts as a key component of blood-testis barrier (BTB). To further investigate the cause of GLY-induced downregulation of Cx43 to disrupt BTB, we found that autophagy activation is revealed in GLY-exposed rooster testis and primary avian Sertoli cells. Moreover, GLY-induced Cx43 downregulation was significantly alleviated by ATG5 knockdown or CQ administration, respectively, demonstrating that GLY-induced autophagy activation contributed to Cx43 degradation. Mechanistically, GLY-induced autophagy activation and resultant Cx43 degradation was due to its direct interaction with ER-α. In summary, these findings demonstrate that chronic GLY exposure activates autophagy to induce Cx43 degradation, which causes BTB damage and resultant reproductive toxicity in roosters.

FTMT-dependent mitophagy is crucial for ferroptosis resistance in cardiac fibroblast.

Metabolic responses to cellular stress are pivotal in cell ferroptosis, with mitophagy serving as a crucial mechanism in both metabolic processes and ferroptosis. This study aims to elucidate the effects of high glucose on cardiomyocytes (CMs) and cardiac fibroblasts (CFs) regarding ferroptosis and to uncover the underlying mechanisms involved. We examined alterations in glycolysis, mitochondrial oxidative phosphorylation (OXPHOS), and mitophagy, which are essential for metabolic adaptations and ferroptosis. High glucose exposure induced ferroptosis specifically in CMs, while CFs exhibited resistance to ferroptosis, increased glycolytic activity, and no change in OXPHOS. Moreover, high glucose treatment enhanced mitophagy and upregulated mitochondrial ferritin (FTMT). Notably, the combination of FTMT and the autophagy-related protein nuclear receptor coactivator 4 (NCOA4) increased under high glucose conditions. Silencing FTMT significantly impeded mitophagy and eliminated ferroptosis resistance in CFs cultured under high glucose conditions. The transcription factor forkhead box A1 (FOXA1) was upregulated in CFs upon high glucose exposure, playing a crucial role in the increased expression of FTMT. Within the 5'-flanking sequence of the FTMT mRNA, approximately -500 nt from the transcription initiation site, three putative FOXA1 binding sites were identified. High glucose augmented the binding affinity between FOXA1 and these sequences, thereby promoting FTMT transcription. In summary, high glucose upregulated FOXA1 expression and stimulated FTMT promoter activity in CFs, thereby promoting FTMT-dependent mitophagy and conferring ferroptosis resistance in CFs.

Variations, effectiveness and its associated factors of a nationwide web-based hypertension management training project in China: insights from a government-led campaign for 1.2 million lay health workers.

OBJECTIVES: To evaluate the effectiveness of a large-scale, web-based, in-service hypertension management training project among lay health workers (LHWs) at primary care health (PHC) settings in China, and to examine the factors contributing to the variations of effectiveness. METHODS: We used data from a web-based national hypertension management training project implemented in 2018, it was designed to facilitate LHWs to learn, understand, and apply the relevant knowledge and skills in hypertension management through providing training courses by use of the web-based platform with unified standards. All LHWs were required to participate in the exams before and after training to acquire scores for the use of evaluating their performance of hypertension management knowledge. We first used descriptive analysis to present the variations of effectiveness in hypertension management knowledge among LHWs by important subgroups. Afterwards, we used multilevel logistic regression to examine the individual and regional factors contributing to the variations and quantify the magnitude of how these factors affected training effectiveness. RESULTS: There were 1,208,610 LHWs who completed training and were certificated. Nationally, the scores of LHWs increased significantly from 62.87 ± 21.14 out of 100 in the pre-test to 88.30 ± 11.31 in the post-test by 25.43 (95% confidence interval [CI]: 25.40-25.47). Training contents involved in antihypertensive medication showed the lowest score (54.36) in the pre-test and soared the most after training, up to 84.22 by 54.94%. Individual factors associated with disparities in the knowledge of hypertension management decreased substantially after training, which included sex, age, education, practice type, professional level, and hierarchy of working institutions. Geographical variations were shown at the provincial level, with the majority of them being explained by factors at the regional level. CONCLUSIONS: Accessible web-based training modality, government efforts, accompanied with experiences derived from the training, could be generalized to other low- and middle-income countries in facilitating the hypertension management capacity of LHWs. Localization and evaluation is warranted on the way to its further application.

Jejunostomy feeding plus oral feeding versus intravenous nutrition plus oral feeding after esophageal cancer resection: a comparative retrospective cohort study.

Background: There are multiple choices for the nutritional management mode after esophageal cancer surgery. Currently, there is still controversy regarding which nutritional management mode has an impact on the postoperative recovery and overall survival (OS) of patients. This study aims to compare the differences between two commonly used clinical nutritional management modes: jejunostomy feeding plus oral intake (JF plus OI) and intravenous nutrition plus oral intake (IN plus OI), in terms of short-term efficacy and 3-year OS, in order to further explore the optimal mode of enteral nutrition management after esophageal cancer surgery. Methods: We evaluated esophageal cancer patients who underwent radical surgery at Union Hospital of Fujian Medical University between January 1, 2010 and January 1, 2020. The purpose of this analysis was to compare the perioperative complications, Nutritional Risk Screening 2002 (NRS2002) nutritional scores at 1 week, 2 weeks, 1 month, and 3 months after surgery, as well as the 3-year OS rates, between two different nutritional management approaches: JF plus OI and IN plus OI following esophageal cancer surgery. Results: Among the 822 patients included, 668 and 154 patients belonged to JF plus OI and IN plus OI groups, respectively. After propensity score matching, 149 patients per group were evaluated. The amount of gastric drainage fluid was higher in the IN plus OI group (P<0.05), and the incidence of postoperative gastrointestinal emptying disorder and intestinal obstruction was significantly higher in the JF plus OI group (P<0.05). The IN plus OI group had a higher incidence of perioperative hypoproteinemia (P<0.05), and a higher risk of malnutrition in 2 weeks after surgery (P<0.05). The 3-year OS was not significantly different (P>0.05). Conclusions: JF plus OI may be the preferable nutritional management approach after esophageal cancer resection as it can potentially reduce perioperative nutritional deficiency. However, attention should be paid to the risk of gastrointestinal emptying and intestinal obstruction associated with JF.

Metformin relieves bone cancer pain by reducing TGFßRI-TRPV1 signaling in rats.

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFß1 in the metastatic bone tissue, and raised the expression of TGFßRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFßRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFß1, TGFßRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFß1-TGFßRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

Comprehensive Multiple Risk Factor Control in Type 2 Diabetes to Mitigate Heart Failure Risk: Insights From a Prospective Cohort Study.

OBJECTIVE: The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. RESEARCH DESIGN AND METHODS: This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. RESULTS: During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. CONCLUSIONS: Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.

Sparse Bayesian Learning for Switching Network Identification.

Learning dynamical networks based on time series of nodal states is of significant interest in systems science, computer science, and control engineering. Despite recent progress in network identification, most research focuses on static structures rather than switching ones. Therefore, this article develops a method for identifying the structures of switching networks by exploring and leveraging both temporal and spatial structural information that characterizes the switching process. The proposed method employs a new sparse Bayesian learning algorithm based on coupled hyperblocks to estimate unknown switching instants. Experimental results on benchmark artificial and real networks are elaborated to demonstrate the effectiveness and superiority of the proposed method.

A novel chemical probe based on the salamo-Co(II) complex for the highly selective fluorescence detection of tyrosine.

A new and rare Salamo-Co(II) complex probe L-Co2+ was designed and synthesised. The structure of the [Co3(L)2(µ-OAc)2(MeOH)2]⋅2H2O complex was obtained by X-ray diffraction experiments. Three Co(II) atoms are in a line in the complex, and all Co(II) atoms form a 6-coordinated octahedral configuration. The probe L-Co2+ selectively recognises tyrosine in DMF/H2O (8:2, v/v). Upon addition of tyrosine, the fluorescence intensity of L-Co2+ was enhanced in a short time. The probe showed high selectivity and sensitivity for tyrosine, detection limit is 4.27 × 10-8 M. The recognition mechanism of probe L-Co2+ for Tyr was inferred by FT-IR spectra, UV spectroscopy, ESI mass spectra and DFT calculations. Finally, due to the simplicity and specificity of the identification process, the probe was also subjected to a test paper experiment and a milk assay.

Knocking down EGR1 inhibits nucleus pulposus cell senescence and mitochondrial damage through activation of PINK1-Parkin dependent mitophagy, thereby delaying intervertebral disc degeneration.

Mitophagy plays a crucial role in maintaining the homeostasis of intervertebral disc (IVD). Early Growth Response 1 (EGR1), a conservative transcription factor, is commonly upregulated under oxidative stress conditions and participates in regulating cellular senescence, apoptosis, and inflammatory responses. However, the specific role of EGR1 in nucleus pulposus (NP) cell senescence and mitophagy remains unclear. In this study, through bioinformatics analysis and validation using human tissue specimens, we found that EGR1 is significantly upregulated in IVD degeneration (IDD). Further experimental results demonstrate that knockdown of EGR1 inhibits TBHP-induced NP cell senescence and mitochondrial dysfunction while promoting the activation of mitophagy. The protective effect of EGR1 knockdown on NP cell senescence and mitochondrion disappears upon inhibition of mitophagy with mdivi1. Mechanistic studies reveal that EGR1 suppresses NP cell senescence and mitochondrial dysfunction by modulating the PINK1-Parkin dependent mitophagy pathway. Additionally, EGR1 knockdown delays acupuncture-induced IDD in rats. In conclusion, our study demonstrates that under TBHP-induced oxidative stress, EGR1 knockdown mitigates NP cell senescence and mitochondrial dysfunction through the PINK1-Parkin dependent mitophagy pathway, thereby alleviating IDD.

A positive loop between relish and cuticle proteins and their roles in regulating AMPs expression during bacterial infection in Eriocheir sinensis.

Cuticle proteins (CPs) are the vital components of the cuticle and chitin lining covering the digestive tract of crustaceans. In this study, four new CP genes (designated as EsCP3, EsCP4, EsCP5, and EsCP8) were initially cloned and identified from the Chinese mitten crab Eriocheir sinensis. EsCP3/4/5/8 included 375, 411, 381, and 570 bp open reading frame encoding 124, 136, 126, and 189 amino acid proteins, respectively. Except for EsCP8, EsCP3/4/5 all contained a Chitin_bind_4 domain. EsCP3/4/5/8 were clustered into different groups in the phylogenetic tree. Quantitative real-time PCR results indicated that four EsCP genes have different patterns of tissue distribution. Changes in the expression levels of these four EsCP genes were observed in the intestine of crabs under Vibrio parahaemolyticus challenge. RNA interference assay showed that the knockdown of EsCPs in the intestine could inhibit the expression of antimicrobial peptides (AMPs), including crustins and anti-lipopolysaccharide factors. In addition, the knockdown of EsRelish in the intestine decreased the expression levels of these four EsCP genes. These results indicated that EsCPs were involved in regulating the expression of AMPs, and EsCPs were regulated by EsRelish.