[Lysine Succinylation:A New Perspective in the Treatment of Cardiovascular Diseases].

With the continuous development of identification technologies such as mass spectrometry,omics,and antibody technology,post-translational modification (PTM) has demonstrated increasing potential in medical research.PTM as a novel chemical modification method provides new perspectives for the research on diseases.Succinylation as a novel modification has aroused the interest of more and more researchers.The available studies about succinylation mainly focus on a desuccinylase named sirtuin 5.This enzyme plays a key role in modification and has been preliminarily explored in cardiovascular studies.This paper summarizes the influencing factors and regulatory roles of succinylation and the links between succinylation and other PTMs and reviews the research progress of PTMs in the cardiovascular field,aiming to deepen the understanding about the role of this modification and give new insights to the research in this field.

Alternative Polyadenylation Regulatory Factors Signature for Survival Prediction in Kidney Renal Cell Carcinoma.

Background: Alternative polyadenylation (APA) plays a vital regulatory role in various diseases. It is widely accepted that APA is regulated by APA regulatory factors. Objective: Whether APA regulatory factors affect the prognosis of renal cell carcinoma remains unclear, and this is the main topic of this study. Methods: We downloaded the transcriptome and clinical data from The Cancer Genome Atlas (TCGA) database. We used the Lasso regression system to construct an APA model for analyzing the relationship between common APA regulatory factors and renal cell carcinoma. We also validated our APA model using independent GEO datasets (GSE29609, GSE76207). Results: It was found that the expression levels of 5 APA regulatory factors (CPSF1, CPSF2, CSTF2, PABPC1, and PABPC4) were significantly associated with tumor gene mutation burden (TMB) score in renal clear cell carcinoma, and the risk score constructed using the expression level of 5 key APA regulatory factors could be used to predict the outcome of renal clear cell carcinoma. The TMB score is associated with the remodeling of the immune microenvironment. Conclusions: By identifying key APA regulatory factors in renal cell carcinoma and constructing risk scores for key APA regulatory factors, we showed that key APA regulators affect prognosis of renal clear cell carcinoma patients. In addition, the risk score level is associated with TMB, indicating that APA may affect the efficacy of immunotherapy through immune microenvironment-related genes. This helps us better understand the mRNA processing mechanism of renal clear cell carcinoma.

Stereo Visual Servoing Control of a Soft Endoscope for Upper Gastrointestinal Endoscopic Submucosal Dissection.

Quickly and accurately completing endoscopic submucosal dissection (ESD) operations within narrow lumens is currently challenging because of the environment's high flexibility, invisible collision, and natural tissue motion. This paper proposes a novel stereo visual servoing control for a dual-segment robotic endoscope (DSRE) for ESD surgery. Departing from conventional monocular-based methods, our DSRE leverages stereoscopic imaging to rapidly extract precise depth data, enabling quicker controller convergence and enhanced surgical accuracy. The system's dual-segment configuration enables agile maneuverability around lesions, while its compliant structure ensures adaptability within the surgical environment. The implemented stereo visual servo controller uses image features for real-time feedback and dynamically updates gain coefficients, facilitating rapid convergence to the target. In visual servoing experiments, the controller demonstrated strong performance across various tasks. Even when subjected to unknown external forces, the controller maintained robust performance in target tracking. The feasibility and effectiveness of the DSRE were further verified through ex vivo experiments. We posit that this novel system holds significant potential for clinical application in ESD surgeries.

Tumor polo-like kinase 4 protein expression reflects lymphovascular invasion, higher Federation of Gynecology and Obstetrics stage, and shortened survival in endometrial cancer patients who undergo surgical resection.

BACKGROUND: Polo-like kinase 4 (PLK4) serves as a marker for tumor features and poor outcomes in cancers. This study aimed to explore the associations of tumor PLK4 protein expression with tumor characteristics and survival in endometrial cancer (EC) patients who underwent surgical resection. METHODS: This study included 142 EC patients who underwent surgical resection. Tumor tissue samples were obtained for tumor PLK4 protein expression detection via immunohistochemistry (IHC). RESULTS: Among EC patients, 26.1% had a PLK4 IHC score of 0, 24.6% had a score of 1-3, 27.5% had a score of 4-6, and 21.8% had a score of 7-12. Tumor PLK4 protein expression positively associated with lymphovascular invasion (P = 0.008) and Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.005). Disease-free survival (DFS) was not different between patients with tumor PLK4 IHC scores > 0 and ≤ 0 (P = 0.154) but was reduced in patients with scores > 3 vs. ≤ 3 (P = 0.009) and > 6 vs. ≤ 6 (P < 0.001). Similarly, overall survival (OS) was not different between patients with scores > 0 and ≤ 0 (P = 0.322) but was shorter in patients with scores > 3 vs. ≤ 3 (P = 0.011) and > 6 vs. ≤ 6 (P = 0.006). After adjustment, a tumor PLK4 IHC score > 6 (vs. ≤ 6) (hazard ratio (HR): 3.156, P = 0.008) or > 3 (vs. ≤ 3) (HR: 3.918, P = 0.026) was independently associated with shortened DFS and OS. CONCLUSION: A tumor PLK4 IHC score > 6 or > 3 associates with shortened DFS and OS in EC patients who undergo surgical resection.

A Robotized Soft Endoscope with Stereo Vision for Upper Gastrointestinal Endoscopic Submucosal Dissection (ESD).

This work presents a novel dual-segment flexible robotic endoscope designed to enhance reachability and dexterity during ESD surgery. The proposed system is capable of executing multi-angle cutting operations at a small angle relative to the lesion surface, allowing for efficient en-bloc resection. Additionally, the system incorporates two calibrated RGB cameras and a depth estimation algorithm to provide detailed 3D information of the tumour, which is used to guide the control framework. A stereo visual servoing controller is also implemented to improve path-following performance during surgery. Experiments results indicate that the proposed system improves motion stability and precision. The root means square error (RMSE) of circle path following is 1.1991mm with a maximum of 1.4751mm. Ex-vivo testing demonstrates its significant potential for use in endoscopic surgery.

Correlation between the systemic immune-inflammation indicator (SII) and serum ferritin in US adults: a cross-sectional study based on NHANES 2015-2018.

BACKGROUND & OBJECTIVE: The systemic immune-inflammation indicator (SII) has been extensively employed in various diseases for course change, treatment efficacy, or prediction, whereas whether it applies to iron overload or iron deficiency remains unclear. This study aimed at investigating the correlation between SII and serum ferritin in people aged over 20 in the US. METHODS: The measurements of the systemic immune-inflammation indicator (SII = platelet count × neutrophil-to-lymphocyte ratio) and serum ferritin of 5491 participants in the NHANES database served as the independent and dependent variables for the present cross-sectional study, respectively. Moreover, the correlation was investigated through and used multiple linear regression, smooth curve fitting, and threshold effect. RESULTS: After rigorous inclusion and exclusion of 19,225 participants, a grand total of 5,491 participants conforming to the requirements were covered for relevant analysis. SII showed a significant negative correlation with serum ferritin in unregulated ([ß=-0.05,p < 0.0001], micro-regulated [ß=-0.02,p = 0.0010], and fully regulated models[ß=-0.03,p < 0.0001]). In all participants, the negative correlation between SII and serum ferritin served as a non-linear relationship, as indicated by a smooth curve. Subsequently, in the subgroup analysis (stratified by age, sex, and race) fitted by the smooth curve, the above-mentioned negative correlation turned out to be nonlinear in the subgroups aged ≥40 years, Non-Hispanic Black and female, with U-shaped inflection points reaching 874.59, 930.22, and 615 for SII in the above-described subgroups, respectively. The correlation between SII and serum ferritin in Mexican American, Other Hispanic, Non-Hispanic White, and those aged less than 40 developed a linear negative correlation. CONCLUSIONS: To the best of our knowledge, this study examined the correlation between SII and serum ferritin for the first time. The correlation between SII and serum ferritin was varied with sex, age and race in people aged 20 and older. Therefore, higher or lower SII may be relevant for identifying iron overload and iron deficiency.

Bibliometric analysis of scientific papers on adverse reactions to COVID-19 vaccines published between 2019 and 2023.

The Coronavirus Disease 2019 (COVID-19) pandemic has now persisted globally for four years, resulting in a staggering death toll of over 4 million individuals. The COVID-19 vaccine has emerged as a highly effective tool in controlling the spread of this virus. However, as the number of individuals receiving COVID-19. In this context, the investigation of adverse reactions related to COVID-19 vaccines holds paramount importance in relevant research. The purpose is to evaluate the current research status regarding adverse reactions associated with COVID-19 vaccines, offering insights for future research. A total of 3,746 articles were included in this analysis, and there has been a notable upward trajectory in the volume of published articles. The CiteSpace v6.1.R6, VOSviewer, SCImago Graphica, and Excel 2019 were employed to analyze and visualize the results. The institutions, countries, journals, authors, co-cited references, and keywords of these articles were analyzed. Furthermore, this study delves into the characteristics of articles on adverse reactions associated with COVID-19 vaccines. It was observed that the number of studies on COVID-19 vaccines has increased year by year since 2019 and witnessed a surge in output in 2021. The vast majority of studies have affirmed the overall safety of COVID-19 vaccines, with adverse reactions tending to be more concentrated in specific diseases. These findings provide valuable ideas for future research in this field and suggest the importance of strengthening international cooperation on adverse reactions to COVID-19 vaccines.

Association between serum soluble α-klotho and bone mineral density (BMD) in middle-aged and older adults in the United States: a population-based cross-sectional study.

BACKGROUND: Osteoporosis is a degenerative disease defined by low bone mineral density, has a high prevalence, and causes fractures at multiple sites throughout the body, greatly affecting the quality of patients. α-Klotho is an endocrine factor involved in the regulation of various metabolic processes in humans, and its role in bone metabolism has attracted widespread attention. The relationship between α-klotho and bone mineral density has not been uniformly recognized, and no large-scale correlation analysis has been conducted in the middle-aged and elderly population. OBJECTIVE: To determine the relationship between α-klotho and bone mineral density in middle-aged and elderly people. METHODS: Population data of 3120 individuals aged 40-79 years were obtained from the NHANES database for the period 2011-2016. Regression analysis was performed using a general linear model with serum α-klotho as the independent variable and total bone mineral density, thoracic bone mineral density, lumbar bone mineral density, pelvic bone mineral density, and trunk bone mineral density as the dependent variables, respectively. The generalized additive model was also used for smoothing curve fitting and threshold effect analysis. RESULTS: Serum α-klotho was positively correlated with total bone mineral density at lg (Klotho) < 2.97 and with thoracic bone mineral density at lg (Klotho) > 2.69 (ß = 0.05, p = 0.0006), and negatively correlated (ß = -0.27, p = 0.0341) with lumbar bone mineral density at lg (Klotho) < 2.69. It also positively correlated with trunk bone mineral density (ß = 0.027, p = 0.03657) and had no segmental effect but did not correlate with pelvic bone mineral density. The positive association of serum α-klotho with those aged 40-49 years, female, non-Hispanic White, and without hypertension was clearer. In the population with diabetes, a significantly positive association between total (ß = 0.15, p = 0.01), thoracic (ß = 0.23, p = 0.0404), and lumbar (ß = 0.22, p = 0.0424) bone mineral density and α-klotho was observed. CONCLUSIONS: α-Klotho has different relationships with total, thoracic, lumbar, and trunk bone mineral density. Among them, the positive correlation between α-klotho and trunk bone mineral density is more valuable for predicting osteoporosis. The significant effect of α-klotho on bone mineral density in diabetes patients suggests its potential as a predictive marker of diabetes progression.

Relationship between bisphenol A and the cardiovascular disease metabolic risk factors in American adults: A population-based study.

BACKGROUND: Bisphenol A (BPA) is widely used in personal care and consumer products. However, no study has reported a specific relationship between BPA concentrations and metabolic hazardous elements for cardiovascular diseases (CVDs). Consequently, in this study, we used six years of population-based NHANES data (2011-2016) to analyse the association between BPA concentrations and metabolic risk factors for CVDs. METHODS: A total of 1467 participants were enrolled in our project. The participants in the study were divided into quartiles based on BPA levels (Q1: ≤0.6 ng/ml, Q2: 0.7-1.2 ng/ml, Q3: 1.3-2.3 ng/ml, Q4: ≥2.4 ng/ml). This study used multiple linear and multivariate logistic regression models to determine the association among BPA concentrations and CVD metabolic risk factors. RESULTS: When the concentration of BPA was in Q3, fasting glucose concentrations were decreased by 3.87 mg/dl, and 2-h glucose concentrations were decreased by 16.24 mg/dl. When the concentration of BPA was in Q4, fasting glucose concentrations were decreased by 12.15 mg/dl, and diastolic blood pressure was increased by 2.08 mmHg. At the same time, compared to participants in the first quartile (Q1), those from the fourth quartile (Q4) of BPA concentrations had 21% higher odds of hypertension, 30% higher odds of obesity, 30.2% higher odds of central obesity, 4.5% higher odds of elevated HbA1c, 17% higher odds of elevated non-HDL cholesterol, and 60.8% higher odds of diabetes (compared to the lowest quartile, Q1). CONCLUSIONS: We found that higher concentrations of BPA were linked with a higher metabolic risk for CVDs. Further regulation of BPA may need to be considered for the prevention of CVDs in adults.

Corticospinal circuit neuroplasticity may involve silent synapses: Implications for functional recovery facilitated by neuromodulation after spinal cord injury.

Spinal cord injury (SCI) leads to devastating physical consequences, such as severe sensorimotor dysfunction even lifetime disability, by damaging the corticospinal system. The conventional opinion that SCI is intractable due to the poor regeneration of neurons in the adult central nervous system (CNS) needs to be revisited as the CNS is capable of considerable plasticity, which underlie recovery from neural injury. Substantial spontaneous neuroplasticity has been demonstrated in the corticospinal motor circuitry following SCI. Some of these plastic changes appear to be beneficial while others are detrimental toward locomotor function recovery after SCI. The beneficial corticospinal plasticity in the spared corticospinal circuits can be harnessed therapeutically by multiple contemporary neuromodulatory approaches, especially the electrical stimulation-based modalities, in an activity-dependent manner to improve functional outcomes in post-SCI rehabilitation. Silent synapse generation and unsilencing contribute to profound neuroplasticity that is implicated in a variety of neurological disorders, thus they may be involved in the corticospinal motor circuit neuroplasticity following SCI. Exploring the underlying mechanisms of silent synapse-mediated neuroplasticity in the corticospinal motor circuitry that may be exploited by neuromodulation will inform a novel direction for optimizing therapeutic repair strategies and rehabilitative interventions in SCI patients.

Nanoparticles based composite coatings with tunable vascular endothelial growth factor and bone morphogenetic protein-2 release for bone regeneration.

Bone healing is a complex cascade involving precisely coordinated spatiotemporal presentation of multiple growth factors (GFs), including osteogenic and angiogenic GFs, and each stage of bone healing requires varying types and content of GFs. In this study, we fabricated a composite nanocoating with tunable vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) that was coated on the surface of a polydopamine (PDA)-decorated tertiary calcium phosphate (TCP) scaffold using VEGF-loaded chitosan/bovine serum albumin nanoparticles (CS/BSA-NPs) and BMP-2-loaded poly-L-lysine/oxidized alginate nanoparticles (PLL/OALG-NPs). It was found that VEGF could be efficiently released to promote vascularization in early bone repair stages due to the rapid biodegradation of CS/BSA-NPs, while bone formation can be promoted by a sustained release of BMP-2 from the slowly degrading PLL/OALG-NPs. The composite coating and TCP scaffold can be conjugated due to the excellent adhesive property of PDA. The composite coating can achieve the rapid release of VEGF and sustained release of BMP-2, which can activate GFs for accelerating bone healing.

Cytokine storm and targeted therapy in hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The central pathogenesis is an explosive cytokine storm characterized by a significant increase in proinflammatory cytokines, including IL-1ß, IL-6, IL-18, IFN-γ, and TNF-α. Meanwhile, negative regulatory factors, such as IL-10 and TGF-ß, are also related to the production of HLH. Exploring the specific mechanism of cytokine storms could provide ideas regarding targeted therapy, which could be helpful for early treatment to reduce the mortality of HLH. Although some research has focused on the advantages of targeted therapies, there is still a lack of a comprehensive discourse. This article attempts to summarize the mechanisms of action of various cytokines and provide a therapeutic overview of the current targeted therapies for HLH.

Deletion of cox7c Results in Pan-Azole Resistance in Aspergillus fumigatus.

In Aspergillus fumigatus, the most prevalent resistance to azoles results from mutational modifications of the azole target protein Cyp51A, but there are non-cyp51A mutants resistant to azoles, and the mechanisms underlying the resistance of these strains remain to be explored. Here, we identified a novel cytochrome c oxidase, cox7c (W56*), nonsense mutation in the laboratory and found that it caused reduced colony growth and resistance to multiantifungal agents. Meanwhile, we revealed that cold storage is responsible for increased tolerance of conidia to itraconazole (ITC) stress, which further advances azole-resistant mutations (cryopreservation→ITC tolerance→azole resistance). The deletion or mutation of cox7c results explicitly in resistance to antifungal-targeting enzymes, including triazoles, polyenes, and allylamines, required for ergosterol synthesis, or resistance to fungal ergosterol. A high-performance liquid chromatography (HPLC) assay showed that the cox7c knockout strain decreased intracellular itraconazole concentration. In addition, the lack of Cox7c resulted in the accumulation of intracellular heme B. We validated that an endogenous increase in, or the exogenous addition of, heme B was capable of eliciting azole resistance, which was in good accordance with the phenotypic resistance analysis of cox7c mutants. Furthermore, RNA sequencing verified the elevated transcriptional expression levels of multidrug transport genes. Additionally, lower itraconazole-induced reactive oxygen species generation in mycelia of a cox7c-deletion strain suggested that this reduction may, in part, contribute to drug resistance. These findings increase our understanding of how A. fumigatus's direct responses to azoles promote fungal survival in the environment and address genetic mutations that arise from patients or environments.

Bibliometric evaluation of 2011-2021 publications on hydrogen sulfide in heart preservation research.

Background: Hydrogen sulfide (H2S) is known for its unpleasant odor and severe toxicity. However, an in-depth study of H2S showed that it can be used as an important messenger, which can play important physiological and pathological roles in vitro and in vivo. In recent years, the application of H2S in the field of cardiac preservation has attracted the interest and attention of scholars worldwide. H2S plays an effective and protective role in cardiac ischemia/reperfusion injury through antioxidant, anti-inflammatory, and antiapoptotic mechanisms. Objective: The purpose of this study is to analyze the current scientific achievements on the application of H2S in the field of cardiac preservation and to provide new ideas for further research. Methods: TS = ("hydrogen sulfide" OR "hydrogen sulfide") AND TS = ("cardiac" OR "heart" OR "myocardium" OR "hearts") AND TS = ("reperfusion" or "transplantation" or "implanted" or "transplant" or "implantation" or "migration" or "preservation" or "grafting" OR "ischemia" OR "perfusion" or "conservation" or "preserve" or "reservation") AND DT = (Article OR Review) AND LA = (English) were used as search strategies for data collection from the Science Citation Index-Expanded database of the Web of Science Core Collection. CiteSpace 5.8. R3 and Microsoft Office Excel 2019 were used for data analysis. Results: A total of 429 related articles were included, and the total number of articles showed a fluctuating upward trend. We used CiteSpace 5.8. R3 and Microsoft Excel 2019 to evaluate and visualize the results, analyzing institutions, countries, journals, authors, co-cited references, and keywords. Conclusions: As increasing evidence shows that H2S plays an indispensable role in the field of cardiac preservation, its mechanistic research and clinical application may become the main focus of future research.

Direct-Contact Low-Frequency Ultrasound and Pulse Lavage Eradicates Biofilms on Implant Materials In Vitro.

Pulse lavage (PL) debridement and ultrasound are both known to be the treatment of biofilm-related periprosthetic joint infection (PJI). However, the efficacy of these in combination is unknown in eradicating biofilm from the orthopaedic metal implant surface. This study was conducted to understand the efficacy of PL and ultrasound in combination in eradicating bacterial biofilms on titanium alloy in vitro. Biofilms of Staphylococcus aureus strains were grown on titanium alloy coupons for 24 h. Then, the coupons were taken to each treatment group: (i) debrided with PL, (ii) exposed to ultrasound, or (iii) exposed to both. An untreated biofilm was set as a control group. Viable plate count and confocal microscopy using live/dead staining was used to measure the amount of biofilm. Viable plate count showed an approximate two-log reduction in CFU/cm2 in PL alone, from an initial cell count on the mental surface of approximately 109 CFU/cm2. The ultrasound caused an approximate seven-log reduction, and the combination group eradicated viable biofilm bacteria completely. Confocal imaging corroborated the CFU data. Our results indicate that PL and ultrasound both are remarkably in eradicating biofilm, and the combination of PL and ultrasound is more effective than alone in reducing biofilm.

tpo3 and dur3, Aspergillus fumigatus Plasma Membrane Regulators of Polyamines, Regulate Polyamine Homeostasis and Susceptibility to Itraconazole.

Aspergillus fumigatus is a well-known opportunistic pathogen that causes invasive aspergillosis (IA) infections, which have high mortality rates in immunosuppressed individuals. Long-term antifungal drug azole use in clinical treatment and agriculture results in loss of efficacy or drug resistance. Drug resistance is related to cellular metabolites and the corresponding gene transcription. In this study, through untargeted metabolomics and transcriptomics under itraconazole (ITC) treatment, we identified two plasma membrane-localized polyamine regulators tpo3 and dur3, which were important for polyamine homeostasis and susceptibility to ITC in A. fumigatus. In the absence of tpo3 and/or dur3, the levels of cytoplasmic polyamines had a moderate increase, which enhanced the tolerance of A. fumigatus to ITC. In comparison, overexpression of tpo3 or dur3 induced a drastic increase in polyamines, which increased the sensitivity of A. fumigatus to ITC. Further analysis revealed that polyamines concentration-dependently affected the susceptibility of A. fumigatus to ITC by scavenging reactive oxygen species (ROS) at a moderate concentration and promoting the production of ROS at a high concentration rather than regulating drug transport. Moreover, inhibition of polyamine biosynthesis reduced the intracellular polyamine content, resulted in accumulation of ROS and enhanced the antifungal activity of ITC. Interestingly, A. fumigatus produces much lower levels of ROS under voriconazole (VOC) treatment than under ITC-treatment. Accordingly, our study established the link among the polyamine regulators tpo3 and dur3, polyamine homeostasis, ROS content, and ITC susceptibility in A. fumigatus.