TNFRSF6 induces mitochondrial dysfunction and microglia activation in the in vivo and in vitro models of sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis. The tumour necrosis factor receptor superfamily member 6 (TNFRSF6) gene encodes the Fas protein, and it participates in apoptosis induced in different cell types. This study aimed to explore TNFRSF6 function in SAE. The SAE mouse model was established by intraperitoneal injection of LPS in TNFRSF6-/- mice and C57BL/6J mice. Microglia were treated with LPS to establish the cell model. The learning, memory and cognitive functions in mice were tested by behavioral tests. Nissl staining was utilized for determining neuronal injury. Microglial activation was tested by immunofluorescence assay. ELISA was utilized for determining TNF-α, IL-1ß, IL-6, and IL-10 contents. Mitochondrial dysfunction was measured by mitochondrial oxygen consumption, ATP content, ROS production, and JC-1 assay. TNFRSF6 was upregulated in the LPS-induced mouse model and cell model. TNFRSF6 deficiency notably alleviated the impaired learning, memory and cognitive functions in SAE mice. Furthermore, we found that TNFRSF6 deficiency could alleviate neuronal injury, microglial activation, and inflammation in SAE mice. Additionally, mitochondrial dysfunction in the SAE mice was improved by TNFRSF6 depletion. In the LPS-induced microglia, we also proved that TNFRSF6 knockdown reduced inflammatory response inhibited ROS production, and alleviated mitochondrial dysfunction. TNFRSF6 induced mitochondrial dysfunction and microglia activation in the in vivo and in vitro models of SAE.

The trends in death of primary liver cancer caused by specific etiologies worldwide: results from the Global Burden of Disease Study 2019 and implications for liver cancer management.

BACKGROUND: Over past decades, epidemiological patterns of liver cancer (LC) have changed dramatically. The Global Burden of Disease (GBD) study provides an opportunity for tracking the progress in cancer control with its annual updated reports at national, regional and global level, which can facilitate the health decision-making and the allocation of health resources. Therefore, we aim to estimate the global, regional and national trends of death caused by liver cancer due to specific etiologies and attributable risks from 1990 to 2019. MATERIALS AND METHODS: Data was collected from the GBD study 2019. Estimated annual percentage changes (EAPC) were used to quantify the trends of age-standardized death rate (ASDR). We applied a linear regression for the calculation of estimated annual percentage change in ASDR. RESULTS: From 1990 to 2019, the ASDR of liver cancer decreased globally (EAPC = - 2.23, 95% confidence interval [CI]: - 2.61 to - 1.84). Meanwhile, declining trends were observed in both sexes, socio-demographic index (SDI) areas, and geographies, particularly East Asia (EAPC = - 4.98, 95% CI: - 5.73 to - 4.22). The ASDR for each of the four major etiologies fell globally, while liver cancer caused by hepatitis B had the largest drop (EPAC = - 3.46, 95% CI: - 4.01 to - 2.89). China has had dramatic decreases in death rates on a national scale, particularly when it comes to the hepatitis B etiology (EAPC = - 5.17, 95% CI: - 5.96 to - 4.37). However, certain nations, such as Armenia and Uzbekistan, saw a rise in liver cancer mortality. Controlling smoking, alcohol, and drug use contributed to a drop in LC-related mortality in the majority of socio-demographic index areas. Nevertheless, the excessive body mass index (BMI) was portrayed as the underlying cause for LC fatalities. CONCLUSION: From 1990 to 2019, there was a worldwide decrease in deaths caused by liver cancer and its underlying causes. However, rising tendencies have been observed in low-resource regions and countries. The trends in drug use- and high BMI-related death from liver cancer and its underlying etiologies were concerning. The findings indicated that efforts should be increased to prevent liver cancer deaths through improved etiology control and risk management.

Integrated bioinformatic analysis reveals NOS2 as a novel ferroptosis-related biomarker for pre-eclampsia.

BACKGROUND: Pre-eclampsia (PE) is a common condition in pregnancy; however, methods for early diagnosis and effective treatment options are lacking. Ferroptosis is a newly identified iron-dependent cell death pathway. The aim of this study was to investigate the role of ferroptosis-related genes in PE, the underlying mechanism, and their potential diagnostic value using a bioinformatics approach. METHODS: We downloaded the GSE48424 and GSE98224 datasets from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between PE and healthy pregnancy samples were identified in the GSE48424 dataset and subjected to weighted gene co-expression network analysis; the most relevant modules were intersected with known ferroptosis-related genes to distinctly identify the role of ferroptosis in PE. We further searched transcription factors and microRNAs that are predicted to regulate these ferroptosis-related genes, and patients in the GSE48424 dataset were divided into two groups according to high or low expression of the key ferroptosis-related genes associated with PE. To obtain robust key ferroptosis-related genes in PE, we validated their expression levels in the external dataset GSE98224. Finally, the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was utilized to access the expression of these genes in the PE and normal blood samples. RESULTS: Six ferroptosis-related genes involved in PE were obtained by overlapping 3661 genes most associated with PE, 565 DEGs between PE and normal samples, and 259 known ferroptosis-related genes. Among these genes, patients with PE displaying lower expression levels of NOS2 and higher expression levels of PTGS2 had a higher ferroptosis potential index. The expression pattern of NOS2 was consistent in the GSE48424 and GSE98224 datasets. RT-qPCR data confirmed that NOS2 expression was more significantly elevated in patients with PE than in those with a normal pregnancy. CONCLUSIONS: Our study explored the diagnostic value of ferroptosis-related genes in PE, and identified NOS2 as the key gene linking ferroptosis and PE, suggesting a new candidate biomarker for early PE diagnosis.

Global and national trends in years of life lost and years lived with disability caused by three common gastrointestinal cancers from 1990 to 2019.

BACKGROUND: Gastrointestinal cancers are a critical global cancer burden, and tracking their trends would inform the health policies. METHODS: Trends of years of life lost (YLLs) and years lived with disability (YLDs) caused by three common gastrointestinal cancers were estimated using annual percentage change (EAPC) and age-standardized rate (ASR). Data was extracted from the Global Burden of Disease study 2019. RESULTS: The ASR per 100,000 population-year of YLLs caused by esophageal cancer, stomach cancer, and colorectal cancer were 137.98, 264.15, and 282.51 in 2019, respectively. Their overall trends of YLLs declined during 1990-2019, with the respective EAPCs being - 1.42 (95% Confidence Interval [CI]: - 1.71 to - 1.13), - 2.13 (95%CI: - 2.29 to - 1.96), and - 0.25 (95%CI: - 0.30 to - 0.19). Meanwhile, decreasing trends of YLDs caused by esophageal cancer and stomach cancer were observed, in which the EAPCs were - 0.67 (95%: - 0.94 to - 0.40) and - 0.85 (95%CI: - 0.97 to - 0.73), respectively. However, an increasing trend was seen in that of colorectal cancer (EAPC = 0.83, 95%CI: 0.77 to 0.89). Among countries, the largest decrease in trend of YLLs was that of stomacher cancer in the Republic of Korea (EAPC = - 5.88, 95%CI: - 6.07 to - 5.69). However, pronounced increasing trend of YLDs caused by colorectal cancer occurred in China (EAPC = 4.40, 95%CI: 4.07 to 4.72). CONCLUSIONS: Decreasing trends in YLLs and YLDs caused by esophageal cancer, stomach cancer, and colorectal cancer were observed in most countries and regions, indicating that the great progress had been achieved over the past decades. However, the cancer burden was geographical heterogeneity, and cost-effective measures were still required to decline the burden caused by gastrointestinal cancers.

Global trends in incidence and death of neonatal disorders and its specific causes in 204 countries/territories during 1990-2019.

BACKGROUND: Neonatal disorders (ND) are a significant global health issue. This article aimed to track the global trends of neonatal disorders in 204 countries/territories from 1990 to 2019. METHODS: Data was explored from the Global Burden of Disease study 2019. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were calculated to quantify the trends of neonatal disorders and their specific causes, mainly included neonatal preterm birth (NPB), neonatal encephalopathy due to birth asphyxia and trauma (NE), neonatal sepsis and other neonatal infections (NS), and hemolytic disease and other neonatal jaundice (HD). RESULTS: In 2019, there were 23,532.23 × 103 incident cases of ND, and caused 1882.44 × 103 death worldwide. During 1990-2019, trends in the overall age-standardized incidence rate (ASIR) of ND was relatively stable, but that of age-standardized death rate (ASDR) declined (EAPC = -1.51, 95% confidence interval [CI]: -1.66 to -1.36). Meanwhile, decreasing trends of ASDR were observed in most regions and countries, particularly Cook Islands and Estonia, in which the respective EAPCs were -9.04 (95%CI: -9.69 to -8.38) and -8.12 (95%CI: -8.46 to -7.77). Among the specific four causes, only the NPB showed decreasing trends in the ASIR globally (EAPC = -0.19, 95%CI: -0.26 to -0.11). Decreasing trends of ASDR caused by ND underlying specific causes were observed in most regions, particularly the HD in Armenia, with the EAPC was -13.08 (95%CI: -14.04 to -12.11). CONCLUSIONS: Decreasing trends of death caused by neonatal disorders were observed worldwide from 1990 to 2019. However, the burden of neonatal disorders is still a considerable challenge, especially in low-resource settings, which need more effective health strategies.

Hierarchical Surface Inspired by Geminized Cationic Amphiphilic Polymer Brushes for Super-Antibacterial and Self-Cleaning Properties.

Pathogenic bacteria adhesion and formation of biofilm on the implant are the most common reasons for healthcare-associated device failure. Cationic amphiphilic polymer brushes containing covalently linked quaternary ammonium salts (QASs) are considered to be the most promising bactericidal materials, but these surfaces still suffer from incomplete bactericidal ability and serious microorganism accumulation. With this in mind, a novel kind of hierarchical surface integrating both geminized cationic amphiphilic antibacterial upper layer and zwitterionic antifouling sublayer has been developed in this study. Measurements of X-ray photoelectron spectroscopy, spectroscopic ellipsometry, atomic force microscopy, water contact angle, and surface ζ-potential were performed to investigate the surface functionalization process. The thicknesses and grafting densities of the pAGC8 upper blocks have been optimized to avert the mutual interference among different components. The optimal hierarchical surface exhibits an ultrahigh antibacterial activity and a potent self-cleaning functionality against both Staphylococcus aureus and Escherichia coli bacteria, as well as a certain protein repellence ability. Such a novel hierarchical architecture provides innovative guidance for the construction of super-antibacterial and self-cleaning brushes in many biomedical applications.

Direct Evidence of Salinity and pH Effects on the Interfacial Interactions of Asphaltene-Brine-Silica Systems.

The hydraulic fracturing technique remains essential to unlock fossil fuel from shale oil reservoirs. However, water imbibed by shale during hydraulic fracturing triggers environmental and technical challenges due to the low flowback water recovery. While it appears that the imbibition of fracturing fluid is a complex function of physico-chemical processes in particular capillary force which is associated with wettability of oil-brine-shale, the controlling factor(s) to govern the wettability is incomplete and the literature data in this context is missing. We thus measured the adsorption/desorption of asphaltenes on silica surface in the presence of brines using quartz crystal microbalance with dissipation (QCM-D). We detected zeta potential of asphaltene-brine and brine-silica systems and calculated the disjoining pressures of the asphaltene-brine-silica system in the case of different salinity. Moreover, we performed a geochemical study to quantify the variation of surface chemical species at asphaltene and silica surfaces with different pH values and used the chemical force microscope (CFM) method to quantify the effect of pH on intermolecular forces. Our results show that lowering salinity or raising pH reduced the adhesion force between asphaltene and silica surface. For example, at a pH value of 6.5, when the concentration of injected water is reduced from 1000 mM to 100 mM and 10 mM, the adhesion force decreased by approximately 58% and 66%, respectively. In addition, for the 100 mM NaCl solution, when the pH value increased from 4.5 to 6.5 and 9, the adhesion force decreased by approximately 56% and 87%, respectively. Decreased adhesion forces between asphaltene and the silica surface could promote the desorption of asphaltene from the silica surface, resulting in a negative zeta potential for both asphaltene-silica and brine-silica interfaces and a shift of wettability towards water-wet characteristic. During such a process, -NH+ number at asphaltene surfaces decreases and the bonds between -NH+ and >SiO- break down, to further interpret the formation of a thinner asphaltene adlayer on the rock surface. This study proposes a reliable theoretical basis for the application of hydraulic fracturing technology, and a facile and possible manipulation strategy to increase flowback water from unconventional reservoirs.

Ultrahighly Charged Amphiphilic Polymer Brushes with Super-Antibacterial and Self-Cleaning Capabilities.

Bacterial infection on biomaterial devices and the subsequent medical risks pose a serious problem in both human healthcare and industrial applications, resulting in a prevalence of various antimicrobial materials. Cationic amphiphilic polymer has been proposed to be a new generation of efficient antibacterial material, but the surface modified by such types of polymers still shows incomplete bactericidal ability and easily contaminated performance. With this in mind, a novel kind of geminized cationic amphiphilic polymer brush surface has been developed in this study, presenting a complete antibacterial activity, because of the synergistic biocidal effect of electrostatic and hydrophobic interactions, as well as the minimized contact area between bacteria and polymer surface. A structure self-adjustment process of polymer brush construction has been proposed, in which the mutual interference among cationic head groups can be avoided and the electrostatic repulsion and hydrophobic attraction can be balanced, in the formation of a smooth and tight surface. A self-cleaning capability of polymer surface has been performed via hydrolysis and degradation, maintaining a high antibacterial activity. Therefore, we provide a facile and possible manipulation strategy to fabricate super-antibacterial and self-cleaning surfaces in a wide range of biomedical and industrial applications.

Self-Assembly Behavior of Ultrahighly Charged Amphiphilic Polyelectrolyte on Solid Surfaces.

The adsorption process of a geminized amphiphilic polyelectrolyte, comprising double elementary charges and double hydrophobic tails in each repeat unit (denoted as PAGC8), was investigated and characterized by means of quartz crystal microbalance with dissipation (QCM-D), ellipsometry, and atomic force microscopy (AFM). By comparison, the self-assembly behaviors of a traditional polyelectrolyte without hydrophobic chains (denoted as PASC1) and an amphiphilic polyelectrolyte with a single hydrophilic headgroup and hydrophobic tail in each repeat unit (denoted as PASC8) at the solid/liquid interface were also investigated in parallel. A two-regime buildup was found in both amphiphilic systems of PASC8 and PAGC8, where the first regime was dependent on electrostatic interactions between polyelectrolytes and oppositely charged substrates, and the rearrangements of the preadsorbed chains and their aggregation behaviors on surface dominated the second regime. Furthermore, it was found that the adsorbed amount and conformation changed as a function of the charge density and bulk concentrations of the polyelectrolytes. The comparison of the adsorbed mass obtained from QCM-D and ellipsometry allowed calculating the coupling water content which reached high values and indicated a flexible aggregate conformation in the presence of PAGC8, resulting in controlling the suspension stability even at an extremely low concentration. In order to provide an insight into the mechanism of the suspension stability of colloidal dispersions, we gave a further explanation with respect to the interactions between surfaces in the presence of the geminized polyelectrolyte.

Antibacterial Activity of Geminized Amphiphilic Cationic Homopolymers.

The current study is aimed at investigating the effect of cationic charge density and hydrophobicity on the antibacterial and hemolytic activities. Two kinds of cationic surfmers, containing single or double hydrophobic tails (octyl chains or benzyl groups), and the corresponding homopolymers were synthesized. The antimicrobial activity of these candidate antibacterials was studied by microbial growth inhibition assays against Escherichia coli, and hemolysis activity was carried out using human red blood cells. It was interestingly found that the homopolymers were much more effective in antibacterial property than their corresponding monomers. Furthermore, the geminized homopolymers had significantly higher antibacterial activity than that of their counterparts but with single amphiphilic side chains in each repeated unit. Geminized homopolymers, with high positive charge density and moderate hydrophobicity (such as benzyl groups), combine both advantages of efficient antibacterial property and prominently high selectivity. To further explain the antibacterial performance of the novel polymer series, the molecular interaction mechanism is proposed according to experimental data which shows that these specimens are likely to kill microbes by disrupting bacterial membranes, leading them unlikely to induce resistance.

Minimally invasive removal of lumbar intradural extramedullary lesions using the interlaminar approach.

OBJECT Posterior midline laminectomy or hemilaminectomy has been successfully applied as the standard microsurgical technique for the treatment of spinal intradural pathologies. However, the associated risks of postoperative spinal instability increase the need for subsequent fusion surgery to prevent potential long-term spinal deformity. Continuous efforts have been made to minimize injuries to the surrounding tissue resulting from surgical manipulations. The authors report here their experiences with a novel minimally invasive surgical approach, namely the interlaminar approach, for the treatment of lumbar intraspinal tumors. METHODS A retrospective review was conducted of patients at the Second Affiliated Hospital of Zhejiang University School of Medicine who underwent minimally invasive resection of lumbar intradural-extramedullary tumors. By using an operative microscope, in addition to an endoscope when necessary, the authors were able to treat all patients with a unilateral, paramedian, bone-sparing interlaminar technique. Data including preoperative neurological status, tumor location, size, pathological diagnosis, extension of resections, intraoperative blood loss, length of hospital stay, and clinical outcomes were obtained through clinical and radiological examinations. RESULTS Eighteen patients diagnosed with lumbar intradural-extramedullary tumors were treated from October 2013 to March 2015 by this interlaminar technique. A microscope was used in 15 cases, and the remaining 3 cases were treated using a microscope as well as an endoscope. There were 14 schwannomas, 2 ependymomas, 1 epidermoid cyst, and 1 enterogenous cyst. Postoperative radiological follow-up revealed complete removal of all the lesions and no signs of bone defects in the lamina. At clinical follow-up, 14 of the 18 patients had less pain, and patients' motor/sensory functions improved or remained normal in all cases except 1. CONClUSIONS When meeting certain selection criteria, intradural-extramedullary lumbar tumors, especially schwannomas, can be completely and safely resected through a less-invasive interlaminar approach using a microscope, or a microscope in addition to an endoscope when necessary. This approach was advantageous because it caused even less bone destruction, resulting in better postoperative spinal stability, no need for facetectomy and fusion, and quicker functional recovery for the patients. Individualized surgical planning according to preoperative radiological findings is key to a successful microsurgical resection of these lesions through the interlaminar space.

[The mechanisms of heparin-derived oligosaccharide on the inhibition of smooth muscle cells proliferation induced by platelet-derived growth factor].

In this study, the effect of heparin-derived oligosaccharide (HDO) on platelet-derived growth factor (PDGF) induced vascular smooth muscle cells (VSMCs) proliferation and the related signal transduction mechanisms were investigated. MTT assays were used to measure VSMCs proliferation. Cell cycle distribution was analyzed by flow cytometry. The level of key regulatory proteins in PKC, MAPK and Akt/PI3K pathways were determined by RT-PCR, Western blot and immunocytochemical methods. Meanwhile, mRNA expressions of some proto-oncogenes were assayed by RT-PCR method. Our data showed that HDO (0.01, 0.1 and 1 µmol · L(-1)) inhibited 30 ng · mL(-1) PDGF-induced VSMCs proliferation in a dose-dependent manner, blocked the G1/S transition and inhibited the level of key regulatory proteins and some proto-oncogenes (P < 0.05). The results showed that HDO may decrease the key regulatory proteins expression, hence suppress the transcription of proto-oncogene and G1/S transition, finally inhibiting VSMCs proliferation.

Interactions between colloidal particles in the presence of an ultrahighly charged amphiphilic polyelectrolyte.

A novel amphiphilic polyelectrolyte denoted as PAGC8 and a traditional amphiphilic polyelectrolyte denoted as PASC8 were prepared. PAGC8 consisted of gemini-type surfactant segment based on 1,3-bis (N,N-dimethyl-N-octylammonium)-2-propyl acrylate dibromide, while PASC8 incorporated acryloyloxyethyl-N,N-dimethyl-N-dodecylammonium bromide as single chain surfactant units within its repeat unit structure. Turbidity, stability, and zeta potential measurements were performed in the presence of PAGC8 and PASC8, respectively, to evaluate their effectiveness in inducing solid/liquid separations. It was found that the maximum transmittance was observed before the zeta potential values reached the isoelectric point, implying that not only charge neutralization but also charge-patch mechanism contributed to the separation process. Colloid probe atomic force microscopy technique was introduced to directly determine the interactions between surfaces in the presence of ultrahighly charged amphiphilic polyelectrolyte. On the basis of the AFM results, we have successfully interpreted the influence of the charge density of the polyelectrolytes on the phase stability. Electrostatic interaction played the dominant role in the flocculation processes, although both electrostatic interaction and hydrophobic effect provided contributions to the colloidal dispersions. The attractions upon surfaces approach in the case of PAGC8 were significantly larger than that of PASC8 due to the higher charge density. The strong peeling events upon retraction in the presence of PAGC8 implied that the hydrophobic effect was stronger than that of PASC8, which displayed the loose pulling events. A strong attraction was identified at shorter separation distances for both systems. However, these interactions cannot be successfully described by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of colloid stability due to the participation of charge-patch and strong hydrophobic effect. To account for the additional interactions, we proposed an extended DLVO empirical model to explain the non-DLVO forces in the systems. A reasonable physical model was also proposed to further describe the interactions between surfaces in the two amphiphilic polyelectrolyte systems.

Environmentally responsive polymeric materials: effect of the topological structure on self-assembly.

A novel amphiphilic homopolymer (PAGC8), containing two hydrophilic head groups and double hydrophobic tails in each repeat unit, has been prepared by solution polymerization and named as "a geminized amphiphilic homopolymer" in this paper, which is capable of self-assembling into various nanoobjects depending on the solution concentration and solvent properties. Characterization of the self-assembly behaviors was carried out by steady-state fluorescence, transmission electron microscopy and nuclear magnetic resonance techniques. Particular emphasis was dedicated to the environmental responsiveness of the assemblies. The morphologies were observed to transform from micelle-type to vesicles on adding a certain amount of ethanol. It is noteworthy that the assemblies were able to trap hydrophilic (rhodamine B) and hydrophobic (Sudan Red) molecules. Subsequently different nanoobjects were found after the encapsulation. To probe the effect of the topological structure on the self-assembly behaviors, the properties of an additional homopolymer with single charge pendant architecture on the backbone were investigated for comparison. Significant differences in structure between the two architectures brought out remarkable variations in aggregates, which were non-responsive to the solvent environment, or encapsulation of molecules. Based on the experimental results, we proposed a possible mechanism of the morphological transitions of the assemblies.

Evaluating high-flow oxygen therapy after mechanical thrombectomy under general anesthesia in acute ischemic stroke: A retrospective single-center study.

BACKGROUND: The use of mechanical thrombectomy for acute intracranial vascular occlusion under general anesthesia with endotracheal intubation is well-established as a safe and effective method. However, the process of extubation post-surgery presents challenges for certain patients. This retrospective study assesses the safety and efficacy of combining mechanical ventilation with high-flow oxygen inhalation as an interim strategy, while also examining its impact on long-term clinical outcomes. METHODS: This research enrolled 119 patients with acute intracranial large vessel occlusion who underwent mechanical thrombectomy under general anesthesia with tracheal intubation between January 2020 and November 2023. Participants were categorized into two groups: Group 1 (n=55), which received high-flow oxygen (HFO) post-extubation, and Group 2 (n=64), which was treated with routine oxygen supplementation (RO). The study compared reintubation and tracheotomy rates between these groups to determine safety and effectiveness. Additionally, it analyzed long-term clinical outcomes by comparing NIHSS and mRS scores before treatment and at 90-day follow-up. RESULTS: The reintubation rate post-extubation was significantly lower in the HFO group (12.7 %, n=7) compared to the RO group (31.2 %, n=20, p=0.016). The incidence of tracheotomy within 7 days was also reduced in the HFO group compared to the RO group (7.3 %, n=4 vs 20.3 %, n=13, p=0.043). Moreover, a greater proportion of patients in the HFO group achieved mRS scores of 0-2 at 90 days post-stroke than those in the RO group (60 %, n=33 vs 40.6 %, n=26, p=0.035). The median NIHSS score at 90 days was more favorable in the HFO group than in the RO group (6, IQR [1-18] vs 8, IQR [1-20], p=0.005). CONCLUSION: The study suggests that high-flow oxygen therapy after mechanical thrombectomy under general anesthesia with tracheal intubation may lessen the need for reintubation and tracheotomy, potentially leading to improved long-term prognosis.

Combining experiments and bioinformatics to identify transforming growth factor-ß1 as a key regulator in angiotensin II-induced trophoblast senescence.

INTRODUCTION: Accelerated senescence of trophoblast may cause several diverse pregnancy outcomes; however, the cause of accelerated trophoblast senescence remains unclear. The renin-angiotensin system (RAS) is closely related to organ senescence. Therefore, in the present study, we hypothesized that angiotensin (Ang)II, one of the most important RAS family members, accelerates trophoblast senescence through the transforming growth factor ß-1 (TGF-ß1) pathway. METHODS: AngII and Ang1-7 were used to stimulate pregnant rats. AngII and its inhibitor olmesartan were used to stimulate trophoblast. Thereafter, senescence levels were measured. Furthermore, we used AngII to stimulate trophoblast and utilized RNA-sequencing (RNAseq) to analyze the expression of differentially expressed genes (DEGs). After identifying the overlapping genes by comparing the DEGs and senescence-related genes, we employed CytoHubba software to calculate the top five hub genes and selected TGF-ß1 as the target gene. We transfected the AngII-stimulated trophoblast with TGF-ß1 small interfering RNA (siRNA) and measured the senescence levels. RESULTS: Senescence markers were upregulated in the AngII group compared with that in the control group. Furthermore, following AngII stimulation and RNAseq measurement, we identified 607 DEGs and 13 overlapping genes. The top five hub genes were as follows: PLAU, PTGS2, PDGF-ß, TGF-ß1, and FOXO3. Upon knockdown of TGF-ß1 expression in AngII-stimulated trophoblast using TGF-ß1 siRNA, we observed a downregulation of p53 and p62 mRNA expression. DISCUSSION: AngII accelerates trophoblast senescence through the TGF-ß1 pathway.

Declined Serum Resolvin D1 Levels to Predict Severity and Prognosis of Human Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

Background: Resolvin D1 (RvD1) possesses anti-inflammatory properties and may be neuroprotective. This study was designed to ascertain the potential role of serum RvD1 in the evaluation of aSAH severity and prognosis of human aneurysmal subarachnoid hemorrhage (aSAH). Methods: In this prospective observational study, serum RvD1 levels were measured in 123 patients with aSAH and in 123 healthy volunteers. Six-month neurological function was assessed using extended Glasgow outcome scale (GOSE). A prognostic prediction model was appraised using a series of evaluative tools, such as a nomogram, receiver operating characteristic (ROC) curve, decision curve, calibration curve, restricted cubic spline, and Hosmer-Lemeshow goodness of fit statistics. Results: Serum RvD1 levels were markedly lower in patients than in controls (median, 0.54 versus 1.47 ng/mL; P<0.001). Serum RvD1 levels were independently correlated with Hunt-Hess scores (beta, -0.154; 95% confidence interval [CI], -0.198--0.109; VIF, 1.769; P=0.001), modified Fisher scores (beta, -0.066; 95% CI, -0.125--0.006; VIF, 1.567; P=0.031) and 6-month GOSE scores (beta, 1.864; 95% CI, 0.759-2.970; VIF, 1.911; P=0.001) and were independently predictive of a poor prognosis (GOSE scores of 1-4) (odds ratio, 0.137; 95% CI, 0.023-0.817; P=0.029). Serum RvD1 levels significantly distinguished the risk of a worse prognosis, with an area under the ROC curve of 0.750 (95% CI, 0.664-0.824). Using the Youden method, serum RvD1 levels < 0.6 ng/mL was effective in predicting worse prognosis with 84.1% sensitivity and 62.0% specificity. Moreover, the model containing serum RvD1 levels, Hunt-Hess scores and modified Fisher scores was efficient, reliable and beneficial in prognostic prediction using a series of the afore-mentioned evaluative tools. Conclusion: A decline in serum RvD1 levels following aSAH is closely correlated with illness severity and independently predicts a worse outcome in patients with aSAH, implying that serum RvD1, as a prognostic biomarker of aSAH, may be of clinical value in aSAH.

Investigating the molecular mechanism of traditional Chinese medicine for the treatment of placental syndromes by influencing inflammatory cytokines using the Mendelian randomization and molecular docking technology.

Introduction: Placental syndromes, which include pregnancy loss, preterm birth, gestational diabetes mellitus (GDM), and hypertensive disorders in pregnancy (HDP), have a strong association with disorder inflammatory reactions. Nonetheless, the exact causal relationship has not been established. This study aims to investigate the causal relationship between placental syndromes and inflammatory cytokines utilizing Mendelian randomization (MR). Additionally, we examined the interaction between small molecular compounds derived from traditional Chinese medicine and inflammatory cytokines using molecular docking method. Methods: After obtaining the data of inflammatory cytokines and placental syndromes, as well as establishing single nucleotide polymorphisms (SNPs), we employed the inverse variance weighted (IVW) method to assess the causal relationship. We also accessed the heterogeneity and the horizontal pleiotropy of these data. The "ClusterProfiler" R package was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term analyses. The protein-protein interaction (PPI) network was constructed using STRING database. AutoDock Vina software was used for molecular docking, and Discovery Studio 2019 was used for visualization purposes. Results: We found that the growth regulated oncogene A (GROA) and interleukin-9 (IL-9) were associated with the development of pregnancy hypertension, whereas interleukin-10 (IL-10) and hepatocyte growth factor (HGF) were linked to the occurrence of preeclampsia. Moreover, there were correlations observed between interleukin-18 (IL-18), IL-10, macrophage colony-stimulating factor (MCSF), and platelet-derived growth factor BB (PDGFbb) in cases of chronic hypertension combined with pregnancy (CHP). Additionally, macrophage migration inhibitory factor (MIF) exhibited a connection with GDM, and TNF related apoptosis inducing ligand (TRAIL) demonstrated a causal relationship with preterm birth. It is plausible to suggest that interleukin-1ß (IL-1ß) might contribute to the promotion of pregnancy loss. All of the binding free energy values of small molecular compounds with inflammatory cytokines were below -5.0 kcal/mol. Furthermore, all of the RMSD values were less than 2. Conclusions: GROA, IL-1ß, IL-9, IL-10, IL-18, MIF, MCSF, HGF, PDGFbb and TRAIL were found to be causally associated with placental syndromes. Molecular docking analysis revealed that small molecular compounds, such as puerarin, magnolol, atractylenolide I, paeoniflorin, tumulosic acid and wogonin, are closely bound to these inflammatory cytokines.

Spatial and Temporal Trends in HIV/AIDS Burden Among Worldwide Regions From 1990 to 2019: A Secondary Analysis of the Global Burden of Disease Study 2019.

Purpose: HIV/AIDS is a critical public health concern worldwide. This article investigated the spatial and temporal trends in HIV/AIDS burden from 1990 to 2019. Methods: Data were extracted from the Global Burden of Disease (GBD) Study 2019. The estimated annual percentage change (EAPC) and the age-standardized rate (ASR) were used to quantify the change in trends at the global, regional, and national levels. Results: In terms of temporal trends, during the period 1990-2004, increasing trends in prevalence (EAPC = 7.47, 95% confidence interval [CI] 5.84, 9.12), death (EAPC = 10.85, 95% CI 8.90-12.84), and disability-adjusted life years (DALYs) (EAPC = 10.40, 95% CI 8.47-12.36) of HIV/AIDS were observed. During the period 2005-2019, the global trends in HIV/AIDS incidence, death, and DALYs of HIV/AIDS decreased, with the EAPCs of -2.68 (95% CI-2.82--2.53), -6.73 (95% CI -6.98--6.47), and -6.75 (95% CI -6.95--6.54), respectively. However, the disease prevalence showed a slight increasing trend (EAPC = 0.71, 95% CI 0.54-0.87). In terms of spatial trends, over the past 15 years, trends in HIV/AIDS incidence of HIV/AIDS appeared upward in High-middle and High sociodemographic index (SDI) areas (EAPC = 6.51, 95% CI 5.50-7.53; EAPC = 2.31, 95% CI 2.02-2.60, respectively). Conclusion: Decreasing trends in HIV/AIDS incidence, death, and DALYs have been observed worldwide over the past 15 years, especially in death and DALYs rates. However, the global population living with HIV/AIDS is still increasing. It is worth noting that an unfavorable trend emerged in High-middle and High SDI areas. Prevention and control of HIV/AIDS still need to be strengthened to counteract these concerning trends.

Global burden of rheumatic heart disease: trends from 1990 to 2019.

BACKGROUND: Rheumatic heart disease (RHD) is a critical public health issue worldwide, and its epidemiological patterns have changed over the decades. This article aimed to estimate the global trends of RHD, and attributable risks from 1990 to 2019. METHODS: Data on RHD burden were explored from the Global Burden of Disease Study 2019. Trends of the RHD burden were estimated using the estimated annual percentage change (EAPC) and age-standardized rate (ASR). RESULTS: During 1990-2019, increasing trends in the ASR of incidence and prevalence of RHD were observed worldwide, with the respective EAPCs of 0.58 (95% confidence interval [CI] 0.52 to 0.63) and 0.57 (95%CI 0.50 to 0.63). Meanwhile, increasing trends commonly occurred in low and middle Socio-Demographic Index (SDI) regions and countries. The largest increasing trends in the ASR of incidence and prevalence were seen in Fiji, with the respective EAPCs being 2.17 (95%CI 1.48 to 2.86) and 2.22 (95%CI 1.53 to 2.91). However, death and disability-adjusted life years (DALYs) due to RHD showed pronounced decreasing trends of ASR globally, in which the EAPCs were - 2.98 (95%CI - 3.03 to - 2.94) and - 2.70 (95%CI - 2.75 to - 2.65), respectively. Meanwhile, decreasing trends were also observed in all SDI areas and geographic regions. The largest decreasing trends of death were observed in Thailand (EAPC = - 9.55, 95%CI - 10.48 to - 8.61). Among the attributable risks, behavioral risk-related death and DALYs caused by RHD had pronounced decreasing trends worldwide and in SDI areas. CONCLUSIONS: Pronounced decreasing trends of death and DALYs caused by RHD were observed in regions and countries from 1990 to 2019, but the RHD burden remains a substantial challenge globally. The results would inform the strategies for more effective prevention and control of RHD.