Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA‐induced ...ALI (SA‐ALI) remains unclear. In this study, serum samples were collected from SA‐sepsis patients, and a SA‐ALI mouse model was established by grouping WT and Nrf2−/− mice after 6 h of intraperitoneal injection. A cell model simulating SA‐ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA‐sepsis patients, negatively correlated with the severity of ALI. In SA‐ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation‐induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA‐ALI. The p‐Nrf2/total‐Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA‐treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual‐luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA‐ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.
In this study, the authors investigated that activation of the Nrf2/PHB2 pathway in alveolar epithelial type II cells (AT II) can alleviate mitochondrial damage caused by Staphylococcus aureus‐induced sepsis in mice, thereby promoting the survival of AT II and preventing progression to acute lung injury. Nrf2 plays a key role in the mitochondrial retention of PHB2, and its nuclear translocation can increase the expression of PHB2 to prevents mitochondrial dysfunction
.
Heightened sympathetic nerve activity is associated with occurrence of ventricular arrhythmia (VA).
To investigate the association of skin sympathetic nerve activity (SKNA) and VA occurrence.
We ...prospectively enrolled 65 patients with severe cardiomyopathy. Of these, 39 had recent sustained VA episodes (VA-1 group), 11 had intractable VA undergoing sedation with general anesthesia (VA-2 group), and 15 had no known history of VA (VA-Ctrl group). All patients had simultaneous SKNA and electrocardiogram recording. SKNA was assessed using an average value (aSKNA), a variable value (vSKNA), and the number of bursts of SKNA (bSKNA).
The VA-1 group had higher aSKNA and vSKNA compared with the VA-Ctrl group (aSKNA: 1.41 ± 0.53 μV vs 0.98 ± 0.41 μV, P = .003; vSKNA: 0.52 ± 0.22 μV vs 0.30 ± 0.16 μV, P < .001) and the VA-2 group (aSKNA: 0.83 ± 0.22 μV, P < .001; vSKNA: 0.23 ± 0.11 μV; P < .001). Although the VA-2 group had more VA episodes than the VA-1 group (median, 5 vs 2; P = .01), their SKNA was the lowest among the 3 groups. Multivariate Cox regression analysis showed that a higher aSKNA at baseline was an independent predictor of lower VA recurrence rate during a 417 ± 279-day follow-up (hazard ratio, 0.325; 95% confidence interval CI, 0.119-0.883; P = .03). A >15% reduction in aSKNA after therapy was associated with a lower subsequent VA event rate (hazard ratio, 0.222; 95% CI, 0.057-0.864; P = .03).
Patients with VA had increased SKNA as compared with control. Both SKNA and sustained VA could be suppressed by general anesthesia. The aSKNA at baseline was an independent predictor of VA recurrence.
Accurate road information is important for applications involving road maintenance, intelligent transportation, and road network updates. Mobile laser scanning (MLS) can effectively extract road ...information. However, accurately extracting road edges based on large-scale data for complex road conditions, including both structural and non-structural road types, remains difficult. In this study, a robust method to automatically extract structural and non-structural road edges based on a topological network of laser points between adjacent scan lines and auxiliary surfaces is proposed. The extraction of road and curb points was achieved mainly from the roughness of the extracted surface, without considering traditional thresholds (e.g., height jump, slope, and density). Five large-scale road datasets, containing different types of road curbs and complex road scenes, were used to evaluate the practicality, stability, and validity of the proposed method via qualitative and quantitative analyses. Measured values of the correctness, completeness, and quality of extracted road edges were over 95.5%, 91.7%, and 90.9%, respectively. These results confirm that the proposed method can extract road edges from large-scale MLS datasets without the need for auxiliary information on intensity, image, or geographic data. The proposed method is effective regardless of whether the road width is fixed, the road is regular, and the existence of pedestrians and vehicles. Most importantly, the proposed method provides a valuable solution for road edge extraction that is useful for road authorities when developing intelligent transportation systems, such as those required by self-driving vehicles.
Purpose
This prospective study was performed to investigate long-term (8-year) survival in patients with solitary large hepatocellular carcinoma (HCC) ranging from 5 to 7 cm who underwent ...transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) and identify factors that significantly affected outcomes.
Methods
Forty-eight patients with large HCC (36 men, 12 women; mean age, 57.0 ± 11.2 range, 37–82 years) without fever or signs of infection were enrolled. All patients were treated with TACE + RFA. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan–Meier method. Prognostic factors were assessed using the Cox hazards regression method.
Results
The median OS duration was 47.0 months, and the 1-, 3-, 5-, and 8-year OS rates were 73%, 57%, 53%, and 27%, respectively. The median DFS duration was 9.05 (3.99–12.01) months, and the 1-, 3-, and 5-year DFS rates were 35%, 9%, and 0%, respectively. Cox hazards regression analysis revealed that the Child–Pugh class, platelet count, lymphocyte-to-monocyte ratio (LMR), and DFS were independent predictive factors of OS (
p
= 0.000, 0.003, 0.020, and 0.000, respectively). The LMR and platelet-to-lymphocyte ratio (PLR) were independent predictive factors of recurrence (
p
= 0.046 and 0.016, respectively).
Conclusion
TACE + RFA may be a safe and effective treatment for selected solitary large HCC ranging from 5 to 7 cm. Measurement of the LMR (> 4) and PLR (≤ 100) in peripheral blood before the intervention might help to identify which patients with solitary large HCC are suitable for TACE + RFA.
Registration number:
ChiCTR-TRC-12002768 (
https://www.chictr.org.cn
).
Due to its high electrochemical activities and low intercalation potential for Li/Li+, transition metal phosphides (TMPs) are booming as commerciogenic anode for lithium‐ion batteries (LIBs). Herein, ...the reasonable devise of nitrogen‐doped carbon‐coated CoP (CoP@NC) nanocomposites, which is derived from metal–organic frameworks (MOF‐Co) precursors, combining with graphene modification, is presented. The ultrafine CoP@NC nanoparticles are strongly incorporated with graphene networks (CoP@NC/GO). When assessed as anode electrode for LIBs, novel dual carbon encapsulation architectures of CoP@NC/GO hybrid composites exhibit superior cyclability (345 mAh g−1 at 1500 mA g−1 after 1000 cycles) and prominent rate ability (404 mAh g−1 at 3000 mA g−1). It is believed that this strategy can be helpful for boosting the electrochemical performance of the TMPs family as advance anode materials for energy storage systems.
CoP nanoparticles are synthesized using metal–organic frameworks‐Co as templates. The CoP nanoparticles coated with N‐doped carbon are homogeneously embedded into the graphene network which can effectively provide highly efficient pathways for electrons/ions and buffer the volume expansion. The hybrid electrode delivers a high reversible capacity at a high current density of 1500 mA h g−1.
DNA binding inhibitory factor 3 (ID3) has been shown to have a key role in maintaining proliferation and differentiation. It has been suggested that ID3 may also affect mammalian ovarian function. ...However, the specific roles and mechanisms are unclear. In this study, the expression level of ID3 in cumulus cells (CCs) was inhibited by siRNA, and the downstream regulatory network of ID3 was uncovered by high-throughput sequencing. The effects of ID3 inhibition on mitochondrial function, progesterone synthesis, and oocyte maturation were further explored. The GO and KEGG analysis results showed that after ID3 inhibition, differentially expressed genes, including StAR, CYP11A1, and HSD3B1, were involved in cholesterol-related processes and progesterone-mediated oocyte maturation. Apoptosis in CC was increased, while the phosphorylation level of ERK1/2 was inhibited. During this process, mitochondrial dynamics and function were disrupted. In addition, the first polar body extrusion rate, ATP production and antioxidation capacity were reduced, which suggested that ID3 inhibition led to poor oocyte maturation and quality. The results will provide a new basis for understanding the biological roles of ID3 as well as cumulus cells.
•Inhibition of ID3 reduces progesterone synthesis in bovine cumulus cells.•Inhibition of ID3 induces cumulus cell apoptosis.•Inhibition of ID3 affects mitochondrial dynamics in cumulus cells.•Inhibition of ID3 in cumulus cells reduces the quality of oocytes.
(1) Background: DNA double strand breaks (DSBs) are the most serious form of DNA damage that affects oocyte maturation and the physiological state of follicles and ovaries. Non-coding RNAs (ncRNAs) ...play a crucial role in DNA damage and repair. This study aims to analyze and establish the network of ncRNAs when DSB occurs and provide new ideas for next research on the mechanism of cumulus DSB. (2) Methods: Bovine cumulus cells (CCs) were treated with bleomycin (BLM) to construct a DSB model. We detected the changes of the cell cycle, cell viability, and apoptosis to determine the effect of DSBs on cell biology, and further evaluated the relationship between the transcriptome and competitive endogenous RNA (ceRNA) network and DSBs. (3) Results: BLM increased γH2AX positivity in CCs, disrupted the G1/S phase, and decreased cell viability. Totals of 848 mRNAs, 75 long noncoding RNAs (lncRNAs), 68 circular RNAs (circRNAs), and 71 microRNAs (miRNAs) in 78 groups of lncRNA-miRNA-mRNA regulatory networks, 275 groups of circRNA-miRNA-mRNA regulatory networks, and five groups of lncRNA/circRNA-miRNA-mRNA co-expression regulatory networks were related to DSBs. Most differentially expressed ncRNAs were annotated to cell cycle, p53, PI3K-AKT, and WNT signaling pathways. (4) Conclusions: The ceRNA network helps to understand the effects of DNA DSBs activation and remission on the biological function of CCs.
Background
T‐box transcription factor 2 (TBX2) is a member of T‐box gene family whose members are highly conserved in evolution and encoding genes and are involved in the regulation of developmental ...processes. The encoding genes play an important role in growth and development. Although TBX2 has been widely studied in cancer cell growth and development, its biological functions in bovine cumulus cells remain unclear.
Objectives
This study aimed to investigate the regulatory effects of TBX2 in bovine cumulus cells.
Methods
TBX2 gene was knockdown with siRNA to clarify the function in cellular physiological processes. Cell proliferation and cycle changes were determined by xCELLigence cell function analyzer and flow cytometry. Mitochondrial membrane potential and autophagy were detected by fluorescent dye staining and immunofluorescence techniques. Western blot and quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR) were used to detect the expression changes of proliferation and autophagy‐related proteins. Aadenosine triphosphate (ATP) production, glucose metabolism, and cholesterol synthesis of cumulus cells were measured by optical density and chemiluminescence analysis.
Results
After inhibition of TBX2, the cell cycle was disrupted. The levels of apoptosis, ratio of light chain 3 beta II/I, and reactive oxygen species were increased. The proliferation, expansion ability, ATP production, and the amount of cholesterol secreted by cumulus cells were significantly decreased.
Conclusions
TBX2 plays important roles in regulating the cells’ proliferation, expansion, apoptosis, and autophagy; maintaining the mitochondrial function and cholesterol generation of bovine cumulus cells.
TBX2 has regulatory roles in regulating the cells proliferation, expansion, apoptosis, autophagy, maintaining the mitochondrial function, and cholesterol generation of bovine cumulus cells.
Subcutaneous Nerve Activity
Introduction
We tested the hypothesis that subcutaneous nerve activity (SCNA) of the thorax correlates with the stellate ganglion nerve activity (SGNA) and can be used to ...estimate the sympathetic tone.
Methods and Results
We implanted radio transmitters in 11 ambulatory dogs to record left SGNA, left thoracic vagal nerve activity (VNA), and left thoracic SCNA, including 3 with simultaneous video monitoring and nerve recording. Two additional dogs were studied under general anesthesia with apamin injected into the right stellate ganglion while the right SGNA and the right SCNA were recorded. There was a significant positive correlation between integrated SGNA (iSGNA) and integrated SCNA (iSCNA) in the first 7 ambulatory dogs, with correlation coefficient of 0.70 (95% confidence interval CI 0.61–0.84, P < 0.05 for each dog). Tachycardia episodes (heart rate exceeding 150 bpm for ≥3 seconds) were invariably preceded by SGNA and SCNA. There was circadian variation of both SCNA and SGNA. Crosstalk was ruled out because SGNA, VNA, and SCNA bursts had different timing and activation patterns. In an eighth dog, closely spaced bipolar subcutaneous electrodes also recorded SCNA, but with reduced signal to noise ratio. Video monitoring in additional 3 dogs showed that movement was not a cause of high frequency SCNA. The right SGNA correlated strongly with right SCNA and heart rate in 2 anesthetized dogs after apamin injection into the right stellate ganglion.
Conclusions
SCNA recorded by bipolar subcutaneous electrodes correlates with the SGNA and can be used to estimate the sympathetic tone.
•rFSAV is a novel recombinant five-antigen Staphylococcus aureus vaccine.•Three immunization doses and four procedures were evaluated in phase 1a and 1b.•rFSAV is safe, well tolerated in healthy ...adults.•rFSAV elicits rapid and robust specific humoral and cellular immune responses.•Optimal perioperative regimen is worth further evaluation in targeted population.
Staphylococcus aureus is an important pathogen that causes hospital and community infections. To control Staphylococcus aureus infection and reduce the usage of antibiotics, we evaluated the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in healthy adults.
We conducted a randomized, double-blind, placebo-controlled phase 1a study and a randomized, open-label phase 1b study. In phase 1a, we randomly allocated 144 healthy participants in a ratio of 1:1:1:1 to receive the low-(60 μg), middle-(120 μg), and high-dose (240 μg) vaccine or placebo at day 0, 3, 7 and 14. In phase 1b, 144 healthy participants were randomly allocated at a ratio of 1:1:1:1 to receive 0–3–7, 0/0–7, 0/0–3–7, 0/0–7–14 regimens to estimate the optimal strategy. The primary study endpoint was the incidence of solicited adverse events post-vaccination. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as the cellular immune responses and functional antibodies.
There were 31 (86%), 30 (83%), and 32 (89%) of 36 participants in the low-, middle-, and high-dose group reported solicited adverse events, respectively, most of the adverse events were mild or moderate. In phase 1b, the dose-adjusted rFSAV (90 μg) showed a better safety profile in the four immune procedures, and no vaccine-related serious adverse events were reported. The antigen-specific binding antibodies started to increase at day 7 and reached the peak around day 14 to 21. The cellular immune responses and functional antibodies also were substantially above background levels.
rFSAV is safe, well tolerated in healthy adults, elicits rapid and robust specific humoral and cellular immune responses with unconventional immunization procedure in phase 1a and 1b. It deserves to be noted and further explored.
Clinical Trials Registration: NCT02804711 and NCT03966040.
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