Preparation and characterization of a polyurethane-based sponge wound dressing with a superhydrophobic layer and an antimicrobial adherent hydrogel layer.

Bacterial infection poses a significant impediment in wound healing, necessitating the development of dressings with intrinsic antimicrobial properties. In this study, a multilayered wound dressing (STPU@MTAI2/AM1) was reported, comprising a surface-superhydrophobic treated polyurethane (STPU) sponge scaffold coupled with an antimicrobial hydrogel. A superhydrophobic protective outer layer was established on the hydrophilic PU sponge through the application of fluorinated zinc oxide nanoparticles (F-ZnO NPs), thereby resistance to environmental contamination and bacterial invasion. The adhesive and antimicrobial inner layer was an attached hydrogel (MTAI2/AM1) synthesized through the copolymerization of N-[2-(methacryloyloxy)ethyl]-N, N, N-trimethylammonium iodide and acrylamide, exhibits potent adherence to dermal surfaces and broad-spectrum antimicrobial actions against resilient bacterial strains and biofilm formation. STPU@MTAI2/AM1 maintained breathability and flexibility, ensuring comfort and conformity to the wound site. Biocompatibility of the multilayered dressing was demonstrated through hemocompatibility and cytocompatibility studies. The multilayered wound dressing has demonstrated the ability to promote wound healing when addressing MRSA-infected wounds. The hydrogel layer demonstrates no secondary damage when peeled off compared to commercial polyurethane sponge dressing. The STPU@MTAI2/AM1-treated wounds were nearly completely healed by day 14, with an average wound area of 12.2 ± 4.3 %, significantly lower than other groups. Furthermore, the expression of CD31 was significantly higher in the STPU@MTAI2/AM1 group compared to other groups, promoting angiogenesis in the wound and thereby contributing to wound healing. Therefore, the prepared multilayered wound dressing presents a promising therapeutic candidate for the management of infected wounds. STATEMENT OF SIGNIFICANCE: Healing of chronic wounds requires avoidance of biofouling and bacterial infection. However developing a wound dressing which is both anti-biofouling and antimicrobial is a challenge. A multilayered wound dressing with multifunction was developed. Its outer layer was designed to be superhydrophobic and thus anti-biofouling, and its inner layer was broad-spectrum antimicrobial and could inhibit biofilm formation. The multilayered wound dressing with adhesive property could easily be removed from the wound surface preventing the cause of secondary damage. The multilayered wound dressing has demonstrated good abilities to promote MRSA-infected wound healing and presents a viable treatment for MRSA-infected wound.

Revealing the spatiotemporal brain dynamics of covert speech compared with overt speech: A simultaneous EEG-fMRI study.

Covert speech (CS) refers to speaking internally to oneself without producing any sound or movement. CS is involved in multiple cognitive functions and disorders. Reconstructing CS content by brain-computer interface (BCI) is also an emerging technique. However, it is still controversial whether CS is a truncated neural process of overt speech (OS) or involves independent patterns. Here, we performed a word-speaking experiment with simultaneous EEG-fMRI. It involved 32 participants, who generated words both overtly and covertly. By integrating spatial constraints from fMRI into EEG source localization, we precisely estimated the spatiotemporal dynamics of neural activity. During CS, EEG source activity was localized in three regions: the left precentral gyrus, the left supplementary motor area, and the left putamen. Although OS involved more brain regions with stronger activations, CS was characterized by an earlier event-locked activation in the left putamen (peak at 262 ms versus 1170 ms). The left putamen was also identified as the only hub node within the functional connectivity (FC) networks of both OS and CS, while showing weaker FC strength towards speech-related regions in the dominant hemisphere during CS. Path analysis revealed significant multivariate associations, indicating an indirect association between the earlier activation in the left putamen and CS, which was mediated by reduced FC towards speech-related regions. These findings revealed the specific spatiotemporal dynamics of CS, offering insights into CS mechanisms that are potentially relevant for future treatment of self-regulation deficits, speech disorders, and development of BCI speech applications.

Shell Modulation of Hollow Metal Sulfide Nanocomposite for Stable Potassium Storage at Room and High Temperature.

The large size of K-ion makes the pursuit of stable high-capacity anodes for K-ion batteries (KIBs) a formidable challenge, particularly for high temperature KIBs as the electrode instability becomes more aggravated with temperature climbing. Herein, we demonstrate that a hollow ZnS@C nanocomposite (h-ZnS@C) with a precise shell modulation can resist electrode disintegration to enable stable high-capacity potassium storage at room and high temperature. Based on a model electrode, we identify an interesting structure-function correlation of the h-ZnS@C: with an increase in the shell thickness, the cyclability increases while the rate and capacity decreases, shedding light on the design of high-performance h-ZnS@C anodes via engineering the shell thickness. Typically, the h-ZnS@C anode with a shell thickness of 60 nm can deliver an impressive comprehensive performance at room temperature; the h-ZnS@C with shell thickness increasing to 75 nm can achieve an extraordinary stability (88.6% capacity retention over 450 cycles) with a high capacity (450 mAh g-1) and a superb rate even at an extreme temperature of 60 ℃, which is much superior than those reported anodes. This contribution envisions new perspectives on rational design of functional metal sulfides composite toward high-performance KIBs with insights into the significant structure-function correlation.

Recycling drinking water treatment sludge in construction and building materials: A review.

Drinking water treatment sludge (DWTS) is a by-product of water treatment, and it is difficult to recycle to high value and poses potential environmental risks. Recycling DWTS into cement-based materials is an effective measure to achieve its high-volume utilization and reduce its environmental load. DWTS is rich in silica-alumina phases and has potential pozzolanic activity after drying, grinding and calcination, giving it similar properties to traditional supplementary cementitious materials. Adjusting the sludge production process and coagulant type will change its physical and chemical properties. Adding a small amount of DWTS can generate additional hydration products and refine the pore structure of the cement sample, thus improving the mechanical properties and durability of the sample. However, adding high-volume DWTS to concrete causes microstructural deterioration, but it is feasible to use high-volume DWTS to produce artificial aggregates, lightweight concrete, and sintered bricks. Meanwhile, calcined DWTS has similar compositions to clay, which makes it a potential raw material for cement clinker production. Cement-based materials can effectively solidify heavy metal ions in DWTS, and alkali-activated binders, magnesium-based cement, and carbon curing technology can further reduce the risk of heavy metal leaching. This review provides support for the high-value utilization of DWTS in cement-based materials and the reduction of its potential environmental risks.

Upcycling textile sludge into magnesium oxychloride cement: Physical properties, microstructure, and leaching behavior.

Textile sludge is a by-product produced during the wastewater treatment process in the textile printing and dyeing industry. Textile sludge is rich in heavy metal elements, which makes it a potential risk to the surrounding environment. This study designs a magnesium oxychloride cement (MOC) components to solidify harmful substances in textile sludge and studies the influence of textile sludge ash (TSA) on the mechanical properties and microstructure of MOC samples. The results indicated that adding 5 %-20 % TSA is beneficial for increasing the compressive strength of air-cured MOC paste and improving its water resistance. Meanwhile, the MOC sample shows volume expansion in 168 h, which is related to the further hydration of residual MgO. Incorporating 10 %-20 % TSA substantially increased the volume expansion ratio of the mixture compared to plain MOC sample. In addition, the porosity of TSA-modified MOC after water curing did not change significantly compared to the sample before water curing, while the pore structure of plain MOC after water curing significantly coarsened. This is mainly because TSA reacts with MOC and generates Mg-Al-Cl-Si-H and Mg-Cl-Si-H gels, consequently improving the water stability of MOC sample. At the nanoscale, the 3/5-phase crystal and unreacted MgO content in the 15 % TSA-modified MOC sample is relatively reduced by 7.79 % and 25 %, respectively, compared to the plain sample, but the 13 % gel phase is detected. In addition, the MOC component can effectively solidify heavy metal elements in textile sludge. For the leachate of 20 % TSA-modified MOC paste, the Ni element is not detected, and its solidifying effect on heavy elements such as Zn and Mn exceeded 99 %.

Product innovation design process combined Kano and TRIZ with AD: Case study.

In the era of rapid product iteration, companies need simple and effective methods to guide the entire process of product innovation design and enhance their product innovation capabilities. Most research focused on improving one or several steps in the product design process. Although some scholars have proposed methods that guided the entire process, they combined more than three different theories, which increased the difficulty of theoretical learning and the complexity of practical implementation. This paper proposed a product innovation design process composed of three theoretical methods: Kano, Axiomatic Design (AD), and Theory of the Solution of Inventive Problems (TRIZ). This new process guided the entire product design process with fewer theoretical methods, reducing the difficulty of learning and implementation. The paper demonstrated the effectiveness of this method through the design practice of a portable two-wheeled self-balancing vehicle. Additionally, the discussion section explored the method's potential from the design management perspective.

A therapeutic strategy of parthenolide in improving imiquimod-induced psoriasis-like skin inflammation targeting IL-36/NETs through skin transdermal therapeutic system.

BACKGROUND: Psoriasis is an inflammatory skin disease that occurs repeatedly over time. The natural product of sesquiterpene lactones, Parthenolide (Par), is isolated from Tanacetum parthenium L. (feverfew) which has significant effects on anti-inflammatory. The therapeutic effect of the medication itself is crucial, but different routes of administration of the same drug can also produce different effects. PURPOSE: The aim of our research sought to investigate the ameliorating effects of Par in psoriasis-like skin inflammation and its related mechanism of action. RESULTS: In the IMQ-induced model, intragastric administration of Par reduced the Psoriasis Area and Severity Index (PASI) score, improved skin erythema, scaling, and other symptoms. And Par decreased the expression of Ki67, keratin14, keratin16 and keratin17, and increased the expression of keratin1. Par could reduce IL-36 protein expressions, meanwhile the expression of Il1b, Cxcl1 and Cxcl2 mRNA were also decreased. Par regulated the expression levels of F4/80, MPO and NE. However, skin transdermal administration of Par was more effective. Similarly, Par attenuated IL-36γ, IL-1ß and caspase-1 activated by Poly(I:C) in in vitro and ex vivo. In addition, Par also reduced NE, PR3, and Cathepsin G levels in explant skin tissues. CONCLUSION: Par ameliorated psoriasis-like skin inflammation in both in vivo and in vitro, especially after treatment with transdermal drug delivery, possibly by inhibiting neutrophil extracellular traps and thus by interfering IL-36 signaling pathway. It indicated that Par provides a new research strategy for the treatment of psoriasis-like skin inflammation and is expected to be a promising drug.

Sternal sparing aortic valve replacement via right anterior minithoracotomy: An early experience.

Purpose: This study aims to evaluate the perioperative outcomes of aortic valve replacement (AVR) via right anterior minithoracotomy (RAT) during the learning curve. Methods: It was a retrospective, observational, cohort study of patients who underwent RAT AVR from June 2015 to April 2022. Primary outcomes measured were 30-day morbidity and mortality. Results: A total of 107 consecutive patients underwent elective RAT AVR. Our patients were mostly male (78.5%), elderly (mean 68.7 years), and obese (34.6%). A majority of the patients (93.5%) were of low operative risk. Median cross-clamp and bypass times were 95 and 123 minutes respectively. There was a statistically significant correlation between increase in number of cases and decrease in operative time. All patients had no paravalvular leak at discharge. There were no operative cardiovascular mortality or major morbidity including stroke, myocardial infarction, renal failure requiring dialysis, or vascular complication. No patient required intraoperative conversion to full sternotomy for completion of AVR. Conclusion: Our study demonstrated that RAT AVR can be safely introduced. The learning curve required in performing RAT AVR can be safely negotiated through training, previous experience in minimally invasive surgery, careful patient selection including use of preoperative computed tomography of the aorta, and introduction of sutureless/rapid deployment valves.

Network pharmacology-based investigation and experimental validation of the therapeutic potential and molecular mechanism of Danshen Chuanxiongqin injection in acute pancreatitis.

BACKGROUND: Danshen Chuanxiong Injection (DCI) has demonstrated significant clinical efficacy in the treatment of acute pancreatitis (AP); however, the precise molecular mechanisms underlying its therapeutic effects remain incompletely understood. OBJECTIVE: In this study, we employed network pharmacology analysis to comprehensively investigate the active components, potential targets, and signaling pathways involved in DCI-mediated treatment of AP. METHODS: We utilized the mouse pancreatic acinar cell line 266-6 to establish an cholecystokinin (CCK)-induced AP cell injury model and evaluated cell viability using the Cell counting kit-8 assay. Western blotting and quantitative PCR were employed to determine the expression levels of key target proteins and genes. RESULTS: Network pharmacology analysis identified a total of 144 active components and 430 potential targets within DCI. By integrating data from public databases, we identified 762 AP-related genes. Among these, we identified 93 potential targets that may be involved in the therapeutic effects of DCI for AP. These targets were significantly enriched in biological processes such as oxidative stress, regulation of cytokine production, leukocyte migration, and the TNF signaling pathway. Molecular docking studies revealed a high binding affinity between the active components and the key targets AKT1 and NFKBA, indicative of potential interaction. Additionally, CCK-induced acinar cell injury led to upregulation of AKT1, NFKBA, and P53 proteins, as well as TNF, IL6, and MMP9 genes. Conversely, treatment with DCI dose-dependently attenuated CCK-induced acinar cell injury and restored the expression levels of the aforementioned proteins and genes. CONCLUSION: Overall, this study provides a comprehensive understanding of the molecular mechanisms underlying the therapeutic effects of DCI in the treatment of AP. Our findings confirm the protective effect of DCI against CCK-induced acinar cell injury and its regulation of key targets.

Catheter ablation of atrial fibrillation in patients with left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.

Heating tumors with tumor cell-derived nanoparticles to enhance chemoimmunotherapy for colorectal cancer.

Aim: To investigate the mechanism of doxorubicin (DOX)-induced immunogenic cell death (ICD) and to improve immunotherapy efficacy. Materials & methods: In this study, hybrid vesicles containing DOX (HV-DOX) were prepared by thin-film hydration with extrusion, and the formulated nanoparticles were characterized physically. Furthermore, in vitro experiments and animal models were used to investigate the efficacy and new mechanisms of chemotherapy combined with immunotherapy. Results: DOX improved tumor immunogenicity by alkalinizing lysosomes, inhibiting tumor cell autophagy and inducing ICD. HVs could activate dendritic cell maturation, synergistically enhancing chemotherapeutic immunity. Conclusion: The mechanism of DOX-induced ICD was explored, and antitumor immunity was synergistically activated by HV-DOX to improve chemotherapeutic drug loading and provide relevant antigenic information.

Blocking brown adipocyte ß3-adrenoceptor attenuates blood-spinal cord barrier impairment and chronic postsurgical pain in a rat model of preoperative stress.

Preoperative stress has been recognized as an independent risk factor for chronic postsurgical pain (CPSP). However, the underlying mechanisms of CPSP influenced by preoperative stress remain elusive. Previous studies indicated that excessive stress could induce disruption of the blood-spinal cord barrier (BSCB). We wondered whether and how BSCB involves in CPSP by using a single prolonged stress (SPS) combining plantar incision model in male rats to mimic preoperative stress-related postsurgical pain. Here, we observed that preoperative SPS-exposed rats exhibited relentless incisional pain, which was accompanied by impairment of BSCB and persistent elevation of serum IL-6. Intraperitoneal injections of Tocilizumab (an IL-6 receptor monoclonal antibody) not only mitigated BSCB breakdown but also alleviated pain behaviors. In addition, intervening ß3-adrenoceptor (ADRB3) signaling in brown adipocytes by SR59230a (a specific ADRB3 antagonist) treatment or removal of brown adipose tissues could effectively decrease serum IL-6 levels, ameliorate BSCB disruption, and alleviate incisional pain. Further results displayed that SI-exposed rats also showed markedly spinal microglia activation. And exogenous His-tagged IL-6 could pass through the disrupted BSCB, which might contribute to microglia activation. Injection of SR59230a or ablation of brown adipose tissues could effectively reduce the activation of spinal microglia. Thus, our findings suggest that serum IL-6 induced by brown adipocyte ADRB3 signaling contributed to BSCB disruption and spinal microglia activation, which might be involved in preoperative stress mediated CPSP. This work indicates a promising treatment strategy for preoperative stress induced CPSP by blocking ADRB3.

Unraveling the molecular freezing behavior of water on a calcium silicate hydrate matrix.

The hydration process of cement-based materials primarily results in the formation of calcium silicate hydrate (CSH), which is crucial in deciding how long concrete will last. This study utilizes molecular dynamics simulation technology to explore the freezing behavior of pure water solutions within various calcium silicate hydrate (CSH) matrices. The investigated matrices encompass four different Ca/Si ratios. According to the simulation, as ice crystals develop close to the surface of CSH, the CSH matrix strengthens its hydrogen and ionic interactions with water molecules, which effectively prevents water molecules from crystallizing and nucleating. Consequently, these molecules compose an unfrozen water film structure that bridges between ice crystals and the CSH matrix. The research also reveals an intriguing relationship between silica chain behavior on the Ca/Si ratio and the CSH surface. Surface flaws arise as a result of the silica chains of CSH breaking into shorter segments as the Ca/Si ratio increases. These surface defects manifest as grooves on the matrix's surface, effectively capturing and retaining specific water molecules. The CSH matrix's hydrogen bonds with water molecules are weakened as a result of this process, facilitating their participation in the crystallization process, and leading to a thinner unfrozen water film thickness with an increased Ca/Si ratio. This study contributes to a greater knowledge of the performance and dependability of cement-based products by offering molecular-level insights into the freezing actions of liquids in gel pores.

Biochemical and Transcriptome Analysis Reveals Pigment Biosynthesis Influenced Chlorina Leaf Formation in Anoectochilus roxburghii (Wall.) Lindl.

Anoectochilus roxburghii (Wall.) Lindl is a perennial herb of the Orchidaceae family; a yellow-green mutant and a yellow mutant were obtained from the wild type, thereby providing good material for the study of leaf color variation. Pigment content analysis revealed that chlorophyll, carotenoids, and anthocyanin were lower in the yellow-green and yellow mutants than in the wild type. Transcriptome analysis of the yellow mutant and wild type revealed that 78,712 unigenes were obtained, and 599 differentially expressed genes (120 upregulated and 479 downregulated) were identified. Using the Kyoto Encyclopedia of Genes and Genomes pathway analysis, candidate genes involved in the anthocyanin biosynthetic pathway (five unigenes) and the chlorophyll metabolic pathway (two unigenes) were identified. Meanwhile, the low expression of the chlorophyll and anthocyanin biosynthetic genes resulted in the absence of chlorophylls and anthocyanins in the yellow mutant. This study provides a basis for similar research in other closely related species.

Furosemide Responsiveness Predicts Acute Kidney Injury Progression After Cardiac Surgery.

BACKGROUND: As patients with acute kidney injury (AKI) progress to a higher stage, the risk for poor outcomes dramatically rises. Early identification of patients at high risk for AKI progression remains a major challenge. This study aimed to evaluate the value of furosemide responsiveness (FR) for predicting AKI progression in patients with initial mild and moderate AKI after cardiac surgery. METHODS: We performed 2 separate exploratory analyses. The Zhongshan cohort was a single-center, prospective, observational cohort, whereas the Beth Israel Deaconess Medical Center cohort was a single-center, retrospective cohort. We calculated 2 FR parameters for each patient, namely the FR index and modified FR index, defined as 2-hour urine output divided by furosemide dose (FR index, mL/mg/2 h) and by furosemide dose and body weight (modified FR index, mL/[mg·kg]/2 h), respectively. The primary outcome was AKI progression within 7 days. RESULTS: AKI progression occurred in 80 (16.0%) and 359 (11.3%) patients in the Zhongshan and Beth Israel Deaconess Medical Center cohorts, respectively. All FR parameters (considered continuously or in quartiles) were inversely associated with risk of AKI progression in both cohorts (all adjusted P < .01). The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models involving C-index, net reclassification improvement, and integrated discrimination improvement index in both cohorts (all P < .01). CONCLUSIONS: FR parameters were inversely associated with risk of AKI progression in patients with mild and moderate AKI after cardiac surgery. The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models.

Effect of mesenchymal stromal cells transplantation on the outcomes of patients with knee osteoarthritis: A systematic review and meta-analysis.

Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell transplantation from different sources for the treatment of knee osteoarthritis (KOA) remains controversial. This study integrates and evaluates the previously published data of stem cell transplantation for KOA to explore the curative effect of different stem cells. We conducted a meta-analysis of randomized controlled trials on stem cell therapy for KOA. Measures of efficacy included Visual Analog Scale (VAS), Lequesne index, Lysholm Knee Scoring Scale (LKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Joint injury was evaluated through the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. We analyzed 16 studies involving 875 KOA patients. The stem cell treatment showed significant VAS reduction from the third month onwards. Subgroup analysis suggested the most significant pain relief at different postoperative months came from adipose-derived and umbilical cord-derived stem cells. Autologous adipose tissue resulted in better pain alleviation compared with allogenic. However, autologous bone marrow stem cells did not show increased pain relief over allogeneic ones. Combination therapy (HA and/or PRP) showed no effect. Autologous adipose-derived stem cells demonstrate the most effective recovery of knee joint function. In WORMS assessment, there was no significant difference between the stem cell group and control. Stem cell transplantation proved safe and effective for KOA treatment. Different sources stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.

Family Integrated Care Shortens the Duration of Home Oxygen Therapy in Infants With Bronchopulmonary Dysplasia.

BACKGROUND: There have been few reports on whether family integrated care (FIC) can help premature infants with moderate to severe bronchopulmonary dysplasia (BPD) to shorten the duration of home oxygen therapy (HOT). PURPOSE: To investigate the effect of FIC on the duration of HOT in premature infants with moderate to severe BPD. METHODS: The subjects were retrospectively selected from premature infants with moderate to severe BPD in our center between June 2019 and December 2021. Patients were divided into the FIC group (n = 47) and the non-FIC group (n = 34). For univariate analysis, t test, Mann-Whitney U test, Pearson χ 2 test, or Fisher exact test was performed to explore the differences between the 2 groups. For multivariate analysis, simple and multiple linear regression was conducted to explore the effect of FIC on the duration of HOT. RESULTS: (1) The duration of HOT and length of stay after grouping were significantly shorter in the FIC group than in the non-FIC group ( P < .05). (2) The results of linear regression further revealed that FIC could significantly shorten the duration of HOT (simple linear regression, FIC [A] B : -12.709, 95% confidence interval (CI): -21.665 to -3.753; multiple linear regression, FIC [B] B : -11.419, 95% CI: -18.055 to -4.783). IMPLICATIONS FOR PRACTICE AND RESEARCH: FIC improved the optimal target oxygen saturation ratio before discharge and shortened the duration of HOT in premature infants with moderate and severe BPD. FIC should be promoted in China's neonatal intensive care units, though it puts forward new requirements for nursing education and training.

Causal relationships between plasma lipids and sepsis: A Mendelian randomization study.

Although observational studies have indicated that plasma lipids are associated with an increased risk of sepsis, due to confounders and reverse causality, the causal relationship remains unclear. This study was designed to assess the causal effects of plasma lipid levels on sepsis. We used a 2-sample Mendelian randomization (MR) method to evaluate the causal effect of plasma lipids on sepsis. MR analysis employs methods such as inverse variance weighted, MR-Egger regression, weighted median regression (WME), simple mode and weighted mode. The inverse variance weighted (IVW) method was predominantly utilized to assess causality. Heterogeneity was affirmed by Cochran Q test, while pleiotropy was corroborated by MR-Egger regression analysis. The robustness and reliability of the results were demonstrated through "leave-one-out" sensitivity analysis. Instrumental variables included 226 single-nucleotide polymorphisms (SNPs), comprising of 7 for triglyceride (TG), 169 for high-density lipoprotein cholesterol (HDL-C), and 50 for low-density lipoprotein cholesterol (LDL-C). The risk of sepsis appeared to increase with rising LDL-C levels, as indicated by the inverse variance weighted analysis (OR 1.11, 95% CI from0.99 to1.24, P = 0.068). However, no causality existed between LDL-C, HDL-C, TG and sepsis. Two-sample MR analysis indicated that increased LDL-C level is a risk factor for sepsis, while TG and HDL-C levels have protective effects against sepsis. However, no significant causal relationship was found between TG, HDL-C, and LDL-C levels and sepsis.

Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.

PURPOSE: To explore the potential role of signal transducer and activator of transcription 5A (STAT5A) in the metastasis of breast cancer, and its mechanism of regulation underlying. METHODS AND RESULTS: TCGA datasets were used to evaluate the expression of STAT5A in normal and different cancerous tissues through TIMER2.0, indicating that STAT5A level was decreased in breast cancer tissues compared with normal ones. Gene Set Enrichment Analysis predicted that STAT5A was associated with the activation of immune cells and cell cycle process. We further demonstrated that the infiltration of immune cells was positively associated with STAT5A level. Influorescence staining revealed the expression and distribution of F-actin was regulated by STAT5A, while colony formation assay, wound healing and transwell assays predicted the inhibitory role of STAT5A in the colony formation, migratory and invasive abilities in breast cancer cells. In addition, overexpression of the Notch3 intracellular domain (N3ICD), the active form of Notch3, resulted in the increased expression of STAT5A. Conversely, silencing of Notch3 expression by siNotch3 decreased STAT5A expression, supporting that STAT5A expression is positively associated with Notch3 in human breast cancer cell lines and breast cancer tissues. Mechanistically, chromatin immunoprecipitation showed that Notch3 was directly bound to the STAT5A promoter and induced the expression of STAT5A. Moreover, overexpressing STAT5A partially reversed the enhanced mobility of breast cancer cells following Notch3 silencing. Low expression of Notch3 and STAT5A predicted poorer prognosis of patients with breast cancer. CONCLUSION: The present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.

LncRNA PVT1 induces apoptosis and inflammatory response of bronchial epithelial cells by regulating miR-30b-5p/BCL2L11 axis in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a serious health burden worldwide with high mortality. LncRNA plasmacytoma variant translocation 1 (PVT1) has been illustrated to serve as a biomarker for COPD progression. Nonetheless, its specific functions and mechanisms in COPD are unclarified. METHODS: Cigarette smoke extract (CSE) was utilized to stimulate 16HBE cells, and cigarette smoke combining with lipopolysaccharide (LPS) was employed to induce COPD in rats. Western blotting and RT-qPCR were utilized for measuring protein and RNA levels. Flow cytometry was implemented for detecting cell apoptosis. Concentrations of inflammatory factors TNF-α and IFN-γ were examined using ELISA. Luciferase reporter assay was utilized for verifying the interaction between molecules. Hematoxylin-eosin staining was performed for histological analysis of rat lung tissues. RESULTS: PVT1 was highly expressed in CSE-stimulated 16HBE cells and the lungs of COPD rats. PVT1 depletion restored the viability, restrained apoptosis and hindered inflammatory cytokine production in 16HBE cells under CSE treatment and alleviated pathological damages in COPD rats. PVT1 bound to miR-30b-5p and miR-30b-5p targeted BCL2 like 11 (BCL2L11). Overexpressing BCL2L11 offset the above effects mediated by PVT1 in CSE-triggered 16HBE cells. CONCLUSION: PVT1 enhances apoptosis and inflammation of 16HBE cells under CSE stimulation by modulating miR-30b-5p/BCL2L11 axis.