Evaluating the impact of Sacubitril/valsartan on diastolic function in patients with heart failure: A systematic review and meta-analysis.

BACKGROUND: Heart failure is a common and severe condition, often complicated by diastolic dysfunction. Current standard therapies such as ACEIs and ARBs have limited efficacy in managing diastolic function. Sacubitril/Valsartan, an emerging therapy, warrants rigorous investigation to elucidate its impact on diastolic function in heart failure patients. METHODS: This systematic review and meta-analysis were conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and utilized the PICO schema. Searches were performed on 4 databases-PubMed, Embase, Web of Science, and Cochrane Library-without temporal restrictions. Inclusion and exclusion criteria were strictly defined, and quality assessments were conducted using the Cochrane Collaboration Risk of Bias tool. Both fixed-effects and random-effects models were used for statistical analysis, depending on inter-study heterogeneity assessed by I2 statistics and Chi-square tests. RESULTS: Out of 1129 identified publications, 8 studies met the criteria and were included in the meta-analysis. These studies consisted of both randomized controlled trials and cohort studies and featured diverse global populations. Significant reductions were found in the echocardiographic parameter E/e' ratio and LAVi upon treatment with Sacubitril/Valsartan compared to standard therapies, with mean differences of -1.38 and -4.62, respectively, both with P values < .01. CONCLUSIONS: This meta-analysis demonstrates that Sacubitril/Valsartan significantly improves diastolic function parameters in heart failure patients compared to standard treatments. These findings underscore the potential benefits of Sacubitril/Valsartan in the management of heart failure, particularly for patients with diastolic dysfunction.

FERREG: ferroptosis-based regulation of disease occurrence, progression and therapeutic response.

Ferroptosis is a non-apoptotic, iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species. In recent years, a large and growing body of literature has investigated ferroptosis. Since ferroptosis is associated with various physiological activities and regulated by a variety of cellular metabolism and mitochondrial activity, ferroptosis has been closely related to the occurrence and development of many diseases, including cancer, aging, neurodegenerative diseases, ischemia-reperfusion injury and other pathological cell death. The regulation of ferroptosis mainly focuses on three pathways: system Xc-/GPX4 axis, lipid peroxidation and iron metabolism. The genes involved in these processes were divided into driver, suppressor and marker. Importantly, small molecules or drugs that mediate the expression of these genes are often good treatments in the clinic. Herein, a newly developed database, named 'FERREG', is documented to (i) providing the data of ferroptosis-related regulation of diseases occurrence, progression and drug response; (ii) explicitly describing the molecular mechanisms underlying each regulation; and (iii) fully referencing the collected data by cross-linking them to available databases. Collectively, FERREG contains 51 targets, 718 regulators, 445 ferroptosis-related drugs and 158 ferroptosis-related disease responses. FERREG can be accessed at https://idrblab.org/ferreg/.

Preparation and properties of polyvinyl alcohol/chitosan-based hydrogel with dual pH/NH3 sensor for naked-eye monitoring of seafood freshness.

To address the issue of food spoilage causing health and economic loss, we developed a pH/NH3 dual sensitive hydrogel based on polyvinyl alcohol/chitosan (PVA/CS) containing chitosan-phenol red (CP). The CP was synthesized via Mannich reaction and immobilized it in PVA/CS hydrogel through freezing/thawing method to prepare the final PVA/CS/CP hydrogel. The synthesis of CP was confirmed by 1H NMR, FT-IR, XRD, UV-vis, and XPS. The characteristics of hydrogel were evaluated by FT-IR, XRD, SEM, mechanical properties, thermal stability, leaching, and color stability tests. The PVA/CS/CP hydrogel showed distinctly different color at various pH and NH3 vapor levels (yellow to purple). The hydrogel exhibited obvious color changes (ΔE = 46.95) in response to shrimp spoilage, stored at 4 °C. It showed positive and strong correlation between the ΔE values of the indicator hydrogel and total volatile basic nitrogen (TVB-N) as (R2 = 0.9573) and with pH as (R2 = 0.8686), respectively. These results clearly show that the PVA/CS/CP hydrogel could be applied for naked-eye real-time monitoring of seafood freshness in intelligent packaging.

A Novel Multifunctional Crosslinking PVA/CMCS Hydrogel Containing Cyclic Peptide Actinomycin X2 and PA@Fe with Excellent Antibacterial and Commendable Mechanical Properties.

Bacterial infected environments and resulting bacterial infections have been threatening the human health globally. Due to increased bacterial resistance caused by improper and excessive use of antibiotics, antibacterial biomaterials are being developed as alternatives to antibiotics in some cases. Herein, an advanced multifunctional hydrogel with excellent antibacterial properties, enhanced mechanical properties, biocompatibility and self-healing performance, was designed through freezing-thawing method. This hydrogel network is composed of polyvinyl alcohol (PVA), carboxymethyl chitosan (CMCS), protocatechualdehyde (PA), ferric iron (Fe) and an antimicrobial cyclic peptide actinomycin X2 (Ac.X2). The double dynamic bonds among protocatechualdehyde (PA), ferric iron (Fe) and carboxymethyl chitosan containing coordinate bond (catechol-Fe) as well as dynamic Schiff base bonds and hydrogen bonds endowed the hydrogel with enhanced mechanical properties. Successful formation of hydrogel was confirmed through ATR-IR and XRD, and structural evaluation through SEM analysis, whereas mechanical properties were tested with electromechanical universal testing machine. The resulting PVA/CMCS/Ac.X2/PA@Fe (PCXPA) hydrogel has favorable biocompatibility and excellent broad-spectrum antimicrobial activity against both S. aureus (95.3 %) and E. coli (90.2 %) compared with free-soluble Ac.X2, which exhibited subpar performance against E. coli reported in our previous studies. This work provides a new insight on preparing multifunctional hydrogels containing antimicrobial peptides as antibacterial material.

Preparation and Characterization of a Silk Fibroin/Polyurethane Fiber Blend Membrane Containing Actinomycin X2 with Excellent Mechanical Properties and Enhanced Antibacterial Activities.

Development of suitable antimicrobial biomaterials for hygienic wound dressing and healing is an important requirement for medical application. Durable mechanical properties increase the application range of biomaterial in different environmental and biological conditions. Due to the inherent brittleness of silk fibroin (SF), polyurethane fiber (PUF) was used to modify SF containing actinomycin X2 (Ac.X2) to prepare silk fibroin@actinomycin X2 /polyurethane fiber (ASF/PUF) blend membranes. The ASF/PUF blend membrane was developed by solution casting method. Incorporation of PUF improved the flexibility of material and introduction of Ac.X2 has increased antibacterial activity of materials. Excellent mechanical properties (tensile strength up to 25.7 MPa and elongation at break up to 946.5 %) of 50 % SF+50 % PUF blend membrane were proved by tensile testing machine. FT-IR spectra, TGA, contact angle and DMA were tested to prove the blend membrane's physico-chemical characteristics. ASF/PUF blend membrane displayed satisfactory antibacterial activity against S. aureus, and the cytotoxicity tests showed that the blend membrane has better biosafety compared to directly applied Ac.X2 in soluble form. These results suggest that the modification of SF through PUF for development of flexible antibacterial membranes has great potential application value in the field of silk-like material fabrication.

Dynamic volume variation of uterine leiomyomas during pregnancy.

OBJECTIVE: To investigate the volume variation of uterine leiomyomas and explore factors predicting their growth trends during pregnancy. METHOD: A retrospective observational study was performed on pregnant women with uterine leiomyomas between January 2016 and April 2020. The uterine leiomyoma volume was acquired from obstetrical ultrasound at the first, second, and third trimesters of gestation. A binary logistic regression analysis was conducted to explore the factors influencing the volume variation of uterine leiomyomas during pregnancy. RESULTS: A total of 278 pregnant women diagnosed with uterine leiomyomas were enrolled. The volumetric increase in uterine leiomyomas during pregnancy exhibited a higher growth rate from the first to second trimester (34.09%) than that from the second to third trimester (30.08%). Smaller uterine leiomyomas were more likely to increase in size from the first to second trimester and from the first to third trimester. Retroplacental uterine leiomyomas were more likely to increase in volume than that for uterine leiomyomas located away from the placenta in pregnant women from the second to third trimester. CONCLUSION: The uterine leiomyoma volume was potentially enlarged in a nonlinear growth pattern during pregnancy, which was associated with the former volume of uterine leiomyomas and the spatial relationship between leiomyoma-placental site.

Measurement of pre-treatment inflammatory cytokine levels is valuable for prediction of treatment efficacy to tumor necrosis factor inhibitor in axial spondyloarthritis patients.

AIM: To evaluate the correlation of inflammatory cytokines with the treatment response to tumor necrosis factor inhibitor (TNFi) in axial spondyloarthritis (axSpA) patients. METHODS: This study enrolled 86 axSpA patients and 20 healthy controls (HCs). Inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-12, IL-17A, IL-21, IL-23, and IL-32 were determined in serum samples of axSpA patients before treatment and in HCs after enrollment. All patients received 40 mg adalimumab every 2 weeks for 12 weeks; meanwhile, ASAS40 (40 criteria of the Assessment by the SpondyloArthritis International Society) response rates were evaluated at weeks 2, 4, 8, and 12. RESULTS: Most inflammatory cytokines were elevated in axSpA patients compared with HCs (all P < 0.05) except for IL-32 (P = 0.101). In axSpA patients, ASAS40 response rates were 0%, 19.5%, 34.5%, 47.1%, and 56.3% at weeks 0, 2, 4, 8, and 12, respectively. Baseline [interquartile range] IL-6 (47.3 [32.5-53.4] pg/mL vs 31.7 [23.0-50.9] pg/mL, P = 0.005) and IL-17A (127.9 [90.7-149.5] pg/mL vs 96.6 [56.1-112.6] pg/mL, P < 0.001) were higher in axSpA patients with ASAS40 response compared with those without ASAS40 response, while baseline TNF-α, IL-1ß, IL-12, IL-21, IL-23, and IL-32 were not different between them (all P > 0.050). Multivariate logistic regression analysis disclosed that baseline IL-17A (P = 0.037), C-reactive protein (P = 0.012), and history of TNF inhibitor (P = 0.029) were independently associated with ASAS40 response. Furthermore, baseline IL-17A, C-reactive protein, history of TNFi, and their combination had an acceptable to good ability for predicting ASAS40 response. CONCLUSION: Measurement of pre-treatment inflammatory cytokine levels is valuable for predicting treatment efficacy of TNFi in axSpA patients.

MAT2A facilitates PDCD6 methylation and promotes cell growth under glucose deprivation in cervical cancer.

The underlying mechanisms of methionine adenosyltransferase 2 A (MAT2A)-mediated cervical cancer progression under nutrient stress are largely elusive. Therefore, our study aims to investigate molecular mechanism by which MAT2A-indcued cervical oncogenesis. The interaction between MAT2A and programmed cell death protein 6 (PDCD6) in cervical cancer cell lines was detected by immunoprecipitation, immunoblotting and mass spectrometric analysis. A panel of inhibitors that are linked to stress responsive kinases were utilized to detect related pathways by immunoblotting. Cell proliferation and apoptosis were investigated by CCK-8 and flow cytometry. Apoptosis related protein level of Bcl-2, Bax and Caspase-3 was also analyzed in cells with PDCD6 K90 methylation mutation. The association between MAT2A and PDCD6 was detected by immunohistochemistry and clinicopathological characteristics were further analyzed. We found that the interaction between MAT2A and PDCD6 is mediated by AMPK activation and facilitates PDCD6 K90 methylation and further promotes protein stability of PDCD6. Physiologically, expression of PDCD6 K90R leads to increased apoptosis and thus suppresses growth of cervical cancer cells under glucose deprivation. Furthermore, the clinical analysis indicates that the MAT2A protein level is positively associated with the PDCD6 level, and the high level of PDCD6 significantly correlates with poor prognosis and advanced stages of cervical cancer patients. We conclude that MAT2A facilitates PDCD6 methylation to promote cervical cancer growth under glucose deprivation, suggesting the regulatory role of MAT2A in cellular response to nutrient stress and cervical cancer progression.

Influence of biochar remediation on Eisenia fetida in Pb-contaminated soils.

In this study, the remediation influence of maize straw biochar on earthworms (Eisenia fetida) in contaminated soils (with Pb at 0, 300, 700, and 1000 mg kg-1) amended with different amounts of biochar (0%, 1%, 3%, and 5%) was investigated. The results showed that applying biochar to metal-polluted soils effectively reduced the mobility of Pb, promoting the transformation of Pb from exchangeable (EXC) and bound-to-carbonate (Carb) fractions to Fe/Mn oxide (FeMnOx), organic bound (ORG) and residual (RES) fractions. Consequently, a reduction in the mortality and weight loss of earthworms was also achieved by biochar. The accumulation amount of Pb in earthworms steadily increased with exposure time, and with the increasing dosage of biochar, the accumulated Pb decreased by 50.8-78.0% (300 mg kg-1), 30.9-67.3% (700 mg kg-1), and 17.4-55.1% (1000 mg kg-1), which was significantly positively correlated with the mortality of earthworms. Simultaneously, the application of biochar increased the soil pH (0.05-0.23 units), cation exchange capacity (CEC) (0.26-4.54 cmol kg-1), and content of organic matter (0.54-11.66%). There were higher soil enzyme activities (including sucrase activity, urease activity, and alkaline phosphatase activity) in the treatments with a biochar addition of 3%. Through remediation, Proteobacteria (50.82%), Actinobacteriota (32.37%), Firmicutes (4.83%) and Bacteroidota (1.88%) were the most important phyla in the microbiota communities. Furthermore, soil pH value and leaching toxicity concentration showed the most striking effects on earthworms. Therefore, the influence of earthworms must be taken into account in the remediation of Pb-contaminated soil with biochar.

The role of circular RNA plasmacytoma variant translocation 1 as a biomarker for prognostication of acute myeloid leukemia.

OBJECTIVE: Circular RNA plasmacytoma variant translocation 1 (circ-PVT1) has been reported to be an oncogene and serves as a prognostic biomarker in several solid cancers and hematological malignancies. However, no study has been performed on the tumorigenesis role of circ-PVT1 in acute myeloid leukemia (AML). Thus, this study aimed to evaluate the correlation of circ-PVT1 with disease risk, clinical characteristics, cytogenetics/molecular genetics, and prognosis of AML. METHODS: A total of 68 de novo AML patients, 30 disease controls and 30 health donors were enrolled in this study. Circ-PVT1 expression in bone marrow (BM) was determined. Complete remission (CR) status after induction therapy, event-free survival (EFS) and overall survival (OS) were evaluated in AML patients. RESULTS: Circ-PVT1 expression was different among AML patients, disease controls and health donors, which was highest in AML patients, followed by disease controls and lowest in health donors. Meanwhile, circ-PVT1 could distinguish AML patients from health donors and disease controls by receiver operating characteristic curve analysis. Furthermore, circ-PVT1 was correlated with BM blasts and FLT3-ITD mutation, but not other clinical features, such as French-American-Britain subtypes in AML patients. Moreover, circ-PVT1 expression was lower in AML patients with CR compared with those without CR. Besides, high circ-PVT1 expression was correlated with shorter EFS and OS in AML patients. After adjustment by multivariate Cox's regression analysis, higher circ-PVT1 expression was an independent factor in predicting shorter EFS and OS for AML patients. CONCLUSION: Circ-PVT1 potentially serves as a biomarker for evaluating the prognosis of AML patients.

Elevated expression of Tweety homologue 3 predicts poor clinical outcomes in ovarian cancer.

Objective: To define the alteration of tweety homolog (TTYH) expression in patients with ovarian carcinoma (OC) and its correlation to prognosis. Methods: Kaplan-Meier (KM) plotter was used to evaluate the association between TTYHs expression and clinical outcomes of OC patients. The distribution of 20-year overall survival (OS) and progression-free survival (PFS) was estimated using KM survival plots. The mRNA expression of TTYHs in OC and normal ovarian tissues was confirmed by the Oncomine database. Then, using immunohistochemistry assay, the expression of TTYH1 and TTYH3 proteins in serous OC and normal ovarian tissues was detected. In addition, the protein and mRNA levels of TTYH1 and TTYH3 in human OC cell lines ES-2, A2780 and SKOV3 and normal ovarian epithelial cell lines IOSE80 were assessed by western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: TTYH1 possessed meaningful significance in predicting better prognosis in the serous, advanced stage, and well-differentiated OC patients, while TTYH3 expression predicted worse prognosis in serous, late-stage, and poorly differentiated OC patients. High expression of TTYH1 displayed an association with favorable PFS in OC patients with TP53 mutation. However, enhanced TTYH3 was related to an adverse clinical outcome in TP53-mutated OC patients. In addition, TTYH1 was related to a better clinical outcome in OC patients with platinums-based chemotherapy, but only indicated improved overall survival in OC patients who received taxol or platin + taxol chemotherapy. The up-regulated expression of TTYH3 predicted worse survival in OC patients receiving platin, taxol, or platin + taxol chemotherapy regimen. The levels of TTYH3 mRNA and protein were higher in OC cells and tissues when compared to normal ovarian cells and tissues. Conclusions: TTYH3 was a potential predictor for poor clinical outcome in OC patients, particularly in patients with serous, late-stage, poorly differentiated, TP53-mutation or the patients treated with chemotherapy regimens (platin, taxol, or platin + taxol).

Multiple imputation of maritime search and rescue data at multiple missing patterns.

Based on the missing situation and actual needs of maritime search and rescue data, multiple imputation methods were used to construct complete data sets under different missing patterns. Probability density curves and overimputation diagnostics were used to explore the effects of multiple imputation. The results showed that the Data Augmentation (DA) algorithm had the characteristics of high operation efficiency and good imputation effect, but the algorithm was not suitable for data imputation when there was a high data missing rate. The EMB algorithm effectively restored the distribution of datasets with different data missing rates, and was less affected by the missing position; the EMB algorithm could obtain a good imputation effect even when there was a high data missing rate. Overimputation diagnostics could not only reflect the data imputation effect, but also show the correlation between different datasets, which was of great importance for deep data mining and imputation effect improvement. The Expectation-Maximization with Bootstrap (EMB) algorithm had a poor estimation effect on extreme data and failed to reflect the dataset's variability characteristics.

Exosomal microRNA­146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2­mediated PI3K/Akt axis.

The carrier role of exosomes from human umbilical cord mesenchymal stem cells (hUCMSCs) containing microRNAs (miRNAs) has been implicated in gene and drug therapy. The aim of the present study was to investigate the role of exosomal microRNA­146a (miR­146a) from hUCMSCs in ovarian cancer (OC). Following the generation of docetaxel (DTX)­resistant SKOV3 cells and taxane­resistant A2780 cells, exosomes were isolated from hUCMSCs and added to the chemoresistant cells. Microarray analysis revealed that miR­146a expression was upregulated in DTX/SKOV3 cells among 15 ectopically expressed miRNAs. Analysis using the StarBase and miRSearch databases demonstrated that miR­146a targeted laminin γ2 (LAMC2), which was further verified using dual­luciferase reporter assays. Subsequently, miR­146a inhibitor or LAMC2 overexpression vectors were transfected into hUCMSCs or OC cells, respectively, and their effects on growth and chemoresistance in OC cells were assessed. The hUCMSC­derived exosomes reduced cell growth and chemoresistance in OC. Furthermore, hUCMSC­derived exosomes with miR­146a expression knocked down increased OC cell growth and chemoresistance, which was mediated by the PI3K/Akt signaling pathway via LAMC2.

Production of a new tetracyclic triterpene sulfate metabolite sambacide by solid-state cultivated Fusarium sambucinum B10.2 using potato as substrate.

The aim of this work is to explore integracide analogues from secondary metabolites of microorganisms. A new tetracyclic triterpene sulfate was produced by solid-state fermentation (SSF) with Fusarium sambucinum B10.2. The tetracyclic triterpene sulfate was identified as (3S,5R,10S,11S,12S,13R,17R,20R)-4,4-dimethylergosta-8,14,24-triene-3,11,12-triol-12-acetate, 3-sulfate on the basis of HRESIMS, NMR and electronic circular dichroism (ECD) spectra and named sambacide (1). The antibacterial and antifungal assays of sambacide (1) showed significant antibacterial activities against Staphylococcus aureus and Escherichia coli. The fermentation conditions including culture media, fermentation temperature and time, were optimized. And potato was selected as the fermentation substrate, 28°C was used as the fermentation temperature, and 20-days fermentation time was determined for F. sambucinum-SSF to produce sambacide (1) with a high yield of 19.04±0.82g/kg. This paper provides an efficient approach to produce the antibacterial and antifungal agent sambacide (1) in a very high yield.

Interactions in different domains of truxenone supramolecular assembly on Au(111).

The two-dimensional assemblies of truxenone, diindeno[1,2-a;1',2'-c]fluorene-5,10,15-trione, on the Au(111) surface have been studied by scanning tunnelling microscopy in ultrahigh vacuum. It is found that the truxenone monolayer on Au(111) exhibits different two-dimensional supramolecular structures. The investigation using scanning tunnelling microscopy combined with the density functional theory calculations can be a helpful approach to understand the complicated supramolecular structures of truxenone self-assembly on Au(111).