Enhancing Oxygen Activation Ability by Composite Interface Construction over a 2D Co3O4-Based Monolithic Catalyst for Toluene Oxidation.

Developing robust metal-based monolithic catalysts with efficient oxygen activation capacity is crucial for thermal catalytic treatment of volatile organic compound (VOC) pollution. Two-dimensional (2D) metal oxides are alternative thermal catalysts, but their traditional loading strategies on carriers still face challenges in practical applications. Herein, we propose a novel in situ molten salt-loading strategy that synchronously enables the construction of 2D Co3O4 and its growth on Fe foam for the first time to yield a unique monolithic catalyst named Co3O4/Fe-S. Compared to the Co3O4 nanocube-loaded Fe foam, Co3O4/Fe-S exhibits a significantly improved catalytic performance with a temperature reduction of 44 °C at 90% toluene conversion. Aberration-corrected scanning transmission electron microscopy and theoretical calculation suggest that Co3O4/Fe-S possesses abundant 2D Co3O4/Fe3O4 composite interfaces, which promote the construction of active sites (oxygen vacancy and Co3+) to boost oxygen activation and toluene chemisorption, thereby accelerating the transformation of reaction intermediates through Langmuir-Hinshelwood (L-H) and Mars-van Krevelen (MvK) mechanisms. Moreover, the growth mechanism reveals that 2D Co3O4/Fe3O4 composite interfaces are generated in situ in molten salt, inducing the growth of 2D Co3O4 onto the surface lattice of 2D Fe3O4. This study provides new insights into enhancing oxygen activation and opens an unprecedented avenue in preparing efficient monolithic catalysts for VOC oxidation.

Preovulation body mass index and pregnancy after first frozen embryo transfer in patients with polycystic ovary syndrome and insulin resistance.

OBJECTIVE: To examine the association between preovulation body mass index and pregnancy outcomes after frozen embryo transfer in patients with polycystic ovary syndrome with insulin resistance. DESIGN: This was a single-center, retrospective cohort study. SUBJECTS: Women with infertility, diagnosed with polycystic ovary syndrome and insulin resistance, and treated at the Reproductive Medicine Center, Second People's Hospital of Nanning, China, between January 2020 and August 2023, were included. EXPOSURE: Patients were divided into four groups according to their body mass index (BMI): slim (<18.5 kg/m2), normal (18.5≤ BMI <24 kg/m2), overweight (24≤ BMI <28 kg/m2), or obese (≥28 kg/m2). MAIN OUTCOME MEASURES: The main pregnancy outcomes included rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy. RESULTS: In total, 282 eligible patients were included. A linear association was observed between the BMI and clinical pregnancy outcomes of the first frozen embryo transfer (P for nonlinearity>0.05). After accounting for all potential variables, each 1 kg/m2 increase in BMI was linked to a 2% decrease in the embryo implantation rate (P<0.05), 11% decrease in the frequency of biochemical pregnancy (P<0.05), and 9% decrease in the both clinical (P<0.05) and ongoing pregnancy rates. CONCLUSION: In patients with polycystic ovary syndrome and insulin resistance, a higher BMI was associated with lower rates of embryo implantation, biochemical pregnancy, clinical pregnancy, and ongoing pregnancy.

Nanoparticles (NPs)-mediated lncMALAT1 silencing to reverse cisplatin resistance for effective hepatocellular carcinoma therapy.

Platinum-based chemotherapy has been widely used for clinical cancer treatment, but drug resistance is the main barrier to induce the poor prognosis of cancer patients. Long non-coding RNAs (lncRNAs) have been recognized as a type of new cancer therapeutic targets due to their important role in regulating cancer progression such as drug resistance. However, it is still challenged to effectively intervene the expression of lncRNAs as they are usually located at various subcellular organelles (e.g., nucleus, mitochondrion, and endoplasmic reticulum). We herein developed an endosomal pH-responsive nanoparticle (NP) platform for small interfering RNA (siRNA) and cisplatin prodrug co-delivery and effective cisplatin-resistant hepatocellular carcinoma (HCC) therapy. This co-delivery nanoplatform is comprised of a hydrophilic polyethylene glycol (PEG) shell and a hydrophobic poly (2-(diisopropylamino)ethyl methacrylate) (PDPA) core, in which cisplatin prodrug and electrostatic complexes of nucleus-targeting amphiphilic peptide (NTPA) and siRNA are encapsulated. After intravenous injection and then uptake by tumor cells, the endosomal pH could trigger the dissociation of nanoplatform and enhance the endosomal escape of loaded cisplatin prodrug and NTPA/siRNA complexes via the "proton sponge" effect. Subsequently, the NTPA/siRNA complexes could specifically transport siRNA into the nucleus and efficiently reverse cisplatin resistance via silencing the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncMALAT1) mainly localized in the nucleus, ultimately inhibiting the growth of cisplatin-resistant HCC tumor.

Nonlinear dynamic transfer partial least squares for domain adaptive regression.

Aiming to address soft sensing model degradation under changing working conditions, and to accommodate dynamic, nonlinear, and multimodal data characteristics, this paper proposes a nonlinear dynamic transfer soft sensor algorithm. The approach leverages time-delay data augmentation to capture dynamics and projects the augmented data into a latent space for constructing a nonlinear regression model. Two regular terms, distribution alignment regularity and first-order difference regularity, are introduced during data projection to address data distribution disparities. Laplace regularity is incorporated into the nonlinear regression model to ensure geometric structure preservation. The final optimization objective is formulated within the framework of partial least squares, and hyperparameters are determined using Bayesian optimization. The effectiveness of the proposed algorithm is demonstrated through experiments on three public datasets.

Enhanced Electrochemical Performance and Cycling Stability of the (NH4)8[VIV12VV7O41(OH)9]·11H2O Cathode in Aqueous Zinc Ion Batteries.

Although vanadium-based compounds possess several advantageous characteristics, such as multivalency, open structure, and high theoretical specific capacity, which render them highly promising candidates for cathode materials in aqueous zinc ion batteries (AZIBs), their large-scale application still necessitates addressing the challenges posed by slow kinetics resulting from low conductivity and capacity degradation caused by material dissolution. Therefore, we have successfully synthesized high-purity mixed multivalent (NH4)8[VIV12VV7O41(OH)9]·11H2O (NVO) crystalline materials via a liquid-phase precipitation modulation method and employed it as an innovative AZIB cathode material for the first time. It exhibits a remarkable reversible specific capacity of 240 and 102.2 mAh g-1 after undergoing 1000 cycles at current densities of 1 and 5 A g-1, respectively, highlighting its exceptional cycling stability and electrochemical performance. The results from cyclic voltammetry (CV) and GITT tests demonstrate that the dominant factor influencing the charge storage is the pseudocapacitive behavior, which is accompanied by an exceptionally high diffusion coefficient of Zn2+ at a rate of 10-10 cm2 s-1. The highly reversible intercalation-deintercalation of Zn2+ in NVO/Zn cells is demonstrated through ex-situ TEM, XRD, and XPS analyses. This work provides a benchmark for the development of high-performance POV electrode materials.

Psychological Distress and the Needs of Family Members of Critically Ill Patients in Emergency Departments During the COVID-19 Pandemic: A Cross-Sectional Study.

INTRODUCTION: The literature highlights the importance of the needs of family members of critical patients in emergency departments. Understanding these needs helps to alleviate psychological distress and contribute to the patients' recoveries. This study aimed to examine the psychological distress and needs of family members of critical patients in emergency departments. METHODS: A cross-sectional design was used to collect data using the Depression, Anxiety, and Stress Scale-21, the Critical Care Family Needs Inventory for the Emergency Department, and the Needs Met Inventory questionnaire from a convenience sample of 170 family members of critical patients. Descriptive analysis and importance-performance analysis were applied to analyze the data. RESULTS: The results showed that 52.4% of family members reported mild to extremely severe levels of depression, 60% reported mild to extremely severe levels of anxiety, and 53.5% had mild to extremely severe levels of stress. Anxiety showed a significant negative correlation with comfort needs (r = -0.17) and support needs being met (r = -0.16). The importance-performance analysis showed that the coordinates for support needs were in quadrant IV, signifying a higher level of importance perceived by family members but a lower level of the needs being met. CONCLUSION: Providing the assessment and necessary support to alleviate psychological distress will help enhance the ability of the emergency department to meet families' needs.

Antifouling and antimicrobial wearable electrochemical sweat sensors for accurate dopamine monitoring based on amyloid albumin composite hydrogels.

Wearable electrochemical sweat sensors are potentially promising for health monitoring in a continuous and non-invasive mode with high sensitivity. However, due to the complexity of sweat composition and the growth of skin bacteria, the wearable sweat sensors may gradually lose their sensitivity or even fail over time. To deal with this issue, herein, we proposed a new strategy to construct wearable sweat sensors with antifouling and antimicrobial capabilities. Amyloid albumin hydrogels (ABSAG) were doped with two-dimensional (2D) nanomaterial MXene and CeO2 nanorods to obtain the antifouling and antimicrobial amyloid albumin composite hydrogels (ABSACG, CeO2/MXene/ABSAG), and the wearable sensors were prepared by modifying flexible screen-printed electrodes with the ABSACG. Within this sensing system, the hydrophilic ABSAG possesses strong hydration capability, and it can form a hydration layer on the electrode surface to resist biofouling in sweat. The 2D nanomaterial MXene dispersed in the hydrogel endows the hydrogel with good conductivity and electrocatalytic capability, while the doping of CeO2 nanorods further improves the electrocatalytic performance of the hydrogel and also provides excellent antimicrobial capability. The designed wearable electrochemical sensors based on the ABSACG demonstrated satisfying antifouling and antimicrobial abilities, and they were capable of detecting dopamine accurately in human sweat. It is expected that wearable sensors utilizing the antifouling and antimicrobial ABSACG may find practical applications in human body fluids analysis and health monitoring.

Pan­cancer analysis on the role of KMT2C expression in tumor progression and immunotherapy.

Histone lysine N-methyltransferase 2C (KMT2C) is involved in transcriptional regulation and DNA damage repair. Mutations in KMT2C have been implicated in the progression, metastasis, and drug resistance of multiple cancer types. However, the roles of KMT2C in the regulation of tumor prognosis, immune cell infiltration and the immune microenvironment in these multiple cancer types remain unclear. Therefore, in the present study, data from The Cancer Genome Atlas and Genotype-Tissue Expression databases were used for KMT2C expression analyses. Kaplan-Meier and univariate Cox regression analyses were also performed to investigate the prognostic role of KMT2C. In addition, Gene Set Enrichment Analysis (GSEA) was conducted to study the KMT2C-related signaling pathways. Tumor immune estimation resource 2 and single-sample GSEA were conducted to investigate the correlation between KMT2C expression and immune cell infiltrations, and Spearman's analysis was conducted to study the correlations among KMT2C, tumor mutational burden, microsatellite instability, immune regulators, chemokines and immune receptors. Immunohistochemistry of patient kidney tumor samples was performed to verify the correlation between KMT2C and programmed death-ligand 1 (PD-L1) expression. Finally, RNA interference, wound healing and colony formation assays were conducted to evaluate the effects of KMT2C expression on cell proliferation and metastasis. The results of the present study demonstrated that KMT2C was highly expressed in multiple cancer types, was a protective factor in kidney renal clear cell carcinoma and ovarian serous cystadenocarcinoma, and a risk factor for lung squamous cell carcinoma and uveal melanoma. In addition, KMT2C levels were negatively correlated with immune-activated pathways and the infiltration of immune cells, and positively correlated with inhibitory immune factors and tumor angiogenesis. Patients with low KMT2C expression had higher objective response rates to immunotherapy, and drug sensitivity analysis indicated that topoisomerase, histone deacetylase, DOT1-like histone H3K79 methyltransferase and G9A nuclear histone lysine methyltransferase inhibitors could potentially be used to treat tumors with high KMT2C expression levels. Finally, the KMT2C and PD-L1 expression levels were shown to be positively correlated, and KMT2C knockdown markedly promoted the proliferation and invasion capacities of A549 cells. In conclusion, the present study revealed that low KMT2C expression may be a promising biomarker for predicting the response of patients with cancer to immunotherapy. Conversely, high KMT2C expression was shown to promote tumor angiogenesis, which may contribute to the formation of the immunosuppressive tumor microenvironment.

Three-dimensional visualization technology for guiding one-step percutaneous transhepatic cholangioscopic lithotripsy for the treatment of complex hepatolithiasis.

BACKGROUND: Biliary stone disease is a highly prevalent condition and a leading cause of hospitalization worldwide. Hepatolithiasis with associated strictures has high residual and recurrence rates after traditional multisession percutaneous transhepatic cholangioscopic lithotripsy (PTCSL). AIM: To study one-step PTCSL using the percutaneous transhepatic one-step biliary fistulation (PTOBF) technique guided by three-dimensional (3D) visualization. METHODS: This was a retrospective, single-center study analyzing, 140 patients who, between October 2016 and October 2023, underwent one-step PTCSL for hepatolithiasis. The patients were divided into two groups: The 3D-PTOBF group and the PTOBF group. Stone clearance on choledochoscopy, complications, and long-term clearance and recurrence rates were assessed. RESULTS: Age, total bilirubin, direct bilirubin, Child-Pugh class, and stone location were similar between the 2 groups, but there was a significant difference in bile duct strictures, with biliary strictures more common in the 3D-PTOBF group (P = 0.001). The median follow-up time was 55.0 (55.0, 512.0) days. The immediate stone clearance ratio (88.6% vs 27.1%, P = 0.000) and stricture resolution ratio (97.1% vs 78.6%, P = 0.001) in the 3D-PTOBF group were significantly greater than those in the PTOBF group. Postoperative complication (8.6% vs 41.4%, P = 0.000) and stone recurrence rates (7.1% vs 38.6%, P = 0.000) were significantly lower in the 3D-PTOBF group. CONCLUSION: Three-dimensional visualization helps make one-step PTCSL a safe, effective, and promising treatment for patients with complicated primary hepatolithiasis. The perioperative and long-term outcomes are satisfactory for patients with complicated primary hepatolithiasis. This minimally invasive method has the potential to be used as a substitute for hepatobiliary surgery.

Failure risk management: adaptive performance control and mission abort decisions.

The failure behavior of safety-critical systems typically depends on the system performance level, which offers opportunities to control system failure risk through dynamic performance adjustment. Moreover, mission abort serves as an intuitive way to mitigate safety hazards during mission execution. Our study focuses on systems that execute successive missions with random durations. To balance mission completion probability and system failure risk, we examine two decision problems: when to abort missions and how to select the performance level prior to mission abort. Our objective is to maximize the expected revenue through dynamic performance control and mission abort (PCMA) decisions. We consider condition-based PCMA decisions and formulate the joint optimization problem into a Markov decision process. We establish the monotonicity and concavity of the value function. Based on this insight, we show that optimizing the mission abort policy requires a series of control limits. In addition, we provide conditions under which the performance control policies are monotone. For comparative purposes, we analytically evaluate the performances of some heuristic policies. Finally, we present a case study involving unmanned aerial vehicles executing power line inspections. The results indicate the superiority of our proposed risk control policies in enhancing operational performance for safety-critical systems. Dynamic performance adjustment and mission abort decisions provide opportunities to reduce the failure risk and increase operational rewards of safety-critical systems.

Monocarboxylate transporter 4 facilitates Mycobacterium tuberculosis survival through NF-κB p65-mediated interleukin-10 production.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, with the highest single-cause mortality. Monocarboxylate transporter 4 (Mct4) transports intracellular lactate outside, but its role in regulating host immune response against Mtb infection remains unknown. Mct4 expression was upregulated in Mtb-infected macrophages and in patients with TB. Mct4 silencing/deficiency significantly decreased Mtb survival in macrophages and in lungs and spleens of mice, while Mct4 overexpression facilitated Mtb survival in macrophages. Furthermore, Mct4 promoted intracellular lactate transport, nuclear factor κB (NF-κB) p65 activation, and interleukin-10 (IL-10) production upon Mtb infection. Mechanistically, IL-10 silencing and IL-10-neutralizing antibody blocked Mct4 overexpressing increased Mtb survival. Replenishing lactate and NF-κB p65 inhibitor JSH23 treatment could inhibit Mct4 overexpressing increased NF-κB p65 activation, IL-10 production, and Mtb survival in macrophages. This study demonstrates that Mct4 promotes Mtb survival through restricting intracellular lactate accumulation to promote NF-κB p65-mediated IL-10 production and suggests Mct4-NF-κB p65-IL-10 axis a potential target for TB treatment.

HARMONIZE Asia: A Phase III Randomized Study to Investigate the Efficacy and Safety of Sodium Zirconium Cyclosilicate in Patients with Hyperkalemia in China.

PURPOSE: Sodium zirconium cyclosilicate (SZC) is an oral potassium (K+)-lowering therapy for adults with hyperkalemia. HARMONIZE Asia (ClinicalTrials.gov identifier: NCT03528681) evaluated the efficacy and safety of SZC in Chinese patients with hyperkalemia. METHODS: This Phase III, randomized, double-blind, placebo-controlled study recruited patients with serum K+ (sK+) ≥5.1 mmol/L at 35 sites in China. Patients received SZC 10 g three times daily (TID) for 24 or 48 hours during an open-label initial phase (OLP). Those patients achieving normokalemia (sK+ 3.5-5.0 mmol/L inclusive) entered a 28-day randomized (2:2:1) treatment phase (RTP) and received SZC 5 g, SZC 10 g, or placebo once daily. The primary endpoint was mean sK+ during RTP Days 8 to 29. Secondary endpoints included mean change in sK+ during the OLP, the proportion of patients who achieved normokalemia at the end of the OLP, the proportion that maintained normokalemia during the RTP, and time to recurrence of hyperkalemia. FINDINGS: In total, 270 patients received SZC 10 g TID during the OLP; 256 (94.8%) completed the OLP. During the OLP, mean sK+ decreased by 1.1 mmol/L from baseline (5.9 mmol/L; P < 0.001) and 87.4% of patients achieved normokalemia. During the RTP, SZC 5 g and 10 g reduced mean sK+ versus placebo in a dose-dependent manner (each P < 0.001); least-squares means (95% confidence interval [CI]) sK+ were 4.9 mmol/L (4.7, 5.0), 4.4 mmol/L (4.3, 4.6), and 5.2 mmol/L (5.1, 5.4) for SZC 5 g, 10 g, and placebo, respectively. At RTP end, the proportions of patients who maintained normokalemia were 58.8% (SZC 5 g; odds ratio vs placebo, 2.5 [95% CI: 1.1, 6.1; P = 0.035]), 76.5% (SZC 10 g; odds ratio vs placebo, 6.3 [95% CI: 2.6, 15.3; P < 0.001]), and 36.8% for placebo. Risk of recurrent hyperkalemia was reduced by 61.0% and 84.0% with SZC 5 g and SZC 10 g, respectively, versus placebo (each P < 0.001). During the RTP, the incidence of adverse events was numerically higher with SZC 5 g (50.0% of patients) and 10 g (44.0%) versus placebo (36.0%); driven primarily by peripheral edema and constipation. IMPLICATIONS: Both SZC doses demonstrated clinically relevant and statistically significant, dose-dependent efficacy in managing sK+ levels in Chinese patients with hyperkalemia, compared with placebo. SZC tolerability was broadly aligned with the known safety profile of SZC.

Development and validation of novel interpretable survival prediction models based on drug exposures for severe heart failure during vulnerable period.

BACKGROUND: Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period. METHODS: We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values. RESULTS: A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality. CONCLUSIONS: The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively.

Synthesis of shape-controlled covalent organic frameworks for light scattering detection of iron and chromium ions.

Fabricating covalent organic frameworks with different morphologies based on the same structural motifs is both interesting and challenging. Here, a TTA-TFP-COF was synthesized by both solvothermal and room temperature methods, with 2,4,6-Tris(4-aminophenyl)-1,3,5-triazine (TTA) and 1,3,5-tris(4-formylphenyl)-benzene (TFP) as raw material. Using different synthesis conditions and adding aniline and benzaldehyde as regulators in the synthesis process, we found that these processes could slow down the reaction speed, increase the exchange and metathesis reactions of dynamic reversible reactions, and improve the reversibility of the reaction system. Thus, controllable synthesis of TTA-TFP-COF with different morphologies, including micro-particles, hollow tubes with controllable diameters, and micro-flowers was achieved. Our further study found that metal ions, Fe3+ and Cr3+ ions, could coordinate with N and O in TTA-TFP-COF and partially destroy the structure of TTA-TFP-COF. The particle size of the TTA-TFP-COF became smaller, thus resulting in the decrease of the light scattering intensity of the COF. An excellent linear relationship exists between the light scattering changes (ΔI) and metal ions concentration (c) from 2.0 to 350.0 µM for Fe3+ and 40.0-800.0 µM for Cr3+, respectively. Thus, rapid and selective analytical methods for detecting metal ions were developed by TTA-TFP-COF here.

Tuberculosis in infertility and in vitro fertilization-embryo transfer.

ABSTRACT: Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

The Brain-Gut-Bone Axis in Neurodegenerative Diseases: Insights, Challenges, and Future Prospects.

Neurodegenerative diseases are global health challenges characterized by the progressive degeneration of nerve cells, leading to cognitive and motor impairments. The brain-gut-bone axis, a complex network that modulates multiple physiological systems, has gained increasing attention owing to its profound effects on the occurrence and development of neurodegenerative diseases. No comprehensive review has been conducted to clarify the triangular relationship involving the brain-gut-bone axis and its potential for innovative therapies for neurodegenerative disorders. In light of this, a new perspective is aimed to propose on the interplay between the brain, gut, and bone systems, highlighting the potential of their dynamic communication in neurodegenerative diseases, as they modulate multiple physiological systems, including the nervous, immune, endocrine, and metabolic systems. Therapeutic strategies for maintaining the balance of the axis, including brain health regulation, intestinal microbiota regulation, and improving skeletal health, are also explored. The intricate physiological interactions within the brain-gut-bone axis pose a challenge in the development of effective treatments that can comprehensively target this system. Furthermore, the safety of these treatments requires further evaluation. This review offers a novel insights and strategies for the prevention and treatment of neurodegenerative diseases, which have important implications for clinical practice and patient well-being.

An endothelium membrane mimetic antithrombotic coating enables safer and longer extracorporeal membrane oxygenation application.

Thrombosis and plasma leakage are two of the most frequent dysfunctions of polypropylene (PP) hollow fiber membrane (PPM) used in extracorporeal membrane oxygenation (ECMO) therapy. In this study, a superhydrophilic endothelial membrane mimetic coating (SEMMC) was constructed on polydopamine-polyethyleneimine pre-coated surfaces of the PPM oxygenator and its ECMO circuit to explore safer and more sustainable ECMO strategy. The SEMMC is fabricated by multi-point anchoring of a phosphorylcholine and carboxyl side chained copolymer (PMPCC) and grafting of heparin (Hep) to form PMPCC-Hep interface, which endows the membrane superior hemocompatibility and anticoagulation performances. Furthermore, the modified PPM reduces protein adsorption amount to less than 30 ng/cm2. More significantly, the PMPCC-Hep coated ECMO system extends the anti-leakage and non-clotting oxygenation period to more than 15 h in anticoagulant-free animal extracorporeal circulation, much better than the bare and conventional Hep coated ECMO systems with severe clots and plasma leakage in 4 h and 8 h, respectively. This SEMMC strategy of grafting bioactive heparin onto bioinert zwitterionic copolymer interface has great potential in developing safer and longer anticoagulant-free ECMO systems. STATEMENT OF SIGNIFICANCE: A superhydrophilic endothelial membrane mimetic coating was constructed on surfaces of polypropylene hollow fiber membrane (PPM) oxygenator and its ECMO circuit by multi-point anchoring of a phosphorylcholine and carboxyl side chain copolymer (PMPCC) and grafting of heparin (Hep). The strong antifouling nature of the PMPCC-Hep coating resists the adsorption of plasma bio-molecules, resulting in enhanced hemocompatibility and anti-leakage ability. The grafted heparin on the zwitterionic PMPCC interface exhibits superior anticoagulation property. More significantly, the PMPCC-Hep coating achieves an extracorporeal circulation in a pig model for at least 15 h without any systemic anticoagulant. This endothelial membrane mimetic anticoagulation strategy shows great potential for the development of safer and longer anticoagulant-free ECMO systems.

[Report of a child with Bainbridge-Ropers syndrome due to a novel variant of ASXL3 gene and a literature review].

OBJECTIVE: To explore the clinical phenotype and genetic basis of a child with Bainbridge-Ropers syndrome (BRPS). METHODS: A child with BRPS who had visited Nanjing Children's Hospital on June 26, 2019 was selected as the study subject. Clinical data of the child was reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child was a 6-month-old girl with peculiar facial features, feeding difficulties, malnutrition, global developmental delay, hypotonia, mildly elevated aminotransferase and ulnar deviation. Results of WES showed that she has harbored a c.1533_1534del variant of the ASXL3 gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. No similar case had been retrieved from the HGMD and ClinVar databases. No frequency for this variant among Asian populations was available in the ExAC, 1000 Genomes, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1533_1534del variant of the ASXL3 gene was determined to be likely pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The ASXL3 gene c.1533_1534del variant probably underlay the BRPS in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling for children with similar disorders.

Jin-Xin-Kang alleviates heart failure by mitigating mitochondrial dysfunction through the Calcineurin/Dynamin-Related Protein 1 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic heart failure (CHF) is a severe consequence of cardiovascular disease, marked by cardiac dysfunction. Jin-Xin-Kang (JXK) is a traditional Chinese herbal formula used for the treatment of CHF. This formula consists of seven medicinal herbs, including Ginseng (Ginseng quinquefolium (L.) Alph.Wood), Astragali Radix (Astragalus membranaceus (Fisch.) Bunge), Salvia miltiorrhiza (Salvia miltiorrhiza Bunge), Descurainiae Semen Lepidii Semen (Descurainia sophia (L.) Webb ex Prantl), Leonuri Herba (Leonurus japonicus Houtt.), Cinnamomi Ramulus (Cinnamomum cassia (L.) J.Presl), and Ilex pubescens (Ilex pubescens Hook. & Arn.). Its clinical efficacy has been validated through prospective randomized controlled studies. However, the specific mechanisms of action for this formula have yet to be elucidated. AIM OF THE STUDY: This study aimed to investigate the effect of JXK on mitochondrial function and its mechanism in the treatment of CHF. METHODS: JXK components were qualitatively analyzed using UPLC-Q-Orbitrap-MS. HF was induced in mice via transverse aortic constriction (TAC). After successful model establishment, lyophilized JXK-L (4.38 g/kg) and JXK-H (13.14 g/kg) were administered for 8 weeks. In vitro, hypertrophic myocardium was induced using angiotensin II (Ang II) for 48 h, followed by JXK-L and JXK-H treatment. Network pharmacology and molecular docking techniques were used to predict the relevant targets of JXK. Cardiac function, serum markers, and histopathological changes were evaluated to assess cardiac function. Immunofluorescence of Tomm20, mitochondrial membrane potential, and ROS were measured to assess mitochondrial dysfunction. Protein expression of calcineurin (CaN) and Drp1 in the myocardium was assessed by Western blot analysis. RESULTS: We detected that the active components of JXK include terpenes, glycosides, flavonoids, amino acids, and alkaloids, among others. In mice with CHF, JXK improved cardiac function and reversed ventricular remodeling. Network pharmacology indicated that JXK can inhibit the calcium signaling pathway. The molecular docking results demonstrated that the active components of JXK effectively bind with CaN. Both in vitro and in vivo experiments confirmed that JXK regulated the CaN/Drp1 pathway and alleviated mitochondrial dysfunction. CONCLUSION: JXK can inhibit the CaN/Drp1 pathway to improve mitochondrial function, and consequently treat CHF.