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Abstract Severe pulmonary hypertension (PH) is not common even in patients with severe chronic lung disease (CLD) but data on hemodynamic characteristics among patients with severe CLD is scarce. All adult patients who had right heart catheterization for lung transplant assessment for severe CLD in the only lung transplant service and for PAH management in the only tertiary pulmonary hypertension service in Hong Kong from 2010 to 2020 were included and classified into CLD group and PAH group. Patient characteristics and hemodynamic parameters were analyzed. There were 153 patients included with 106 patients in the CLD group and 47 in the PAH group. There were only 19.8% of the patients in the CLD group had severe pulmonary hypertension. Patients in the CLD group had significantly lower systolic pulmonary arterial pressure (PAPs), lower mean pulmonary arterial pressure (PAPm), higher cardiac index, and lower PVR when compared with the PAH group (p

Abstract Transition metal oxides hold great promise for lithium‐ion batteries (LIBs) and electrocatalytic water splitting because of their high abundance and high energy density. However, designing and fabrication of efficient, stable, high power density electrode materials are challenging. Herein, we report rambutan‐like hollow carbon spheres formed by carbon nanosheet decorated with nickel oxide (NiO) rich in metal vacancies (denoted as h‐NiO/C) as a bifunctional electrode material for LIBs and electrocatalytic oxygen evolution reaction (OER). When being used as the anode of LIBs, the h‐NiO/C electrode shows a large initial capacity of 885 mA h g−1, a robust stability with a high capacity of 817 mA h g−1 after 400 cycles, and great rate capability with a high reversible capacity of 523 mA h g−1 at 10 A g−1 after 600 cycles. Moreover, working as an OER electrocatalyst, the h‐NiO/C electrode shows a small overpotential of 260 mV at 10 mA cm−2, a Tafel slope of 37.6 mV dec−1 along with good stability. Our work offers a cost‐effective method for the fabrication of efficient electrode for LIBs and OER.

Objective. To evaluate the possible biological effect of allogenic mesenchymal stem cells (MSCs) combined with tissue fusion technology on the anastomosis. Methods. Sixteen pigs were divided into a 7 d group and 14 d group, each of which was further subdivided into an MSC-treated group and a control group. Five anastomoses per animal were established using LigaSure ForceTriad (Covidien, MA, USA), a tissue sealing system. Cell migration and tissue-specific differentiation potency, in addition to potential cytokine and genetic changes, were investigated. Results. There were no significant between-group differences in postoperative complications and anastomosis burst pressure. The number of proliferating cell nuclear antigen- (PCNA-) positive cells was significantly higher in the MSC-treated group as compared with that in the control group (P=0.021). Labeled MSCs were found in the mucosal layer, villus, and lamina propria, as well as in the lamina muscularis mucosae, where they exhibited characteristics of smooth muscle cells. Conclusions. Grafted MSCs significantly promoted epithelial and connective cell proliferation and maintained their cell migration capacity and differentiation potential in the fused anastomotic tissues, without causing severe postoperative complications.

Background: The Prostate Cancer Prevention Trial (PCPT) was a 7-year randomized, double-blind, placebocontrolled trial of the efficacy of finasteride for the prevention of prostate cancer with a primary outcome of histologically determined prevalence of prostate cancer at the end of 7 years. Methods: A systematic modeling process using logistic regression identified factors available at year 6 that are associated with end-of-study (EOS) biopsy adherence at year 7, stratified by whether participants were ever prompted for a prostate biopsy by year 6. Final models were evaluated for discrimination. At year 6,13,590 men were available for analysis. Results: Participants were more likely to have the EOS biopsy if they were adherent to study visit schedules and procedures and/or were in good health (P < 0.01). Participants at larger sites and/or sites that received retention and adherence grants were also more likely to have the EOS biopsy (P < 0.05). Conclusions: Our results show good adherence to study requirements 1 year before the EOS biopsy was associated with greater odds that a participant would comply with the invasive EOS requirement. Impact: Monitoring adherence behaviors may identify participants at risk of nonadherence to more demanding study end points. Such information could help frame adherence intervention strategies in future trials. © 2014 American Association for Cancer Research.

Background There was a fluctuation in medication demand and supply during COVID-19 pandemic. This study aimed to assess the trend of drug utilisation in Malaysia in 2018–2022 and evaluate the impact of COVID-19 on drug utilisation rates.Methods We conducted a repeated cross-sectional study of pharmaceutical sales data from public and private sectors in Malaysia from 2018 to 2022. Drug utilisation rates for the period after the onset of COVID-19 (2020–2022) was compared with the earlier period (2018–2019). Interrupted time-series regression analyses evaluated level and slope changes compared to pre-COVID-19 pandemic level for quarterly rates of drugs utilisation in public and private sectors.Results There was an immediate reduction in the utilisation rates for all drugs after COVID-19 in public (−20.4%; p = 0.043) and private sectors (−22.4%; p = 0.003). In both sectors, significant level changes were observed for anti-infectives, musculoskeletal, neurological, respiratory, and sensory organs preparations following COVID-19 pandemic, followed by a sustained increase in trend from 2020 to 2022. Public sector had a 22.2% reduction in the utilisation of cardiovascular drugs (p = 0.002), particularly for renin–angiotensin system (RAS) agents (−47.4%, p = 0.019). Private sector had large changes for anti-infectives (−53.6%, p

Abstract Three-dimensional (3D) imaging of thin, extended specimens at nanometer resolution is critical for applications in biology, materials science, advanced synthesis, and manufacturing. One route to 3D imaging is tomography, which requires a tilt series of a local region. However, capturing images at higher tilt angles is infeasible for such thin, extended specimens. Here, we explore a suitable alternative to reconstruct the 3D volume using a single, energy-filtered, bright-field coherent image. We show that when our specimen is homogeneous and amorphous, simultaneously inferring local depth and thickness for 3D imaging is possible in the near-field limit. We demonstrated this technique with a transmission electron microscope to fill a glaring gap for rapid, accessible 3D nanometrology. This technique is applicable, in general, to any coherent bright field imaging with electrons, photons, or any other wavelike particles.

Abstract Current technologies to subtype glioblastoma (GBM), the most lethal brain tumor, require highly invasive brain biopsies. Here, we develop a dedicated analytical platform to achieve direct and multiplexed profiling of circulating RNAs in extracellular vesicles for blood-based GBM characterization. The technology, termed ‘enzyme ZIF-8 complexes for regenerative and catalytic digital detection of RNA’ (EZ-READ), leverages an RNA-responsive transducer to regeneratively convert and catalytically enhance signals from rare RNA targets. Each transducer comprises hybrid complexes – protein enzymes encapsulated within metal organic frameworks – to configure strong catalytic activity and robust protection. Upon target RNA hybridization, the transducer activates directly to liberate catalytic complexes, in a target-recyclable manner; when partitioned within a microfluidic device, these complexes can individually catalyze strong chemifluorescence reactions for digital RNA quantification. The EZ-READ platform thus enables programmable and reliable RNA detection, across different-sized RNA subtypes (miRNA and mRNA), directly in sample lysates. When clinically evaluated, the EZ-READ platform established composite signatures for accurate blood-based GBM diagnosis and subtyping.

Excitotoxicity arises from unusually excessive activation of excitatory amino acid receptors such as glutamate receptors. Following an energy crisis, excitotoxicity is a major cause for neuronal death in neurological disorders. Many glutamate antagonists have been examined for their efficacy in mitigating excitotoxicity, but failed to generate beneficial outcome due to their side effects on healthy neurons where glutamate receptors are also blocked. In this study, we found that during chronic hypoxia there is upregulation and activation of a nonselective cation channel TRPM4 that contributes to the depolarized neuronal membrane potential and enhanced glutamate-induced calcium entry. TRPM4 is involved in modulating neuronal membrane excitability and calcium signaling, with a complex and multifaceted role in the brain. Here, we inhibited TRPM4 using a newly developed blocking antibody M4P, which could repolarize the resting membrane potential and ameliorate calcium influx upon glutamate stimulation. Importantly, M4P did not affect the functions of healthy neurons as the activity of TRPM4 channel is not upregulated under normoxia. Using a rat model of chronic hypoxia with both common carotid arteries occluded, we found that M4P treatment could reduce apoptosis in the neurons within the hippocampus, attenuate long-term potentiation impairment and improve the functions of learning and memory in this rat model. With specificity to hypoxic neurons, TRPM4 blocking antibody can be a novel way of controlling excitotoxicity with minimal side effects that are common among direct blockers of glutamate receptors.

Agriculture in the 21st century faces challenges in adopting efficient and sustainable production methods to feed the growing population. In this context, seaweed offers greater advantages over terrestrial plants. This study investigated the nutritional composition and antioxidant properties of six edible seaweeds found in Malaysia. The seaweeds studied were brown (Padina australis, Sargassum binderi, Sargassum polycystum), green (Caulerpa racemosa, Caulerpa sertularioides), and red (Garcilaria changgi) seaweeds. The moisture, ash, protein, fat, and total dietary fibre contents of the seaweeds were analysed according to the Association of Official Analytical Chemists methods. Total available carbohydrate content was assessed using the Clegg-anthrone method. Mineral, amino acid, and fatty acid contents were determined through atomic absorption spectroscopy, high-performance liquid chromatography, and gas chromatography methods, respectively. Results revealed that the seaweeds were all high in total dietary fibre (53.96–76.97 g/100 g dried weight, dw) and ash (4.46–18.53 g/100 g dw) whereas their fat (0.05–4.62 g/100 g dw) content was generally low. The brown seaweeds were good sources of calcium. Red seaweed G. changii had the highest content of essential amino acids whereas brown seaweed S. binderi had the highest polyunsaturated fatty acid and lowest saturated fatty acid contents. Fucoxanthin could only be detected in brown seaweeds. Methanolic extracts of seaweeds showed good antioxidant activities measured using 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH-RSA), ferric reducing antioxidant power (FRAP), and trolox equivalent antioxidant activity (TEAC) assays. Overall, this study contributed knowledge on underexploited Malaysian seaweeds and proposed them as an alternative source of nutrients for humans to meet food security challenges.

Transition metal oxides hold great promise for lithium‐ion batteries (LIBs) and electrocatalytic water splitting because of their high abundance and high energy density. However, designing and fabrication of efficient, stable, high power density electrode materials are challenging. Herein, we report rambutan‐like hollow carbon spheres formed by carbon nanosheet decorated with nickel oxide (NiO) rich in metal vacancies (denoted as h‐NiO/C) as a bifunctional electrode material for LIBs and electrocatalytic oxygen evolution reaction (OER). When being used as the anode of LIBs, the h‐NiO/C electrode shows a large initial capacity of 885 mA h g−1, a robust stability with a high capacity of 817 mA h g−1 after 400 cycles, and great rate capability with a high reversible capacity of 523 mA h g−1 at 10 A g−1 after 600 cycles. Moreover, working as an OER electrocatalyst, the h‐NiO/C electrode shows a small overpotential of 260 mV at 10 mA cm−2, a Tafel slope of 37.6 mV dec−1 along with good stability. Our work offers a cost‐effective method for the fabrication of efficient electrode for LIBs and OER. [ABSTRACT FROM AUTHOR]

Abstract Due to the growing demand for clean and renewable hydrogen fuel, there has been a surge of interest in electrocatalytic water‐splitting devices driven by renewable energy sources. However, the feasibility of self‐driven water splitting is limited by inefficient connections between functional modules, lack of highly active and stable electrocatalysts, and intermittent and unpredictable renewable energy supply. Herein, we construct a dual‐modulated three‐dimensional (3D) NiCo2O4@NiCo2S4 (denoted as NCONCS) heterostructure deposited on nickel foam as a multifunctional electrode for electrocatalytic water splitting driven by photovoltaic‐powered supercapacitors. Due to a stable 3D architecture configuration, abundant active sites, efficient charge transfer, and tuned interface properties, the NCONCS delivers a high specific capacity and rate performance for supercapacitors. A two‐electrode electrolyzer assembled with the NCONCS as both the anode and the cathode only requires a low cell voltage of 1.47 V to achieve a current density of 10 mA cm−2 in alkaline electrolyte, which outperforms the state‐of‐the‐art bifunctional electrocatalysts. Theoretical calculations suggest that the generated heterointerfaces in NCONCS improve the surface binding capability of reaction intermediates while regulating the local electronic structures, which thus accelerates the reaction kinetics of water electrolysis. As a proof of concept, an integrated configuration comprising a two‐electrode electrolyzer driven by two series‐connected supercapacitors charged by a solar cell delivers a high product yield with superior durability.

Abstract Mouse monoclonal antibody M4M was recently designed to block human TRPM4 channel. The polypeptide for generating M4M is composed of peptide A1 between the transmembrane segment 5 (S5) and the pore, and a second peptide A2 between the pore and the transmembrane segment 6 (S6). Using peptide microarray, a 4-amino acid sequence EPGF within the A2 was identified to be the binding epitope for M4M. Substitution of EPGF with other amino acids greatly reduced binding affinity. Structural analysis of human TRPM4 structure indicates that EPGF is located externally to the channel pore. A1 is close to the EPGF binding epitope in space, albeit separated by a 37-amino acid peptide. Electrophysiological study reveals that M4M could block human TRPM4, but with no effect on rodent TRPM4 which shares a different amino acid sequence ERGS for the binding motif. Our results demonstrate that M4M is a specific inhibitor for human TRPM4.

Atomic-scale insights into how a nanoparticle surface reconstructs under reaction conditions and the impact of the reconstruction on catalytic activity are still lacking. Here the authors reveal that Pd nanocatalysts display oscillatory changes in both their structure and activity during CO oxidation using operando TEM.

Sea cucumber has long been utilized as a treatment for a variety of ailments, including antibacterial, antifungal, immunomodulatory, and wound healing. As for the first time, the extracts of three sea cucumber species’ i.e, Actinopyga lecanora, Holothuria atra, and Stichopus vastus, were compared and tested on the cytotoxicity of cancer cells using MTT and Annexin V/Propidium Iodide assays. This study investigates the protection of sea cucumber extracts against the breast cancer cell line (T-47D). All three extracts were found to be actively declining the cancer cell progression, with the IC50 values of 6.25±0.50 µg/ml (A. lecanora), 7.5 ± 1.39 µg/ml (H. atra) and 3.25 ± 0.53 µg/ml (S. vastus). LC-MS/MS analysis was used to identify chemical compunds in the extracts. The 1,1-diphenyl-2-picrylhydrazyl (DPPH), total phenolic and flavonoid contents, and anti-collagenase activity were also assessed in all the three extracts. The results demonstrated the absence of antioxidant and flavonoid chemicals in S. vastus, A. leconara and H. atra extracts. However, H. atra contained phenolic compounds (0.4794 mgGAE/g DW). Furthermore, all tested extracts showed significant anti-collagenase activity, which supported the reduction of cancer cell proliferation. However, more research into the mechanism of action of the extract is needed before sea cucumbers therapeutic characteristics may be used to combat breast cancer.

Background: The increasing number of reports on cutaneous reactions following COVID-19 vaccination has led to growing concerns among certain groups. Objective: We reviewed the published reports of cutaneous lesions after COVID-19 vaccination. Methods: We conducted a literature search for original and review articles published between January 1, 2020, and September 27, 2021. Results: Eleven cutaneous reactions associated with COVID-19 vaccines were determined; the most prevalent reactions were local injection site reactions, delayed local reactions, urticaria, angioedema, and morbilliform eruptions. There were more reports on skin reactions following the administration of messenger RNA-based vaccines than on those following the administration of adenoviral vector or inactivated whole-virus vaccines, in part, due to their higher administration rate. Most reported skin reactions occurred after the first vaccine dose. Limitations: A reporting bias could not be excluded, and skin biopsy results were not available for most included individuals. Moreover, given that the included trials focused on vaccine efficacy, there was a lack of details concerning cutaneous reactions and participant information. Conclusion: Not all cutaneous reactions observed after COVID-19 vaccination are hypersensitivity reactions. Different cutaneous reactions may reflect underlying immune responses to the vaccines. A large majority of COVID-19 vaccination reactions were mild and self-limiting, and people should be encouraged to complete their vaccination regimen.