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SARS-CoV-2 rebound and post-acute mortality and hospitalization among patients admitted with COVID-19: cohort study
Abstract Recent investigations have demonstrated a relationship between the persistence of SARS-CoV-2 and post-COVID-19 conditions. Building upon a potential connection between SARS-CoV-2 persistence and early virologic rebound, we examine the association of early virologic rebound with post-acute mortality and hospitalization due to post-acute sequelae among hospitalized patients with COVID-19 in Hong Kong. Our study includes 13,859, 3959, and 4502 patients in the all-patient, nirmatrelvir/ritonavir, and molnupiravir group, respectively. Results show that patients who experienced virologic rebound exhibited a significantly higher risk of post-acute mortality (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.36–1.70) with a risk difference [RD] of 7.19%, compared with patients without virologic rebound. A similar increase in the risk of post-acute mortality is also observed in nirmatrelvir/ritonavir-treated patients (HR, 1.78; 95% CI, 1.41–2.25; RD, 12.55%) and molnupiravir-treated patients (HR, 1.47; 95% CI, 1.18–1.82; RD, 4.90%). The virologic rebound may thus serve as an early marker for post-COVID-19 condition, enabling healthcare officials to monitor and provide timely intervention for long COVID.
Assessing the biomechanics of scheuermann’s kyphosis affected thoracolumbar spine in forward flexion at the tissue-level using a finite element model
Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst
Abstract Studies in the mouse demonstrate the importance of fibroblast growth factor (FGF) and extra-cellular receptor tyrosine kinase (ERK) in specification of embryo-fated epiblast and yolk-sac-fated hypoblast cells from uncommitted inner cell mass (ICM) cells prior to implantation. Molecular mechanisms regulating specification of early lineages in human development are comparatively unclear. Here we show that exogenous FGF stimulation leads to expanded hypoblast molecular marker expression, at the expense of the epiblast. Conversely, we show that specifically inhibiting ERK activity leads to expansion of epiblast cells functionally capable of giving rise to naïve human pluripotent stem cells. Single-cell transcriptomic analysis indicates that these epiblast cells downregulate FGF signalling and maintain molecular markers of the epiblast. Our functional study demonstrates the molecular mechanisms governing ICM specification in human development, whereby segregation of the epiblast and hypoblast lineages occurs during maturation of the mammalian embryo in an ERK signal-dependent manner.
Development of tetraculture spheroids as a versatile 3D model for personalized breast cancer research
Abstract The tumor microenvironment (TME) plays a pivotal role in cancer progression and drug resistance, influenced by the interaction of tumor cells with surrounding fibroblasts, immune, and endothelial cells. Developing robust multicellular tumor spheroids (MCTSs) that mimic the tumor microenvironment is crucial for studying cancer progression and therapeutic resistance. This study aimed to establish a reproducible method for generating MCTSs using a tetraculture system in four breast cancer cell lines: BT474, T47D, MDA-MB-231, and SK-BR-3. This approach incorporates primary cancer-associated fibroblasts (CAFs), macrophages (THP-1), and endothelial cells (Ea.hy926) alongside the cancer cells. MCTSs were generated using a simple method on ultra-low attachment plates, ensuring spheroid viability and uniformity across cell lines, confirmed by immunofluorescence and immunohistochemistry. MCTSs underwent extensive characterization, including invasion pattern analysis, macrophage polarization potential, cytotoxicity assay to assess chemotherapeutic resistance, and gene expression analysis to explore extracellular matrix (ECM) remodeling. The spheroids exhibited distinct morphologies, growth patterns, and cell distributions, reflecting unique microenvironment interactions and providing a reliable platform for studying TME. This versatile 3D model offers a promising platform for personalized therapy design, as it enables the incorporation of patient-derived cells regardless of tumor phenotype or inter-patient variability. Including key elements of the tumor microenvironment supports individualized drug testing and functional analysis, serving as a reproducible and ethically favorable alternative to animal models and patient-derived explants.
A SaBOX/Co catalyst designed for facile access to the challenging copolymers of vinyl ester and methacrylate
Topological modeling and QSPR based prediction of physicochemical properties of bioactive polyphenols
A dedicated skin-to-brain circuit for cool sensation in mice
Effect of spironolactone on monocyte subsets in atrial fibrillation: IMPRESS-AF randomised controlled trial
Abstract Background Monocyte subsets differentially influence pathophysiology of heart failure and atrial fibrillation (AF) through inflammation, fibrosis, and angiogenesis. Spironolactone has antifibrotic properties. This study investigated the effect spironolactone on monocyte subsets and monocyte effects for peak oxygen consumption (peakVO2), diastolic function and brain natriuretic peptide (BNP) in the IMPRESS-AF randomised controlled trial population (2-year treatment with spironolactone 25 mg vs placebo). Methods CD14++CD16-CCR2+(Mon1), CD14++CD16+CCR2+(Mon2) and CD14+CD16++CCR2-(Mon3) monocyte subsets were analysed by flow cytometry and compared between spironolactone and placebo groups at 12 months and 24 months after randomisation. PeakVO2, diastolic function (echocardiographic E/'e) and BNP were measured at baseline and 24 months. Linear regression was used to assess the effects of monocytes on the outcomes (Python 3.10 modules). Results Monocyte data were available in 225 (90%) IMPRESS-AF patients (age 72[67-77], 78% male). At 12-month the spironolactone group had fewer Mon3 (50[36-74] vs 60[44-90] cells/microL, p=0.02), and lower CD14 expression on Mon1 (1.37[1.17-1.59] vs 1.48[1.24-1.70], p=0.04); no difference remained by 24 months (p>0.05). A high 12-month Mon1 count independently predicted lower E/e’ at 24 months (p=0.02). Conclusions Spironolactone temporarily reduced proinflammatory monocyte markers (Mon3 count and CD14 expression on Mon1). Mon1 may have a positive effect on diastolic dysfunction in AF.
Inhibition of HDAC6 alters fumarate hydratase activity and mitochondrial structure
Abstract Fumarate hydratase (FH), a key node of mitochondrial metabolism, is also a tumour suppressor. Despite its prominent roles in tumourigenesis and inflammation, its regulation remains poorly understood. Herein, we show that histone deacetylase 6 (HDAC6) regulates FH activity. In triple-negative breast cancer cells, HDAC6 inhibition or knockdown results in alterations to mitochondrial cristae structure, as detected by live-cell super-resolution STED nanoscopy and electron microscopy, along with the release of mitochondrial DNA. Mass-spectrometry immunoprecipitation reveals multiple mitochondrial HDAC6-interactors, with FH emerging as a top hit. Super-resolution 3D-STORM shows HDAC6 interactions with FH in mitochondrial networks, which increases after perturbation of HDAC6 activity with BAS-2. Treatment with BAS-2 leads to fumarate accumulation by 13C glucose labelling, along with downstream succination of proteins and cell death. Together, these results identify HDAC6 inhibition as a regulator of endogenous FH activity in tumour cells, and highlight it as a promising candidate for indirectly targeting tumour metabolism.
Effects of Scutellaria baicalensis, Folium Artemisiae argyi, and Galla Chinensis on the protein expression and resistance genes of Exiguobacterium sp. in response to gentamicin
DynaTag for efficient mapping of transcription factors in low-input samples and at single-cell resolution
Abstract Systematic discovery of transcription factor (TF) landscapes in low-input samples and at single cell level is a major challenge in the fields of molecular biology, genetics, and epigenetics. Here, we present cleavage under Dyna mic targets and Tag mentation (DynaTag), enabling robust mapping of TF-DNA interactions using a physiological salt solution during sample preparation. DynaTag uncovers occupancy alterations for 15 TFs in stem cell and cancer tissue models. We highlight changes in TF-DNA binding for NANOG, MYC, and OCT4, during stem-cell differentiation, at both bulk and single-cell resolutions. DynaTag surpasses CUT&RUN and ChIP-seq in signal-to-background ratio and resolution. Furthermore, using tumours of a small cell lung cancer model derived from a single female donor, DynaTag reveals increased chromatin occupancy of FOXA1, MYC, and the mutant p53 R248Q at enriched gene pathways (e.g. epithelial-mesenchymal transition), following chemotherapy treatment. Collectively, we believe that DynaTag represents a significant technological advancement, facilitating precise characterization of TF landscapes across diverse biological systems and complex models.
Single-quantum sodium MRI at 3 T for separation of mono- and bi-T2 sodium signals
Biomechanical control of vascular morphogenesis by the surrounding stiffness
Abstract Sprouting angiogenesis is a form of morphogenesis which expands vascular networks from preexisting networks. However, the precise mechanism governing efficient branch elongation driven by directional movement of endothelial cells (ECs), while the lumen develops under the influence of blood inflow, remains unknown. Herein, we show perivascular stiffening to be a major factor that integrates branch elongation and lumen development. The lumen expansion seen during lumen development inhibits directional EC movement driving branch elongation. This process is counter-regulated by the presence of pericytes, which induces perivascular stiffening by promoting the deposition of EC-derived collagen-IV (Col-IV) on the vascular basement membrane (VBM), thereby preventing excessive lumen expansion. Furthermore, inhibition of forward directional movement of the tip EC during lumen development is associated with decreased localization of the F-BAR proteins and Arp2/3 complexes at the leading front. Our results demonstrate how ECs elongate branches, while the lumen develops, by properly building the surrounding physical environment in coordination with pericytes during angiogenesis.
Classification of skin diseases with deep learning based approaches
3D bioprinting of plant and animal cell-based hybrid food
Optimizing intelligent reflecting surface assisted visible light communication networks under blockage and practical constraints using TLBO for IoT applications
Nitrogen heterocyclic covalent organic frameworks for efficient H2O2 photosynthesis and in situ water treatment
Targeting oxidative stress and metal imbalance in cerebral ischemia: the neuroprotective role of sodium valproate
Accelerating lithium-mediated nitrogen reduction through an integrated palladium membrane hydrogenation reactor
Abstract Lithium-mediated N2 reduction reaction (LiNRR) is regarded as the most robust route towards electrifying NH3 synthesis. However, in this reaction geometry, hydrogen atoms typically supplied through electrolyte degradation, via H2 oxidation or a combination of both, hampering the efficiency of the process. In this work we provide an alternative H-source by merging a Pd Membrane reactor (PMR) with a LiNRR reactor in a unique dual-reactor setup. Specifically, use a Pd membrane that extracts H atoms directly from H2O and transfers them across the membrane to an electrodeposited Li layer operating under non-aqueous LiNRR conditions. We show that these H2O-derived H-atoms are used directly to synthesize NH3 in the presence of N2 and electrodeposited Li, thereby opening orthogonal reaction pathways within the metal-mediated nitrogen reduction concept.