A randomized trial comparing a 5-day course of intravenous remdesivir with a 10-day course in patients with Covid-19 pneumonia and hypoxemia who were not yet receiving mechanical ventilation showed ...no significant differences in outcome related to the duration of treatment.
Increasing reports on epidemiological, diagnostic, and clinical studies suggest that dysfunction of the inflammatory reaction results in chronic illnesses such as cancer, arthritis, arteriosclerosis, ...neurological disorders, liver diseases, and renal disorders. Chronic inflammation might progress if injurious agent persists; however, more typically than not, the response is chronic from the start. Distinct to most changes in acute inflammation, chronic inflammation is characterized by the infiltration of damaged tissue by mononuclear cells like macrophages, lymphocytes, and plasma cells, in addition to tissue destruction and attempts to repair. Phagocytes are the key players in the chronic inflammatory response. However, the important drawback is the activation of pathological phagocytes, which might result from continued tissue damage and lead to harmful diseases. The longer the inflammation persists, the greater the chance for the establishment of human diseases. The aim of this review was to focus on advances in the understanding of chronic inflammation and to summarize the impact and involvement of inflammatory agents in certain human diseases.
Chronic inflammation is a greater the chance for the establishment of human diseases.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
A phase transition is often accompanied by the appearance of an order parameter and symmetry breaking. Certain magnetic materials exhibit exotic hidden-order phases, in which the order ...parameters are not directly accessible to conventional magnetic measurements. Thus, experimental identification and theoretical understanding of a hidden order are difficult. Here we combine neutron scattering and thermodynamic probes to study the newly discovered rare-earth triangular-lattice magnet TmMgGaO
4
. Clear magnetic Bragg peaks at K points are observed in the elastic neutron diffraction measurements. More interesting, however, is the observation of sharp and highly dispersive spin excitations that cannot be explained by a magnetic dipolar order, but instead is the direct consequence of the underlying multipolar order that is “hidden” in the neutron diffraction experiments. We demonstrate that the observed unusual spin correlations and thermodynamics can be accurately described by a transverse field Ising model on the triangular lattice with an intertwined dipolar and ferro-multipolar order.
Quantum spin liquids (QSLs) are exotic states of matter characterized by emergent gauge structures and fractionalized elementary excitations. The recently discovered triangular lattice ...antiferromagnet YbMgGaO4 is a promising QSL candidate, and the nature of its ground state is still under debate. Here we use neutron scattering to study the spin excitations in YbMgGaO4 under various magnetic fields. Our data reveal a dispersive spin excitation continuum with clear upper and lower excitation edges under a weak magnetic field (H = 2.5 T). Moreover, a spectral crossing emerges at the Γ point at the Zeeman-split energy. The corresponding redistribution of the spectral weight and its field-dependent evolution are consistent with the theoretical prediction based on the inter-band and intra-band spinon particle-hole excitations associated with the Zeeman-split spinon bands, implying the presence of fractionalized excitations and spinon Fermi surfaces in the partially magnetized QSL state in YbMgGaO4.
Rare subpopulations of cancer stem cells (CSCs) have the ability to self-renew and are the primary driving force behind cancer metastatic dissemination and the preeminent hurdle to cancer treatment. ...As opposed to differentiated, non-malignant tumor offspring, CSCs have sophisticated metabolic patterns that, depending on the kind of cancer, rely mostly on the oxidation of major fuel substrates such as glucose, glutamine, and fatty acids for survival. Glutaminolysis is a series of metabolic reactions that convert glutamine to glutamate and, eventually, α-ketoglutarate, an intermediate in the tricarboxylic acid (TCA) cycle that provides biosynthetic building blocks. These building blocks are mostly utilized in the synthesis of macromolecules and antioxidants for redox homeostasis. A recent study revealed the cellular and molecular interconnections between glutamine and cancer stemness in the cell. Researchers have increasingly focused on glutamine catabolism in their attempt to discover an effective therapy for cancer stem cells. Targeting catalytic enzymes in glutaminolysis, such as glutaminase (GLS), is achievable with small molecule inhibitors, some of which are in early-phase clinical trials and have promising safety profiles. This review summarizes the current findings in glutaminolysis of CSCs and focuses on novel cancer therapies that target glutaminolysis in CSCs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Tubulin post-translational modifications (PTMs) occur spatiotemporally throughout cells and are suggested to be involved in a wide range of cellular activities. However, the complexity and dynamic ...distribution of tubulin PTMs within cells have hindered the understanding of their physiological roles in specific subcellular compartments. Here, we develop a method to rapidly deplete tubulin glutamylation inside the primary cilia, a microtubule-based sensory organelle protruding on the cell surface, by targeting an engineered deglutamylase to the cilia in minutes. This rapid deglutamylation quickly leads to altered ciliary functions such as kinesin-2-mediated anterograde intraflagellar transport and Hedgehog signaling, along with no apparent crosstalk to other PTMs such as acetylation and detyrosination. Our study offers a feasible approach to spatiotemporally manipulate tubulin PTMs in living cells. Future expansion of the repertoire of actuators that regulate PTMs may facilitate a comprehensive understanding of how diverse tubulin PTMs encode ciliary as well as cellular functions.
Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. We report herein a sonogenetic approach that can manipulate target cell activities by ...focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterologous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also noninvasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mouse brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, our sonogenetic tools will serve as new strategies for noninvasive therapy in deep tissues.
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IJS, KILJ, NUK, PNG, UL, UM
To understand human parechovirus (HPeV) infections in Taiwanese children, we analyzed data for 112 children (age≤10 years) with HPeV infection diagnosed between July 2007 and June 2016 in a medical ...center in Kaohsiung, southern Taiwan. The patients were infected with HPeV1 (n=94), HPeV3 (n=3), HPeV4 (n=3), HPeV6 (n=1) and non-typeable HPeV (n=11). We compared the clinical implications for children younger than 3 months (n=56) and 3 months and older (n=31), excluding 25 children with concomitant infections. Fever was noted in almost half of the children younger than 3 months but was more frequent in older than in younger children (83.9% vs 46.4%). As compared with older children, children younger than 3 months had a lower incidence of respiratory symptoms (30.1% vs 83.9%), more frequently required intensive care unit admission (28.6% vs 3.2%), and had longer hospital stays (mean 10.95 vs 5.13 days). Importantly, about one-third of the children were suspected to have hospital-acquired or cluster infections in the environment of medical institutions, with a significantly high proportion of 42.9% (24/56) in younger infants. Hospital-acquired infections might play a key role in the spread of HPeV, especially in children younger than 3 months.
Dichloroacetic acid (DCAA), one of the disinfection by‐products in water, has showed critical harm to human health since it can cause cancer, teratogen and mutagen. Herein, a quaternized hollow fiber ...membrane was fabricated by ring‐open reaction via a facile one‐step immersion method, which could fast adsorb DCAA by flow‐through adsorption. The obtained membrane with a sponge pore structure, which was quaternized at 60°C in an alkaline solution, exhibited excellent adsorption performance with removal percentage of 100%, life span up to 100 L and treating capacity of 24.8 mg m−2. Meanwhile, the optimal membrane exhibited the exceptional performance in a neutral test solution compared with acid or alkaline test solution. It was concluded that electrostatic attraction between positively charged quaternary ammonium groups and negatively charged DCAA was responsible for the adsorption mechanism. Additionally, fitting results indicated that the adsorption of DCAA onto the membrane was mainly dominated by homogeneous monolayer adsorption. This work developed a facile approach to prepare a novel quaternized membrane with outstanding adsorption performance, which demonstrated huge potentials in the molecular separation and water purification fields.
Flow‐through adsorption process of the membrane.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Blood transfusion (BT) may be associated with an increased risk of thromboembolism. The associations between transfusion reactions (TRs) during BTs and potential risk factors for the ...development of thromboembolism in patients underwent blood transfusion have not been analyzed. Therefore, this study aimed to compare risk factors associated with the development of venous thromboembolism (VTE) or pulmonary embolism (PE) between patients underwent blood transfusion with and without TRs.
Study Designs and Methods
The retrospective study was conducted between April 1, 2017, and March 31, 2020, at a medical center in Taiwan. Blood‐transfused patients were grouped into two cohorts as follows: those who experienced TRs and those who did not experience TRs. Both cohorts were subjected to follow‐up until March 31, 2021. The endpoints for both groups were the occurrence of VTE or PE or the date of March 31, 2021. To investigate between‐cohort risk differences, a Kaplan–Meier survival analysis and multiple Cox proportional hazard model was used.
Results
A total of 10,759 patients underwent 59,385 transfusion procedures, with 703 patients in the TR group, and 10,056 patients in the non‐TR group. The risk of VTE or PE was twice as high in the TR group than in the non‐TR group (adjusted hazard ratio 2.53, 95% confidence interval 1.49–4.29, p = .001). Meanwhile, age, female sex, transfusion frequency increment, and being nondiabetic was associated with an increased risk of developing thromboembolism.
Conclusion
TRs are associated with increased long‐term thromboembolism risk in patients underwent blood transfusion. It is imperative for clinicians to acknowledge this and maintain rigorous follow‐up.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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