Currently, COVID‐19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course and treatment efficacy of COVID‐19 near Hubei ...Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from 20 January to 8 February 2020. Clinical outcomes were followed up until 26 March 2020. The viral shedding duration, full clinical course and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID‐19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS‐CoV‐2. In total, the median SARS‐CoV‐2 shedding period and clinical course were 12 (IQR: 9–17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16–24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively, and ICU patients had longer median viral shedding periods (21 17–24 versus 11 9–15) and clinical courses (30 22–33 vs. 19 15.8–22) than non‐ICU patients (both p < .0001). SARS‐CoV‐2 clearances occurred at least 2 days before fatality in 3 non‐survivors. Current treatment with any anti‐viral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p > .05) in real‐life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current anti‐viral therapies were ineffective for shortening viral shedding duration and clinical course in real‐world settings. These findings expand our knowledge of the SARS‐CoV‐2 infection and may be helpful for management of the epidemic outbreak of COVID‐19 worldwide. Further studies concerning effective anti‐viral agents and vaccines are urgently needed.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
A low-profile wideband stacked tightly coupled patch array (TCPA) with parasitic strips is presented in this brief. Analyzed via a two-port network and originated from the traditional TCPA, the ...evolution of TCPA element is conducted by gradually introducing superstrate, parasitic patch and parasitic strips, and the ultimate one can exhibit an impedance bandwidth of 131.9%. Then, employing a practical feeding structure enables the implementation of the element to operate in a 102.0% band. Eventually, a <inline-formula> <tex-math notation="LaTeX">6\times 6 </tex-math></inline-formula> prototype is constructed to verify the design correctness, and the results reveal that the working band is 2.4-6.8 GHz (94.6%) with VSWR less than 2, while the TCPA can respectively scan from −60° to 60° and from −40° to 40° in the E-plane and H-plane with VSWR<3. On account of its compact size, wide band, ascendant radiation characteristics and scanning performance, the proposed TCPA is promising in the application of large-scale arrays and communication systems.
Erectile dysfunction is now a common disorder of sexual function, and its relationship to dietary calcium, phosphorus, and potassium has not been well studied. We set out to determine if dietary ...intakes of calcium, phosphorus, and potassium are related to erectile dysfunction in U.S. men.
For this cross-sectional investigation, we used data from NHANES 2001-2004. To investigate the connection of dietary calcium, phosphorus, and potassium intake with erectile dysfunction, we employed multivariate logistic regression, smoothed curve fitting, and subgroup analysis.
This cross-sectional study comprised 3,556 eligible male subjects in total, with a weighted mean age of 49.93±18.13 years. After controlling for race and age, the greatest tertile of calcium consumption was found to have a 34% lower risk of erectile dysfunction than the lowest tertile (OR = 0.66; 95% CI = 0.52-0.84; p = 0.0006). The risk of erectile dysfunction was found to be reduced by 33% (OR = 0.67; 95% CI = 0.52-0.87; p = 0.0024) for the highest tertile of phosphorus intake compared to the lowest tertile of phosphorus intake and by 35% (OR = 0.65; 95% CI = 0.50-0.83; p = 0.0006) for the highest tertile of potassium intake compared to the lowest tertile of potassium intake in the fully adjusted model.
Erectile dysfunction and dietary consumption of calcium, phosphorus, and potassium are inversely associated with the U.S. population. To confirm the accuracy of our findings, additional prospective studies are necessary. Furthermore, it is imperative to do further fundamental research at the molecular level to gain a deeper understanding of the underlying mechanisms.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
G-quadruplex (G4) DNA is a type of quadruple helix structure formed by a continuous guanine-rich DNA sequence. Emerging evidence in recent years authenticated that G4 DNA structures exist both in ...cell-free and cellular systems, and function in different diseases, especially in various cancers, aging, neurological diseases, and have been considered novel promising targets for drug design. In this review, we summarize the detection method and the structure of G4, highlighting some non-canonical G4 DNA structures, such as G4 with a bulge, a vacancy, or a hairpin. Subsequently, the functions of G4 DNA in physiological processes are discussed, especially their regulation of DNA replication, transcription of disease-related genes (
c-MYC
,
BCL-
2,
KRAS
,
c-KIT
et al.), telomere maintenance, and epigenetic regulation. Typical G4 ligands that target promoters and telomeres for drug design are also reviewed, including ellipticine derivatives, quinoxaline analogs, telomestatin analogs, berberine derivatives, and CX-5461, which is currently in advanced phase I/II clinical trials for patients with hematologic cancer and BRCA1/2-deficient tumors. Furthermore, since the long-term stable existence of G4 DNA structures could result in genomic instability, we summarized the G4 unfolding mechanisms emerged recently by multiple G4-specific DNA helicases, such as Pif1, RecQ family helicases, FANCJ, and DHX36. This review aims to present a general overview of the field of G-quadruplex DNA that has progressed in recent years and provides potential strategies for drug design and disease treatment.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Recently, perovskite-based light-emitting diodes based on organometal halide emitters have attracted much attention because of their excellent properties of high color purity, tunable emission ...wavelength and a low-temperature processing technique. As is well-known, organic light-emitting diodes have shown powerful capabilities in this field; however, the fabrication of these devices typically relies on high-temperature and high-vacuum processes, which increases the final cost of the product and renders them uneconomical for use in large-area displays. Organic/inorganic hybrid halide perovskites match with these material requirements, as it is possible to prepare such materials with high crystallinity through solution processing at low temperature. Herein, we demonstrated a high-brightness green light-emitting diode based on PEDOT:PSS/CH
3
NH
3
PbBr
3
/ZnO sandwich structures by a spin-coating method combined with a sputtering system. Under forward bias, a dominant emission peak at ∼530 nm with a low full width of half-maximum (FWHM) of 30 nm can be achieved at room temperature. Owing to the high surface coverage of the CH
3
NH
3
PbBr
3
layer and a device design based on carrier injection and a confinement configuration, the proposed diode exhibits good electroluminescence performance, with an external quantum efficiency of 0.0645%. More importantly, we investigated the working stability of the studied diode under continuous operation to verify the sensitivity of the electroluminescence performance to ambient atmosphere and to assess the suitability of the diode for practical applications. Moreover, the underlying reasons for the undesirable emission decay are tentatively discussed. This demonstration of an effective green electroluminescence based on CH
3
NH
3
PbBr
3
provides valuable information for the design and development of perovskites as efficient emitters, thus facilitating their use in existing applications and suggesting new potential applications.
We demonstrated a high-brightness green light-emitting diodes based on PEDOT:PSS/CH
3
NH
3
PbBr
3
/ZnO sandwiched structures.
Bloom syndrome protein (BLM) is a conserved RecQ family helicase involved in the maintenance of genome stability. BLM has been widely recognized as a genome “caretaker” that processes structured DNA. ...In contrast, our knowledge of how BLM behaves on single‐stranded (ss) DNA is still limited. Here, we demonstrate that BLM possesses the intrinsic ability for phase separation and can co‐phase separate with ssDNA to form dynamically arrested protein/ssDNA co‐condensates. The introduction of ATP potentiates the capability of BLM to condense on ssDNA, which further promotes the compression of ssDNA against a resistive force of up to 60 piconewtons. Moreover, BLM is also capable of condensing replication protein A (RPA)‐ or RAD51‐coated ssDNA, before which it generates naked ssDNA by dismantling these ssDNA‐binding proteins. Overall, our findings identify an unexpected characteristic of a DNA helicase and provide a new angle of protein/ssDNA co‐condensation for understanding the genomic instability caused by BLM overexpression under diseased conditions.
Single‐molecule optical‐tweezers analysis revealed that Bloom syndrome helicase can undergo phase separation and form condensates on single‐stranded (ss) DNA, giving rise to the compression and condensation of ssDNA into the condensates that are stable in the presence of a high resistant force.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To explore the sesquiterpenoids in
L. and their activity related to anti-atherosclerosis. The chemical compounds of the rhizomes of
were separated and purified by multiple chromatography techniques. ...Their structures were established by a variety of spectroscopic experiments. The absolute configurations were determined by comparing experimental and calculated NMR chemical shifts and electronic circular dichroism (ECD) spectra. Their anti-inflammatory effects and inhibitory activity against macrophage-derived foam cell formation were evaluated by lipopolysaccharide (LPS) and oxidized low-density lipoprotein (ox-LDL)-injured RAW264.7 macrophages, respectively. This study resulted in the isolation of 10 bisabolane-type sesquiterpenoids (
-
) from
, including two pairs of new epimers (curbisabolanones A-D,
-
). Compound
significantly inhibited LPS-induced nitric oxide (NO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) production in RAW264.7 cells. Furthermore, compound
showed inhibitory activity against macrophage-derived foam cell formation, which was represented by markedly reducing ox-LDL-induced intracellular lipid accumulation as well as total cholesterol (TC), free cholesterol (FC), and cholesterol ester (CE) contents in RAW264.7 cells. These findings suggest that bisabolane-type sesquiterpenoids, one of the main types of components in
, have the potential to alleviate the atherosclerosis process by preventing inflammation and inhibiting macrophage foaming.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Liver‐expressed antimicrobial peptide 2 (LEAP2) is a highly conserved secretory peptide first isolated in 2003. However, its exact biological functions remained elusive until a recent study ...identified it as an endogenous antagonist for the growth hormone secretagogue receptor (GHSR1a), a G protein‐coupled receptor for which the gastric peptide ghrelin is the endogenous agonist. By tuning the ghrelin–GHSR1a system, LEAP2 has an important function in energy metabolism. In the present study, we first demonstrated that LEAP2 and ghrelin actually bound to GHSR1a in a competitive manner, rather than in a non‐competitive manner as previously reported, by binding assays and activation assays. Subsequently, we demonstrated that the antagonistic function of LEAP2 was drastically affected by the manner of its addition. LEAP2 primarily affected the maximal activation effect when added before ghrelin, whereas it primarily affected half‐maximal effective concentration when added at the same time as ghrelin. Thus, LEAP2 behaved as a competitive antagonist if added at the same time as the agonist and a non‐competitive antagonist if added before the agonist. This unusual property of LEAP2 might be caused by its slow dissociation from receptor GHSR1a. We also found that the N‐terminal fragment of LEAP2 was important for receptor binding. Our present study revealed an antagonistic mechanism for LEAP2, and will facilitate the design of novel antagonists for receptor GHSR1a in future studies.
Using binding assays, we demonstrated liver‐expressed antimicrobial peptide 2 (LEAP2) was a competitive antagonist for ghrelin receptor GHSR1a. However, the manner of addition affected LEAP2's function in activation assays: it behaved as a competitive antagonist when added at the same time as ghrelin, whereas it behaved as a non‐competitive antagonist when added before ghrelin. Its slow dissociation from GHSR1a might cause this unusual property. This study provides new insights into LEAP2's tuning of the ghrelin–GHSR1a system.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Protein products of the regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, ...the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA-DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.
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