A large number of studies have explored the association between frailty and mortality among COVID-19 patients, with inconsistent results. The aim of this meta-analysis was to synthesize the evidence ...on this issue.
Three databases, PubMed, Embase, and Cochrane Library, from inception to 20th January 2021 were searched for relevant literature. The Newcastle-Ottawa Scale (NOS) was used to assess quality bias, and STATA was employed to pool the effect size by a random effects model. Additionally, potential publication bias and sensitivity analyses were performed.
Fifteen studies were included, with a total of 23,944 COVID-19 patients, for quantitative analysis. Overall, the pooled prevalence of frailty was 51% (95% CI: 44-59%). Patients with frailty who were infected with COVID-19 had an increased risk of mortality compared to those without frailty, and the pooled hazard ratio (HR) and odds ratio (OR) were 1.99 (95% CI: 1.66-2.38) and 2.48 (95% CI: 1.78-3.46), respectively. In addition, subgroup analysis based on population showed that the pooled ORs for hospitalized patients in eight studies and nursing home residents in two studies were 2.62 (95% CI: 1.68-4.07) and 2.09 (95% CI: 1.40-3.11), respectively. Subgroup analysis using the frailty assessment tool indicated that this association still existed when using the clinical frailty scale (CFS) (assessed in 6 studies, pooled OR = 2.88, 95% CI: 1.52-5.45; assessed in 5 studies, pooled HR = 1.99, 95% CI: 1.66-2.38) and other frailty tools (assessed in 4 studies, pooled OR = 1.98, 95% CI: 1.81-2.16). In addition, these significant positive associations still existed in the subgroup analysis based on study design and geographic region.
Our study indicates that frailty is an independent predictor of mortality among patients with COVID-19. Thus, frailty could be a prognostic factor for clinicians to stratify high-risk groups and remind doctors and nurses to perform early screening and corresponding interventions urgently needed to reduce mortality rates in patients infected by SARS-CoV-2.
Highly enantioselective 3+3 and 3+4 annulations of isatin‐derived enals with ethynylethylene carbonates and ethynyl benzoxazinanones are enabled by NHC/cooper cooperative catalysis, leading to a big ...library of spirooxindole derivatives in high structural diversity and enantioselectivity (up to 99 % ee). Both reactions represent a nicely synergistic integration of NHC and copper catalysis, in which both catalysts activate the substrates and the chiral NHC perfectly controls the stereochemistry.
All together now: A cooperative N‐heterocyclic carbene (NHC)/cooper catalytic system was developed for the diversity‐oriented synthesis of spirooxindole derivatives through enantioselective 3+3 and 3+4 annulation reactions. Highly enantioselective 3+3 and 3+4 annulations of isatin‐derived enals with ethynylethylene carbonates and ethynyl benzoxazinanones were achieved.
Neurodegenerative diseases generally result in irreversible neuronal damage and neuronal death. Cell therapy shows promise as a potential treatment for these diseases. However, the therapeutic ...targeted delivery of these cells and the in situ provision of a suitable microenvironment for their differentiation into functional neuronal networks remain challenging. A highly integrated multifunctional soft helical microswimmer featuring targeted neuronal cell delivery, on‐demand localized wireless neuronal electrostimulation, and post‐delivery enzymatic degradation is introduced. The helical soft body of the microswimmer is fabricated by two‐photon lithography of the photocurable gelatin–methacryloyl (GelMA)‐based hydrogel. The helical body is then impregnated with composite multiferroic nanoparticles displaying magnetoelectric features (MENPs). While the soft GelMA hydrogel chassis supports the cell growth, and is degraded by enzymes secreted by cells, the MENPs allow for the magnetic transportation of the bioactive chassis, and act as magnetically mediated electrostimulators of neuron‐like cells. The unique combination of the materials makes these microswimmers highly integrated devices that fulfill several requirements for their future translation to clinical applications, such as cargo delivery, cell stimulation, and biodegradability. The authors envision that these devices will inspire new avenues for targeted cell therapies for traumatic injuries and diseases in the central nervous system.
Biodegradable soft magnetoelectric microswimmers are fabricated using a 3D‐printing technique. These microswimmers can perform targeted delivery of neuron‐like cells and induce neuronal differentiation of these cells under different magnetic stimulation modes. This combinatorial technique is a significant step towards highly integrated microrobots, and may open up new avenues for cell therapies.
Mobile micro‐ and nanorobots are proposed for future biomedical applications, such as diagnostics and targeted delivery. For their translation to clinical practice, biocompatibility and ...biodegradability of micro‐ and nanorobots are required aspects. The fabrication of small‐scale robots with non‐cytotoxic biodegradable soft components will allow for enhanced device assimilation, optimal tissue interaction and minimized immune reactions. The 3D microfabrication of biodegradable soft helical microswimmers via two‐photon polymerization of the non‐toxic photocrosslinkable hydrogel gelatin methacryloyl (GelMA) is reported. GelMA microswimmers are fabricated with user‐defined geometry and rendered magnetically responsive by decorating their surface with magnetic nanoparticles. In contrast to previous rigid helical microrobots, the soft helical microswimmers can corkscrew above the step‐out frequency with relatively high values of forward velocity, suggesting an unprecedented self‐adaptive behavior. Cytotoxicity assays show the toxicity of GelMA is at least three orders of magnitude lower than that of poly(ethyleneglycol) diacrylates, which are widely used for fabricating hydrogel‐based microswimmers. GelMA microswimmers are fully degradable by collagenases. Furthermore, they support cell attachment and growth, and are gradually digested by cell‐released enzymes during culture. These non‐cytotoxic biodegradable hydrogel microswimmers will greatly expand their applications in medicine by eliminating the concerns of retrieving microrobots after fulfilling tasks in body.
Biodegradable soft helical microswimmers are successfully developed based on two‐photon photopolymerization of a gelatin derivative, GelMA. By decorating their surface with magnetic nanoparticles, these microswimmers can be manipulated by magnetic field. Because of the proteolytic cleavage of peptide domains in gelatin, microswimmers made of GelMA can be fully degraded by cell‐secreted proteases.
Background and Aim
Remimazolam tosilate (RT) is a new short‐acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy ...and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy.
Methods
This positive‐controlled, non‐inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety.
Results
The success rate of sedation in the RT group was non‐inferior to that in the propofol group (97.34% vs 100.00%; difference in rate −2.66%, 95% CI −4.96 to −0.36, meeting criteria for non‐inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment‐related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001).
Conclusion
This trial established non‐inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.
Sodium‐ion batteries (SIBs) are still confronted with several major challenges, including low energy and power densities, short‐term cycle life, and poor low‐temperature performance, which severely ...hinder their practical applications. Here, a high‐voltage cathode composed of Na3V2(PO4)2O2F nano‐tetraprisms (NVPF‐NTP) is proposed to enhance the energy density of SIBs. The prepared NVPF‐NTP exhibits two high working plateaux at about 4.01 and 3.60 V versus the Na+/Na with a specific capacity of 127.8 mA h g−1. The energy density of NVPF‐NTP reaches up to 486 W h kg−1, which is higher than the majority of other cathode materials previously reported for SIBs. Moreover, due to the low strain (≈2.56% volumetric variation) and superior Na transport kinetics in Na intercalation/extraction processes, as demonstrated by in situ X‐ray diffraction, galvanostatic intermittent titration technique, and cyclic voltammetry at varied scan rates, the NVPF‐NTP shows long‐term cycle life, superior low‐temperature performance, and outstanding high‐rate capabilities. The comparison of Ragone plots further discloses that NVPF‐NTP presents the best power performance among the state‐of‐the‐art cathode materials for SIBs. More importantly, when coupled with an Sb‐based anode, the fabricated sodium‐ion full‐cells also exhibit excellent rate and cycling performances, thus providing a preview of their practical application.
A high‐voltage sodium‐super‐ion‐conductor‐type cathode significantly enhances the energy density of sodium‐ion batteries. Its low‐strain crystal lattice during the successive (de‐)sodiation and superior Na transport kinetics promise high‐rate capabilities, long‐term cycle life, superior low‐temperature performance, and excellent full‐cell performance, providing a preview of their practical applications.
Grafting of C7 from the nonparalyzed to the paralyzed side in patients with arm paralysis resulted in greater improvements in power, spasticity, and function at 12 months than rehabilitation therapy ...alone, and functional connection to the ipsilateral cerebral hemisphere developed.
Kcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains ...unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE
mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE
mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway.
The strategy of inducing interlayer anionic ligands in 2D MoS1.5Se0.5 nanosheets is employed to consolidate the interlayer band gap and optimize the electronic structure for the potassium ion ...battery. It combines complementary advantages from two kinds of anionic ligands with high conductivity and good affinity with potassium ions. The potassium ion diffusion rate is accelerated as well by an optimized lower energy barrier for ion diffusion pathways, with the formation of highly reversible KMo3Se3 crystal other than K0.4MoS2/K2MoS4, which encounters a much slower electro/ion diffusion rate upon discharging. These advances deliver enhanced potassium storage properties with excellent cycling stability, with retained specific capacity of 531.6 mAh g−1 at a current density of 200 mA g−1 even after 1000 cycles, and high rate capability with specific capacity of 270.1 mAh g−1 at 5 A g−1. The insertion and conversion mechanism are also elucidated by a combination of density functional theory computations and in situ synchrotron measurements.
The strategy of inducing interlayer anionic ligands in 2D MoS1.5Se0.5 nanosheets is employed to consolidate the interlayer band gap and optimize the electronic structure for the potassium ion battery. It combines complementary advantages from two kinds of anionic ligands with high conductivity and good affinity with potassium ions.
Summary
WRKY transcription factors play important roles in response to various abiotic stresses. Previous study have proved that soybean GmWRKY54 can improve stress tolerance in transgenic ...Arabidopsis. Here, we generated soybean transgenic plants and further investigated roles and biological mechanisms of GmWRKY54 in response to drought stress. We demonstrated that expression of GmWRKY54, driven by either a constitutive promoter (pCm) or a drought‐induced promoter (RD29a), confers drought tolerance. GmWRKY54 is a transcriptional activator and affects a large number of stress‐related genes as revealed by RNA sequencing. Gene ontology (GO) enrichment and co‐expression network analysis, together with measurement of physiological parameters, supported the idea that GmWRKY54 enhances stomatal closure to reduce water loss, and therefore confers drought tolerance in soybean. GmWRKY54 directly binds to the promoter regions of genes including PYL8, SRK2A, CIPK11 and CPK3 and activates them. Therefore GmWRKY54 achieves its function through abscisic acid (ABA) and Ca2+ signaling pathways. It is valuable that GmWRKY54 activates an ABA receptor and an SnRK2 kinase in the upstream position, unlike other WRKY proteins that regulate downstream genes in the ABA pathway. Our study revealed the role of GmWRKY54 in drought tolerance and further manipulation of this gene should improve growth and production in soybean and other legumes/crops under unfavorable conditions.
Significance Statement
This paper reveals that GmWRKY54 is a transcription factor that effectively modulates drought signaling, GmWRKY54 affects expression of large numbers of downstream genes that possess positive roles in drought tolerance. Using a precise analysis strategy of gene enrichment and co‐expression, it was discovered that GmWRKY54 confers drought tolerance through participating in the ABA and Ca2+ signaling pathways.
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