Abstract
Background
Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This ...study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19.
Methods
This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.
Results
Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33),
p
< 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38),
p
< 0.001. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33),
p
< 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56),
p
< 0.001 and controls TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33),
p
< 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38),
p
< 0.001. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients dementia: 25 (10.50 %) vs. 9 (0.69 %),
p
< 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %),
p
< 0.001 and controls dementia: 25 (10.50 %) vs. 0 (0 %),
p
< 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %),
p
< 0.001). COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline.
Conclusions
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.
Two-dimensional materials provide extraordinary opportunities for exploring phenomena arising in atomically thin crystals. Beginning with the first isolation of graphene, mechanical exfoliation has ...been a key to provide high-quality two-dimensional materials, but despite improvements it is still limited in yield, lateral size and contamination. Here we introduce a contamination-free, one-step and universal Au-assisted mechanical exfoliation method and demonstrate its effectiveness by isolating 40 types of single-crystalline monolayers, including elemental two-dimensional crystals, metal-dichalcogenides, magnets and superconductors. Most of them are of millimeter-size and high-quality, as shown by transfer-free measurements of electron microscopy, photo spectroscopies and electrical transport. Large suspended two-dimensional crystals and heterojunctions were also prepared with high-yield. Enhanced adhesion between the crystals and the substrates enables such efficient exfoliation, for which we identify a gold-assisted exfoliation method that underpins a universal route for producing large-area monolayers and thus supports studies of fundamental properties and potential application of two-dimensional materials.
The role of solution aggregates on the charge transport process of conjugated polymers in electronic devices has gained increasing attention; however, the correlation of the charge carrier mobilities ...between the solution aggregates and the solid‐state films remains elusive. Herein, three polymers, FBDOPV‐2T, FBDOPV‐2F2T, and FBDOPV‐4F2T, are designed and synthesized with distinct aggregation behavior in solution. By combining contact‐free ultrafast terahertz (THz) spectroscopy and field‐effect transistor measurements, we track the charge carrier mobility of the aggregates of these polymers from the solution to the thin‐film state. Remarkably, the mobility of these three polymers is found to follow nearly the same trend (FBDOPV‐2T>FBDOPV‐2F2T≫FBDOPV‐4F2T) in both solutions and thin‐film states. The quantitative mobility correlation indicates that the charge transport properties of solution aggregates play a critical role in determining the thin‐film charge transport properties and final device performance. Our results highlight the importance of investigating and controlling solution aggregation structures towards efficient organic electronic devices.
Different aggregation structures of three BDOPV‐based polymers in solution were obtained via subtle adjustment of the molecular structures. By employing contact‐free ultrafast terahertz (THz) spectroscopy, we directly reveal that the correlation of the charge carrier mobilities between the solution aggregates and the solid‐state films remains highly consistent.
Intracellular tau accumulation forming neurofibrillary tangles is hallmark pathology of Alzheimer's disease (AD), but how tau accumulation induces synapse impairment is elusive. By overexpressing ...human full‐length wild‐type tau (termed hTau) to mimic tau abnormality as seen in the brain of sporadic AD patients, we find that hTau accumulation activates JAK2 to phosphorylate STAT1 (signal transducer and activator of transcription 1) at Tyr701 leading to STAT1 dimerization, nuclear translocation, and its activation. STAT1 activation suppresses expression of N‐methyl‐D‐aspartate receptors (NMDARs) through direct binding to the specific GAS element of GluN1, GluN2A, and GluN2B promoters, while knockdown of STAT1 by AAV‐Cre in STAT1flox/flox mice or expressing dominant negative Y701F‐STAT1 efficiently rescues hTau‐induced suppression of NMDAR expression with amelioration of synaptic functions and memory performance. These findings indicate that hTau accumulation impairs synaptic plasticity through JAK2/STAT1‐induced suppression of NMDAR expression, revealing a novel mechanism for hTau‐associated synapse and memory deficits.
Synopsis
Tau accumulation, one hallmark of Alzheimer's disease, induces synaptic impairment by activating JAK2/STAT1 signaling, which transcriptionally suppresses N‐methyl‐D‐aspartate receptors. Downregulation of STAT1 ameliorates synaptic function and memory performance in mice.
Accumulation of hTau triggers JAK2‐dependent STAT1 dimerization, activation and nuclear translocation.
STAT1 activation directly suppresses N‐methyl‐D‐aspartate receptor expression.
Downregulation of STAT1 rescues hTau‐induced N‐methyl‐D‐aspartate receptor suppression.
Tau accumulation, one hallmark of Alzheimer's disease, induces synaptic impairment by activating JAK2/STAT1 signaling, which transcriptionally suppresses N‐methyl‐D‐aspartate receptors. Downregulation of STAT1 ameliorates synaptic function and memory performance in mice.
Abstract
Background
The duration of humoral and T and B cell response after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear.
Methods
We performed a ...cross-sectional study to assess the virus-specific antibody and memory T and B cell responses in coronavirus disease 2019 (COVID-19) patients up to 343 days after infection. Neutralizing antibodies and antibodies against the receptor-binding domain, spike, and nucleoprotein of SARS-CoV-2 were measured. Virus-specific memory T and B cell responses were analyzed.
Results
We enrolled 59 patients with COVID-19, including 38 moderate, 16 mild, and 5 asymptomatic patients; 31 (52.5%) were men and 28 (47.5%) were women. The median age was 41 years (interquartile range, 30–55). The median day from symptom onset to enrollment was 317 days (range 257 to 343 days). We found that approximately 90% of patients still have detectable immunoglobulin (Ig)G antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~60% of patients had detectable IgG antibodies against receptor-binding domain and surrogate virus-neutralizing antibodies. The SARS-CoV-2-specific IgG+ memory B cell and interferon-γ-secreting T cell responses were detectable in more than 70% of patients.
Conclusions
Severe acute respiratory syndrome coronavirus 2-specific immune memory response persists in most patients approximately 1 year after infection, which provides a promising sign for prevention from reinfection and vaccination strategy.
SARS-CoV-2-specific antibody and memory T and B cell responses were detectable in most patients approximately 1 year after infection, indicating that durable immunity against secondary COVID-19 disease is possible in most individuals.
IMPORTANCE: Determining the long-term impact of COVID-19 on cognition is important to inform immediate steps in COVID-19 research and health policy. OBJECTIVE: To investigate the 1-year trajectory of ...cognitive changes in older COVID-19 survivors. DESIGN, SETTING, AND PARTICIPANTS: This cohort study recruited 3233 COVID-19 survivors 60 years and older who were discharged from 3 COVID-19–designated hospitals in Wuhan, China, from February 10 to April 10, 2020. Their uninfected spouses (N = 466) were recruited as a control population. Participants with preinfection cognitive impairment, a concomitant neurological disorder, or a family history of dementia were excluded, as well as those with severe cardiac, hepatic, or kidney disease or any kind of tumor. Follow-up monitoring cognitive functioning and decline took place at 6 and 12 months. A total of 1438 COVID-19 survivors and 438 control individuals were included in the final follow-up. COVID-19 was categorized as severe or nonsevere following the American Thoracic Society guidelines. MAIN OUTCOMES AND MEASURES: The main outcome was change in cognition 1 year after patient discharge. Cognitive changes during the first and second 6-month follow-up periods were assessed using the Informant Questionnaire on Cognitive Decline in the Elderly and the Telephone Interview of Cognitive Status-40, respectively. Based on the cognitive changes observed during the 2 periods, cognitive trajectories were classified into 4 categories: stable cognition, early-onset cognitive decline, late-onset cognitive decline, and progressive cognitive decline. Multinomial and conditional logistical regression models were used to identify factors associated with risk of cognitive decline. RESULTS: Among the 3233 COVID-19 survivors and 1317 uninfected spouses screened, 1438 participants who were treated for COVID-19 (691 male 48.05% and 747 female 51.95%; median IQR age, 69 66-74 years) and 438 uninfected control individuals (222 male 50.68% and 216 female 49.32%; median IQR age, 67 66-74 years) completed the 12-month follow-up. The incidence of cognitive impairment in survivors 12 months after discharge was 12.45%. Individuals with severe cases had lower Telephone Interview of Cognitive Status-40 scores than those with nonsevere cases and control individuals at 12 months (median IQR: severe, 22.50 16.00-28.00; nonsevere, 30.00 26.00-33.00; control, 31.00 26.00-33.00). Severe COVID-19 was associated with a higher risk of early-onset cognitive decline (odds ratio OR, 4.87; 95% CI, 3.30-7.20), late-onset cognitive decline (OR, 7.58; 95% CI, 3.58-16.03), and progressive cognitive decline (OR, 19.00; 95% CI, 9.14-39.51), while nonsevere COVID-19 was associated with a higher risk of early-onset cognitive decline (OR, 1.71; 95% CI, 1.30-2.27) when adjusting for age, sex, education level, body mass index, and comorbidities. CONCLUSIONS AND RELEVANCE: In this cohort study, COVID-19 survival was associated with an increase in risk of longitudinal cognitive decline, highlighting the importance of immediate measures to deal with this challenge.
Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. ...Here, we characterize GSA1, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops.
Serum samples from patients convalescing after SARS-CoV-2 infection and after vaccination with BBIBP-CorV or CoronaVac in China neutralized pseudoviruses expressing spike proteins from the B.1.1.7 ...variant at levels that were similar to those from the wild-type (Wuhan) isolate but lower than those from the B.1.351 variant.
Platinum on carbon (Pt/C) catalyst is commercially adopted in fuel cells but it undergoes formidable active‐site poisoning by carbon monoxide (CO). In particular, given the sluggish kinetics of ...hydrogen oxidation reaction (HOR) in anion‐exchange membrane fuel cell (AEMFC), the issues of Pt poisoning and slow rate would combine mutually, notably worsening the device performances. Here we overcome these challenges through incorporating cobalt (Co) into molybdenum‐nickel alloy (MoNi4), termed Co‐MoNi4, which not only shows superior HOR activity over the Pt/C catalyst in alkali, but more intriguingly exhibits excellent CO tolerance with only small activity decay after 10 000 cycles in the presence of 500 parts per million (ppm) CO. When feeding with CO (250 ppm)/H2, the AEMFC assembled by this catalyst yields a peak power density of 394 mW cm−2, far exceeding the Pt/C catalyst. Experimental and computational studies reveal that weakened CO chemisorption originates from the electron‐deficient Ni sites after Co incorporation that suppresses d→CO 2π* back‐donation.
Incorporating Co into MoNi4 nanocatalyst can suppress the d→CO 2π* back donation, leading to excellent CO tolerance. When feeding with CO (250 ppm)/H2, the fuel cell assembled by this catalyst yields a peak power density of 394 mW cm−2, exceeding that of 209 mW cm−2 for the Pt/C catalyst.
PDF
