Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) of the elderly population. ...Sirtuin 1 (SIRT1), as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, has been reported to participate in various aging-related signaling pathways and exert protective effect on many human diseases. SIRT1 functioned as an important role in the occurrence and progression of sarcopenia through regulating key pathways related to protein homeostasis, apoptosis, mitochondrial dysfunction, insulin resistance and autophagy in skeletal muscle, including SIRT1/Forkhead Box O (FoxO), AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor κB (NF-κB), SIRT1/p53, AMPK/SIRT1/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and SIRT1/live kinase B1 (LKB1)/AMPK pathways. However, the specific mechanisms of these processes have not been fully illuminated. Currently, several SIRT1-mediated interventions on sarcopenia have been preliminarily developed, such as SIRT1 activator polyphenolic compounds, exercising and calorie restriction. In this review, we summarized the predominant mechanisms of SIRT1 involved in sarcopenia and therapeutic modalities targeting the SIRT1 signaling pathways for the prevention and prognosis of sarcopenia.
The phylum Apicomplexa comprises a group of obligate intracellular parasites that alternate between intracellular replicating stages and actively motile extracellular forms that move through tissue. ...Parasite cytosolic Ca2+ signalling activates motility, but how this is switched off after invasion is complete to allow for replication to begin is not understood. Here, we show that the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A catalytic subunit 1 (PKAc1) of Toxoplasma is responsible for suppression of Ca2+ signalling upon host cell invasion. We demonstrate that PKAc1 is sequestered to the parasite periphery by dual acylation of PKA regulatory subunit 1 (PKAr1). Upon genetic depletion of PKAc1 we show that newly invaded parasites exit host cells shortly thereafter, in a perforin-like protein 1 (PLP-1)-dependent fashion. Furthermore, we demonstrate that loss of PKAc1 prevents rapid down-regulation of cytosolic Ca2+ levels shortly after invasion. We also provide evidence that loss of PKAc1 sensitises parasites to cyclic GMP (cGMP)-induced Ca2+ signalling, thus demonstrating a functional link between cAMP and these other signalling modalities. Together, this work provides a new paradigm in understanding how Toxoplasma and related apicomplexan parasites regulate infectivity.
Spontaneous pneumothorax has a high incidence and high rate of recurrence in patients with lymphangioleiomyomatosis (LAM). The risk factors for pneumothorax and the effects of sirolimus on ...pneumothorax in patients with LAM are unknown. In our study, multivariate logistic regression was applied to a cross-sectional cohort to investigate factors associated with pneumothorax in LAM patients. Kaplan-Meier analysis was applied in the historical prospective self-controlled study to determine whether sirolimus reduces the risk of pneumothorax recurrence in patients with LAM. Of the 399 patients registered with LAM-CHINA at our center between May 10, 2017 and August 31, 2020, 142 had a history of pneumothorax at registration. High CT grade and age at presentation less than or equai to 35 years were associated with a higher risk of pneumothorax in patients with LAM. Postmenopausal status was correlated with a lower risk of pneumothorax. In the historical prospective self-controlled study, the 5-year probability of pneumothorax recurrence was 80% lower in the sirolimus group than in the control group (hazard ratio for pneumothorax recurrence, 0.20; 95% CI, 0.14 to 0.30, P < 0.001 by log-rank test). Sirolimus reduced the risk of pneumothorax recurrence in LAM patients.
The possible effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on COVID-19 disease severity have generated considerable debate. We performed a ...single-center, retrospective analysis of hospitalized adult COVID-19 patients in Wuhan, China, who had definite clinical outcome (dead or discharged) by February 15, 2020. Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes. The medical records from 702 patients were screened. Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication, 40 patients were receiving ACEI/ARB as part of their regimen, and 61 patients were on anti-hypertensive medication other than ACEI/ARB. We observed no statistically significant differences in percentages of in-hospital mortality (28% vs. 34%, P=0.46), ICU admission (20% vs. 28%, P=0.37) or invasive mechanical ventilation (18% vs. 26%, P=0.31) between patients with or without ACEI/ARB treatment. Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes. Our findings confirm the lack of an association between chronic receipt of renin-angiotensin system antagonists and severe outcomes of COVID-19. Patients should continue previous anti-hypertensive therapy until further evidence is available.
Abstract
Background
Sporadic lymphangioleiomyomatosis (S-LAM) is a rare neoplasm with heterogeneous clinical features that is conventionally considered to be related to
TSC2
. This study serves to ...elucidate the mutation landscape and potential correlation between S-LAM genomic profiles and clinical phenotypes.
Methods
Genomic profiles of 22 S-LAM patients were obtained by sequencing genomic DNA and cell-free DNA from various specimens using an NGS (next-generation sequencing)-based tumor-driver gene panel. Detected mutations were summarized. Symptoms, serum vascular endothelial growth factor D (VEGF-D) values, pulmonary function, and six-minute walk distance (6MWD) were compared among groups with different
TSC2
status and genotypes to analyze genotype–phenotype correlations.
Results
67 Variants in 43 genes were detected, with a
TSC2
mutation detection rate of 68.2%. The
TSC2
detection rate was similar in specimens obtained either through transbronchial lung biopsy (TBLB) or surgical lung biopsy (70.0% vs. 69.2%,
p
> 0.05). A novel mutation in
VEZF1
(c.A659G) was detected in four participants and may represent a mild disease state.
TSC2
mutation was significantly related to a shorter 6MWD (
p
< 0.05), and a higher percentage of VEGF-D over 800 pg/mL (
p
< 0.05); stop-gain mutation was significantly related to a higher prevalence of pneumothorax.
Conclusions
Tumor-driver mutations in genes other than
TSC2
may have a role in S-LAM, and TBLB specimens are practical alternatives for genomic analysis.
TSC2
mutation detectability and types are related to the disease severity and phenotypes of S-LAM.
The unmanned farm control platform is of great significance in promoting the supervision of farm production with less manpower or autonomous operation of farm machinery and the construction of farm ...informatization. Addressing the existing control platform for farm location information acquisition is time-consuming, labor-intensive, and lacks the whole process control of multiple types of farm machinery. In this paper, we propose an Internet of Things (IoT) control scheme for intelligent farm machinery operation of unmanned farms and design the access standards for multiple types of farm machinery, as well as realize the remote control of intelligent farm machinery operation by constructing a remote control model. A high-precision map construction method is designed to improve the DeepLabV3+ algorithm to identify fields and roads. The control models of path planning, remote task, remote control, and safety system are built to achieve the remote control of intelligent agricultural machinery operation. The proposed technology is implemented in the platform integration and application tests are carried out. The error of the constructed high-precision map is less than 3 cm, the completeness rate of the automatic boundary extraction rate is 96.71%, and the correctness rate is 95.63%, which can be used to obtain the boundary instead of manual labeling or on-site point picking. The use of the platform for the simultaneous control of three farm machinery operations reduces the number of people in operation and production and reduces the professional requirements of the personnel, which will promote the management of the entire farm by one person or even by no one in the future.
This paper presents for the first time a heterogeneous vehicular model with multiple moving small cells and a moving receiver with unreliable backhaul. In this system, a macro-base station connects to ...multiple moving small cells via wireless backhaul links. A Bernoulli process is adopted to model the backhaul reliability. A selection combining protocol is used at the receiver side to maximize the received signal-tonoise ratio. We investigate the impact of the number of moving small cells, the position of the receiver and the backhaul reliability on the system performance over double- Rayleigh fading channels. Expressions for outage probability are derived.
The in-situ mitigation of methane (CH4) in landfill gas using landfill cover soil (LCS) is a cost-effective approach, but its efficiency needs to be enhanced. In this study, we incorporated an ...enriched methane-oxidizing bacteria (MOB) consortium into LCS and established four biochar-amended LCS groups with biochar produced at 300 °C (BC300), 400 °C (BC400), 500 °C (BC500), and 600 °C (BC600). The purpose was to evaluate the CH4 oxidation capacity of biochar-amended LCS after inoculation with MOB and to investigate how the physicochemical properties of biochar that are influenced by the pyrolysis temperature affect the performance and microbial activity of biochar-amended LCS. It was found that a 15% volume ratio (representing a mass ratio of 2.49%–2.78%) for biochar amendment in LCS enhanced CH4 removal efficiency, with the highest removal observed to be 46% for BC400-amended LCS compared to 30% for the original LCS. In addition, CH4 adsorption by the biochar was not observed, and a 15% mass ratio for biochar in the LCS had no or a negative impact. Besides improving the water-holding capacity and gas permeability of LCS, other possible advantages of biochar amendment in terms of CH4 oxidization include greater retention of nutrients, electron acceptors, and exchangeable cations, as well as introducing iron ions. It was also found that CH4 oxidation capacity and the methanotroph activity of biochar-amended LCS did not continue to increase with higher pyrolysis temperatures, even though higher micropore volumes and surface areas were obtained at higher pyrolysis temperatures. From this study, BC400 was identified as the optimal choice for the best performance in terms of enhancing both the CH4 oxidation capacity of the amended LCS and the growth of type II methanotroph Methylocystaceae, which can possibly be attributed to having the highest cation exchange capacity of the four biochars.
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•Enriched MOB was inoculated to biochar-amended landfill cover soil (LCS).•In-situ CH4 mitigation of biochar-amended LCS was increased up to 46%.•The cation exchange capacity of biochar peaks at a pyrolysis temperature of 400 °C.•Biochar produced at 400 °C promotes the growth of type II methanotroph most in LCS.
Methane (CH4) mitigation of biocovers or biofilters for landfills is influenced by the bed material and oxygen availability. The improvement of active aeration for the CH4 oxidation efficiency of ...biochar-amended landfill soil cover was investigated over a period of 101 days. There were column 1 as the control group, column 2 with biochar amending the soil cover, and column 3 with daily active aeration besides the same biochar amendment. All groups were inoculated with enriched methane oxidation bacteria (MOB). The average CH4 removal efficiency was up to 78.6%, 85.2% and 90.6% for column 1, 2, and 3, respectively. The depth profiles of CH4 oxidation efficiencies over the whole period also showed that the stimulation of CH4 oxidation by biochar amendment was apparent in the top 35 cm but became very faint after two months. This probably was due to the rapid depletion of nitrogen nutrition caused by enhanced methanotrophic activities. While through aeration, CH4 oxidation efficiency was further improved for column 3 than column 2. This enhancement also lasted for the whole period with a reduced decline of CH4 oxidation. Finally, the major MOB Methylocystis, commonly found in the three columns, were most abundant in the top 35 cm for column 3. A more balanced ratio of MOB and more homogeneous microbial community structures across different soil depths were also the results of active aeration.
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•Active aeration was operated for biochar-amended landfill soil cover (LSC).•Average CH4 removal efficiency was 90.6% for biochar-amended and aerated LSC.•Active aeration enhanced and prolonged the stimulation of biochar amendment.•Active aeration resulted in more abundant and balanced MOB in the top 35 cm.
Use of corticosteroids is common in the treatment of coronavirus disease 2019, but clinical effectiveness is controversial. We aimed to investigate the association of corticosteroids therapy with ...clinical outcomes of hospitalized COVID-19 patients.
In this single-centre, retrospective cohort study, adult patients with confirmed coronavirus disease 2019 and dead or discharged between 29 December 2019 and 15 February 2020 were studied; 1:1 propensity score matchings were performed between patients with or without corticosteroid treatment. A multivariable COX proportional hazards model was used to estimate the association between corticosteroid treatment and in-hospital mortality by taking corticosteroids as a time-varying covariate.
Among 646 patients, the in-hospital death rate was higher in 158 patients with corticosteroid administration (72/158, 45.6% vs. 56/488, 11.5%, p < 0.0001). After propensity score matching analysis, no significant differences were observed in in-hospital death between patients with and without corticosteroid treatment (47/124, 37.9% vs. 47/124, 37.9%, p 1.000). When patients received corticosteroids before they required nasal high-flow oxygen therapy or mechanical ventilation, the in-hospital death rate was lower than that in patients who were not administered corticosteroids (17/86, 19.8% vs. 26/86, 30.2%, log rank p 0.0102), whereas the time from admission to clinical improvement was longer (13 (IQR 10–17) days vs. 10 (IQR 8–13) days; p < 0.001). Using the Cox proportional hazards regression model accounting for time varying exposures in matched pairs, corticosteroid therapy was not associated with mortality difference (HR 0.98, 95% CI 0.93–1.03, p 0.4694).
Corticosteroids use in COVID-19 patients may not be associated with in-hospital mortality.
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