Aging is an inevitable process of life. Defined by progressive physiological and functional loss of tissues and organs, aging increases the risk of mortality for the organism. The aging process is ...affected by various factors, including genetic and epigenetic ones. Here, we review the chromatin-specific epigenetic changes that occur during normal (chronological) aging and in premature aging diseases. Taking advantage of the reversible nature of epigenetic modifications, we will also discuss possible lifespan expansion strategies through epigenetic modulation, which was considered irreversible until recently.
Metabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe ...metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD
, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD
biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). NAD
repletion restores NAD
metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD
repletion remarkably extends lifespan and delays accelerated aging, including stem cell dysfunction, in Caenorhabditis elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WS is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD
levels counteracts WS phenotypes.
Senescence phenotypes and mitochondrial dysfunction are implicated in aging and in premature aging diseases, including ataxia telangiectasia (A‐T). Loss of mitochondrial function can drive ...age‐related decline in the brain, but little is known about whether improving mitochondrial homeostasis alleviates senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence‐associated secretory phenotype (SASP) occur in A‐T patient fibroblasts, and in ATM‐deficient cells and mice. Senescence is mediated by stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD+ levels with nicotinamide riboside (NR) prevents senescence and SASP by promoting mitophagy in a PINK1‐dependent manner. NR treatment also prevents neurodegeneration, suppresses senescence and neuroinflammation, and improves motor function in Atm−/− mice. Our findings suggest a central role for mitochondrial dysfunction‐induced senescence in A‐T pathogenesis, and that enhancing mitophagy as a potential therapeutic intervention.
The underlying cause in most A‐T cases is complex, likely reflecting risks premature aging, multiple genetic factors, and non‐genetic (e.g., environmental, lifestyle/behavioral, and metabolic) factors. These factors can directly/indirectly cause mitophagy defects, leading to accumulation of damaged mitochondria, a major feature of ATM‐deficient animals and A‐T patients. Damaged mitochondria accumulate and release DNA into cytoplasm, which activates STING‐induced glial responses, senescence and SASP. Mitophagy induction by NR treatment maintains a healthy mitochondrial pool and prevents STING activation through efficient clearance of dysfunctional mitochondria and maintains a healthy brain.
Abstract
Background
Some coronavirus disease 2019 (COVID-19) survivors experience prolonged and varying symptoms, a condition termed post-acute COVID-19 syndrome (PACS). However, the prevalence of ...chronic pulmonary sequelae of PACS during long-term follow-up remains unclear. Several studies have examined this issue and reported heterogeneous results.
Methods
We conducted a systematic review and meta-analysis using a random-effects model to estimate the pooled prevalence of the pulmonary sequelae of COVID-19, as demonstrated by pulmonary function testing (PFT) and chest computed tomography (CT) performed at least 6 months after initial infection. PubMed, Embase, and Cochrane Library databases were searched from January 1, 2020 to December 31, 2021 to identify related studies. We investigated whether the prevalence of pulmonary sequelae decreased over time and attempted to identify the factors associated with their development by performing multiple subgroup and meta-regression analyses.
Results
Of the 18,062 studies identified, 30 met our eligibility criteria. Among these studies, 25 and 22 had follow-up PFT and chest CT data, respectively. The follow-up durations were approximately 6 and 12 months in 18 and 12 studies, respectively. Impaired diffusion capacity was the most common abnormality on PFT (pooled prevalence 35%, 95% confidence interval CI 30–41%) with a prevalence of 39% (95% CI 34–45%) and 31% (95% CI 21–40%) in the 6-month and 12-month follow-up studies, respectively (
P
= 0.115). Restrictive pulmonary dysfunction evident as reduced forced vital capacity was less frequent (pooled prevalence 8%, 95% CI 6–11%); however, its prevalence was lower in the 12-month follow-up studies than in the 6-month follow-up studies (5% 95% CI 3–7% vs. 13% 95% CI 8–19%,
P
= 0.006). On follow-up chest CT, the pooled prevalence of persistent ground-glass opacities and pulmonary fibrosis was 34% (95% CI 24–44%) and 32% (95% CI 23–40%), respectively, and the prevalence did not decrease over time. As every meta-analysis showed significant between-study heterogeneity, subgroup and meta-regression analyses were performed to identify potential effect modifiers; the severity of index infection was associated with the prevalence of impaired diffusion capacity and pulmonary fibrosis.
Conclusions
A substantial number of COVID-19 survivors displayed pulmonary sequelae as part of PACS. Except for restrictive pulmonary dysfunction, the prevalence of these sequelae did not decrease until 1 year after initial infection. Considering the association between the severity of acute COVID-19 and risk of pulmonary sequelae, patients who recover from severe COVID-19 require close respiratory follow-up.
Systematic review registration number
PROSPERO CRD42021234357
ABSTRACT
Adipose‐derived stem cells (ADSCs) have been shown to induce wound‐healing effects. Because inflammation near the wound area induces oxygen deficiency, it is interesting to elucidate the ...effect of hypoxia on the function of ADSCs. In this work, we asked: (1) does hypoxia alter the wound‐healing function of ADSCs? and (2) what are the major factors responsible for the alteration in the wound‐healing function? Effect of hypoxia on the proliferation of ADSCs was first examined that hypoxia (2% O2) enhanced the proliferation of ADSCs in either the presence of serum or in the absence of serum. The conditioned medium of ADSCs harvested under hypoxia (hypoCM) significantly promoted collagen synthesis and the migration of human dermal fibroblasts, compared with that in normoxia (norCM). In the animal studies, hypoCM significantly reduced the wound area compared with norCM. Furthermore, mRNA and protein measurements showed that hypoxia up‐regulated growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Inhibition of VEGF and bFGF using neutralizing antibodies reversed the migration of the wounded human dermal fibroblasts and the healing of wounds in animal experiment. Collectively, these results suggest that hypoxia increases the proliferation of ADSCs and enhances the wound‐healing function of ADSCs, at least partly, by up‐regulating the secretion of VEGF and bFGF.
•Thiol functionalization on cellulose nanofiber surface imparting ability to adsorb metal ions.•Adsorption occurring only on the surface with homogeneously distributed adsorption energy.•Kinetic ...studies revealing the role of surface thiol in metal ion adsorption mechanism.•Expandability of cellulose for biocompatible, nontoxic, and sustainable water purification membrane applications.
This work reports the fabrication of a thiol-functionalized cellulose nanofiber membrane that can effectively adsorb heavy metal ions. Thiol was incorporated onto the surface of cellulose nanofibers, which were fabricated by the deacetylation of electrospun cellulose acetate nanofibers and subsequent esterification of a thiol precursor molecule. Adsorption mechanism was investigated using adsorption isotherms. Adsorption capacity as a function of adsorbate concentration was described well with Langmuir isotherm, suggesting that metal ions form a surface monolayer with a homogenously distributed adsorption energy. Maximum adsorption capacities in the Langmuir isotherm for Cu(II), Cd(II), and Pb(II) ions were 49.0, 45.9, and 22.0 mg·g−1, respectively. The time-dependent adsorption capacities followed a pseudo-second-order kinetic model, suggesting that chemisorption of each doubly charged metal ion occurs with two thiol groups on the surface. These results highlight the significance of surface functionality on biocompatible, nontoxic, and sustainable cellulose materials to expand their potential and applicability towards water remediation applications.
The visceral analgesic efficacy of erector spinae plane block (ESPB) is still a matter of debate. This study attempted to investigate the visceral analgesic efficacy of ESPB in clinical setting. ...After randomized, we performed ultrasound-guided bilateral rectus sheath block (RSB), which was aimed to prevent postoperative somatic pain on all patients who underwent laparoscopic cholecystectomy (LC). Ultrasound-guided bilateral ESPB at T7 level was performed only to the intervention group to provide the visceral analgesic block. The intraoperative requirement for remifentanil (P = 0.021) and the cumulative fentanyl consumption at postoperative 24-hours was significantly lower in the ESPB group (206.5 ± 82.8 μg vs.283.7 ± 102.4 μg, respectively; P = 0.004) compared to non-ESPB group. The ESPB group consistently showed lower accumulated analgesic consumption compared with those in the non-ESPB group at all observed time-points (all P < 0.05) after 2 hours and the degree of the accumulated analgesic consumption reduction was greater (P = 0.04) during the 24-hour postoperative period. Pain severity was lower in the ESPB group at 6-hours postoperatively. The significantly reduced opioid consumption in ESPB group may imply that while preliminary and in need of confirmation, ESPB has potential visceral analgesic effect. Therefore, performing ESPB solely may be feasible in inducing both somatic and visceral analgesia.
Scalable and economical manufacturing of flexible transparent conducting films (TCF) is a key barrier to widespread adoption of low‐cost flexible electronics. Here, a simple, robust, and scalable ...method of flexible TCF formation using supersonic kinetic spraying is demonstrated. Silver nanowire (AgNW) suspensions are sprayed at supersonic speed to produce self‐sintered films of AgNWs on flexible substrates. These films display remarkably low sheet resistance, <10 Ω sq−1, combined with high transmittance, >90%. These electrically conducting, transparent, and flexible coatings can be deposited over a 100 cm2 area in ≈30 s. Theoretical analysis reveals the underlying physical mechanism behind self‐sintering, showing that self‐sintering is enabled by the high velocity of impact in supersonic spraying.
A schematic of supersonic spraying of a silver nanowire (AgNW) film is shown. AgNWs are shown in an optical microscope image. Superdeposited nanowires with a junction are highlighted as a scanning electron microscopy (SEM) image.
Stereoscopic cloud-top height (CTH) retrieval from two geostationary (GEO) satellites is usually realized through a visible (VIS) band with a high horizontal resolution. A stereoscopic-based CTH ...retrieval algorithm (prototype dual-GEO CTH algorithm) proposed in our previous study also adopts this approach. Although this approach can retrieve accurate stereoscopic CTHs, the heights of optically thin upper clouds overlying the lower clouds are challenging to retrieve because the parallax difference between two GEOs is determined by the lower clouds owing to the low reflectance from the upper clouds. To address this problem, this paper proposes an improved stereoscopic CTH retrieval algorithm, named the improved dual-GEO CTH algorithm, for Himawari-8 and FengYun (FY)-4A GEOs. The proposed algorithm employs an infrared (IR) band in addition to a VIS band. A seamless image cloning technique is adopted to blend the VIS and IR images, which are then used to retrieve the stereoscopic CTHs. The retrieved CTHs are compared with the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) and Cloud Profiling Radar (CPR) CTHs for three occasions involving upper clouds overlying lower clouds. Results show that the proposed algorithm outperforms the prototype dual-GEO CTH algorithm in the case of upper clouds overlying lower clouds. Notably, although the proposed algorithm is intended for Himawari-8 and FY-4A GEOs, it can be easily extended to any combination of two GEOs.
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