A susceptible person experiences the highest exposure risk of respiratory infection when he or she is in close proximity with an infected person. The large droplet route has been commonly believed to ...be dominant for most respiratory infections since the early 20th century, and the associated droplet precaution is widely known and practiced in hospitals and in the community. The mechanism of exposure to droplets expired at close contact, however, remains surprisingly unexplored. In this study, the exposure to exhaled droplets during close contact (<2 m) via both the short-range airborne and large droplet sub-routes is studied using a simple mathematical model of expired flows and droplet dispersion/deposition/inhalation, which enables the calculation of exposure due to both deposition and inhalation. The short-range airborne route is found to dominate at most distances studied during both talking and coughing. The large droplet route only dominates when the droplets are larger than 100 μm and when the subjects are within 0.2 m while talking or 0.5 m while coughing. The smaller the exhaled droplets, the more important the short-range airborne route. The large droplet route contributes less than 10% of exposure when the droplets are smaller than 50 μm and when the subjects are more than 0.3 m apart, even while coughing.
•The smaller the exhaled droplets, the more important the short-range airborne route.•Exhalation velocity impacts significantly on droplet travel distance and size change.•The large droplet route only dominates when the subjects are within 0.2 m while talking or 0.5 m while coughing.•The large droplet route contributes less than 10% of exposure when the droplets are smaller than 50 μm at 0.3 m apart.
Pulmonary fibrosis (PF) is a senescence‐associated disease with poor prognosis. Currently, there is no effective therapeutic strategy for preventing and treating the disease process. Mounting ...evidence suggests that arachidonic acid (ARA) metabolites are involved in the pathogenesis of various fibrosis. However, the relationship between the metabolism of ARA and PF is still elusive. In this study, we observed a disorder in the cyclooxygenase‐2/cytochrome P450 (COX‐2/CYP) metabolism of ARA in the lungs of PF mice induced by bleomycin (BLM). Therefore, we aimed to explore the role of COX‐2/CYP‐derived ARA metabolic disorders in PF. PTUPB, a dual COX‐2 and soluble epoxide hydrolase (sEH) inhibitor, was used to restore the balance of COX‐2/CYP metabolism. sEH is an enzyme hydrolyzing epoxyeicosatrienoic acids derived from ARA by CYP. We found that PTUPB alleviated the pathological changes in lung tissue and collagen deposition, as well as reduced senescence marker molecules (p16Ink4a and p53‐p21Waf1/Cip1) in the lungs of mice treated by BLM. In vitro, we found that PTUPB pretreatment remarkably reduced the expression of senescence‐related molecules in the alveolar epithelial cells (AECs) induced by BLM. In conclusion, our study supports the notion that the COX‐2/CYP‐derived ARA metabolic disorders may be a potential therapeutic target for PF via inhibiting the cellular senescence in AECs.
Here, we observed a disorder in the cyclooxygenase‐2/cytochrome P450 (COX‐2/CYP) metabolism of arachidonic acid in the lungs of mice with pulmonary fibrosis (PF) induced by bleomycin. PTUPB, a dual COX‐2 and soluble epoxide hydrolase inhibitor, was used to restore the balance of COX‐2/CYP metabolism. Our findings showed that PTUPB alleviated bleomycin‐induced PF via inhibiting the cellular senescence in alveolar epithelial cells, indicating a potential therapeutic target for PF.
From the perspective of disease prevention, the enhancement of cognitive function among the healthy older people has become an important issue in many countries lately. This study aim to investigate ...the effect of cognitive-based training on the overall cognitive function, memory, attention, executive function, and visual-spatial ability of the healthy older people.
Cochrane, PubMed, EMBASE, MEDLINE, PsycINFO, and CINAHL of selected randomized controlled trials (RCTs), and previous systematic reviews were searched for eligible studies. The population focused on this study were healthy older people who participated in randomized controlled trials that investigated the effectiveness of cognitive-based training. The outcomes including change in overall cognitive function, memory, attention, executive function, and visual-spatial ability.
We collected a total of 31 RCTs, the results showed that cognitive-based training has a moderate effect on overall cognitive function (g = 0.419; 95%CI = 0.205-0.634) and executive function (g = 0.420; 95%CI = 0.239-0.602), and a small effect on the memory (g = 0.354; 95%CI = 0.244-0.465), attention (g = 0.218; 95%CI = 0.125-0.311), and visual-spatial ability (g = 0.183;95%CI = 0.015-0.352) in healthy older people. Subgroup analysis indicated the intervention characteristics of ≧3 times each week (p = 0.042), ≧8 total training weeks (p = 0.003) and ≧24 total training sessions (p = 0.040) yields a greater effect size.
Cognitive-based training is effective for the healthy older people. This improvement can represent a clinically important benefit, provide information about the use of cognitive-based training in healthy older people, and help the healthy older people obtain the greatest possible benefit in health promotion and disease prevention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Jaundice is a common symptom of inherited or acquired liver diseases or a manifestation of diseases involving red blood cell metabolism. Recent progress has elucidated the molecular mechanisms of ...bile metabolism, hepatocellular transport, bile ductular development, intestinal bile salt reabsorption, and the regulation of bile acids homeostasis.
The major genetic diseases causing jaundice involve disturbances of bile flow. The insufficiency of bile salts in the intestines leads to fat malabsorption and fat-soluble vitamin deficiencies. Accumulation of excessive bile acids and aberrant metabolites results in hepatocellular injury and biliary cirrhosis. Progressive familial intrahepatic cholestasis (PFIC) is the prototype of genetic liver diseases manifesting jaundice in early childhood, progressive liver fibrosis/cirrhosis, and failure to thrive. The first three types of PFICs identified (PFIC1, PFIC2, and PFIC3) represent defects in FIC1 (ATP8B1), BSEP (ABCB11), or MDR3 (ABCB4). In the last 5 years, new genetic disorders, such as TJP2, FXR, and MYO5B defects, have been demonstrated to cause a similar PFIC phenotype. Inborn errors of bile acid metabolism also cause progressive cholestatic liver injuries. Prompt differential diagnosis is important because oral primary bile acid replacement may effectively reverse liver failure and restore liver functions. DCDC2 is a newly identified genetic disorder causing neonatal sclerosing cholangitis. Other cholestatic genetic disorders may have extra-hepatic manifestations, such as developmental disorders causing ductal plate malformation (Alagille syndrome, polycystic liver/kidney diseases), mitochondrial hepatopathy, and endocrine or chromosomal disorders. The diagnosis of genetic liver diseases has evolved from direct sequencing of a single gene to panel-based next generation sequencing. Whole exome sequencing and whole genome sequencing have been actively investigated in research and clinical studies. Current treatment modalities include medical treatment (ursodeoxycholic acid, cholic acid or chenodeoxycholic acid), surgery (partial biliary diversion and liver transplantation), symptomatic treatment for pruritus, and nutritional therapy. New drug development based on gene-specific treatments, such as apical sodium-dependent bile acid transporter (ASBT) inhibitor, for BSEP defects are underway.
Understanding the complex pathways of jaundice and cholestasis not only enhance insights into liver pathophysiology but also elucidate many causes of genetic liver diseases and promote the development of novel treatments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
Plants form complex interaction networks with diverse microbiomes in the environment, and the intricate interplay between plants and their associated microbiomes can greatly influence ...ecosystem processes and functions. The phyllosphere, the aerial part of the plant, provides a unique habitat for diverse microbes, and in return the phyllosphere microbiome greatly affects plant performance. As an open system, the phyllosphere is subjected to environmental perturbations, including global change, which will impact the crosstalk between plants and their microbiomes. In this review, we aim to provide a synthesis of current knowledge of the complex interactions between plants and the phyllosphere microbiome under global changes and to identify future priority areas of research on this topic.
Cancer stem cells (CSCs) are considered responsible for the recurrence and chemoresistance of cancer. Dysregulated autophagy is highly prevalent in many types of cancer including pancreatic cancer ...and has been implicated in cytoprotection and tumor promotion. This study aimed to investigate the role of autophagy in regulating cancer stemness and chemoresistance of pancreatic cancer.
The correlation between autophagy and CSCs and its clinical significance were analyzed using pancreatic cancer tissue microarrays. Genetic and pharmacological approaches were applied to explore the function of autophagy on CSC activity and gemcitabine resistance of pancreatic cancer cells in vitro and in vivo.
LC3 expression positively correlated with the expression of CSC markers aldehyde dehydrogenase 1 (ALDH1), CD44, and CD133 in pancreatic cancer tissues. High coexpression of LC3/ALDH1 was associated with both poor overall survival and progression-free survival. In pancreatic cancer cell lines, higher LC3-II expression was observed in the sphere-forming cells than in the bulk cells. Blockade of autophagy by silencing ATG5, ATG7, and BECN1 or the administration of autophagy inhibitor chloroquine markedly reduced the CSC populations, ALDH1 activity, sphere formation, and resistance to gemcitabine in vitro and in vivo. Furthermore, osteopontin (OPN) was found to stimulate LC3-II, ALDH1, CD44, and CD133 expression in PANC-1 cells, whereas this effect could be prevented by OPN knockdown and autophagy blockade. After treatment with various inhibitors against the major signaling pathways downstream of OPN, only the inhibitor of NF-κB activation, BAY 1170-82, could effectively counteract OPN-induced autophagy and CSC activity. According to the histochemical results, pancreatic cancer patients manifesting high levels of OPN/LC3/ALDH1 and OPN/CD44/CD133 had poor survival.
Induction of autophagy mediated by OPN/NF-κB signaling is required for maintenance of pancreatic CSC activity. Combination of gemcitabine with pharmacological autophagy inhibitors is a promising therapeutic strategy for pancreatic cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This work aims to provide a reliable and intelligent prediction model for future trends in sharing economy. Moreover, it presents valuable insights for decision-making and policy development by ...relevant governmental bodies. Furthermore, the study introduces a predictive system that incorporates an enhanced Harris Hawk Optimization (HHO) algorithm and a K-Nearest Neighbor (KNN) forecasting framework. The method utilizes an improved simulated annealing mechanism and a Gaussian bare bone structure to improve the original HHO, termed SGHHO. To achieve optimal prediction performance and identify essential features, a refined simulated annealing mechanism is employed to mitigate the susceptibility of the original HHO algorithm to local optima. The algorithm employs a mechanism that boosts its global search ability by generating fresh solution sets at a specific likelihood. This mechanism dynamically adjusts the equilibrium between the exploration and exploitation phases, incorporating the Gaussian bare bone strategy. The best classification model (SGHHO-KNN) is developed to mine the key features with the improvement of both strategies. To assess the exceptional efficacy of the SGHHO algorithm, this investigation conducted a series of comparative trials employing the function set of IEEE CEC 2014. The outcomes of these experiments unequivocally demonstrate that the SGHHO algorithm outperforms the original HHO algorithm on 96.7% of the functions, substantiating its remarkable superiority. The algorithm can achieve the optimal value of the function on 67% of the tested functions and significantly outperforms other competing algorithms. In addition, the key features selected by the SGHHO-KNN model in the prediction experiment, including " Form of sharing economy in your region " and " Attitudes to the sharing economy ", are important for predicting the future trends of the sharing economy in this study. The results of the prediction demonstrate that the proposed model achieves an accuracy rate of 99.70% and a specificity rate of 99.38%. Consequently, the SGHHO-KNN model holds great potential as a reliable tool for forecasting the forthcoming trajectory of the sharing economy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Necroptosis, a recently described form of programmed cell death, is the main way of alveolar epithelial cells (AECs) death in acute lung injury (ALI). While the mechanism of how to trigger ...necroptosis in AECs during ALI has been rarely evaluated. Long optic atrophy protein 1 (L‐OPA1) is a crucial mitochondrial inner membrane fusion protein, and its deficiency impairs mitochondrial function. This study aimed to investigate the role of L‐OPA1 deficiency‐mediated mitochondrial dysfunction in AECs necroptosis. We comprehensively investigated the detailed contribution and molecular mechanism of L‐OPA1 deficiency in AECs necroptosis by inhibiting or activating L‐OPA1. First, our data showed that L‐OPA1 expression was downregulated in the lungs and AECs under the lipopolysaccharide (LPS) challenge. Furthermore, inhibition of L‐OPA1 aggravated the pathological injury, inflammatory response, and necroptosis in the lungs of LPS‐induced ALI mice. In vitro, inhibition of L‐OPA1 induced necroptosis of AECs, while activation of L‐OPA1 alleviated necroptosis of AECs under the LPS challenge. Mechanistically, inhibition of L‐OPA1 aggravated necroptosis of AECs by inducing mitochondrial fragmentation and reducing mitochondrial membrane potential. While activation of L‐OPA1 had the opposite effects. In summary, these findings indicate for the first time that L‐OPA1 deficiency mediates mitochondrial fragmentation, induces necroptosis of AECs, and exacerbates ALI in mice.
L‐OPA1 deficiency mediates mitochondrial fragmentation, induces necroptosis of alveolar epithelial cells, and exacerbates acute lung injury in mice.
Diverse plant-associated fungi are thought to have symbiotrophic and saprotrophic states because they can be isolated from both dead and living plant tissues. However, such tissues often are ...separated in time and space, and fungal activity at various stages of plant senescence is rarely assessed directly in fungal community studies.
We used fungal ribosomal RNA metatranscriptomics to detect active fungal communities across a natural senescence gradient within wild-collected gametophytes of Dicranum scoparium (Bryophyta) to understand the distribution of active fungal communities in adjacent living, senescing and dead tissues.
Ascomycota were active in all tissues across the senescence gradient. By contrast, Basidiomycota were prevalent and active in senescing and dead tissues. Several fungi were detected as active in living and dead tissues, suggesting their capacity for multi-trophy. Differences in community assembly detected by metatranscriptomics were echoed by amplicon sequencing of cDNA and compared to culture-based inferences and observation of fungal fruit bodies in the field.
The combination of amplicon sequencing of cDNA and metatranscriptomics is promising for studying symbiotic systems with complex microbial diversity, allowing for the simultaneous detection of their presence and activity.
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