Sandwich-cultured hepatocytes (SCH) are metabolically competent and have proper localization of basolateral and canalicular transporters with functional bile networks. Therefore, this cellular model ...is a unique tool that can be used to estimate biliary excretion of compounds. SCH have been used widely to assess hepatobiliary disposition of endogenous and exogenous compounds and metabolites. Mechanistic modeling based on SCH data enables estimation of metabolic and transporter-mediated clearances, which can be used to construct physiologically based pharmacokinetic models for prediction of drug disposition and drug-drug interactions in humans. In addition to pharmacokinetic studies, SCH also have been used to study cytotoxicity and perturbation of biological processes by drugs and hepatically generated metabolites. Human SCH can provide mechanistic insights underlying clinical drug-induced liver injury (DILI). In addition, data generated in SCH can be integrated into systems pharmacology models to predict potential DILI in humans. In this review, applications of SCH in studying hepatobiliary drug disposition and bile acid-mediated DILI are discussed. An example is presented to show how data generated in the SCH model were used to establish a quantitative relationship between intracellular bile acids and cytotoxicity, and how this information was incorporated into a systems pharmacology model for DILI prediction.
The molecular mechanisms regulating fate divergence of closely related, but distinct, layer 6 corticothalamic and layer 5 subcerebral projection neurons are largely unknown. We present evidence for ...central transcriptional mechanisms that regulate fate specification of corticothalamic (layer 6) and subcerebral (layer 5) projection neurons. We found that TBR1 promotes the identity of corticothalamic neurons and represses subcerebral fates through reducing expression of Fezf2 and CTIP2. These conclusions are based on the following: (1) In Tbr1(-/-) mice, the number of cells expressing layer 6 markers was reduced, and the number of cells expressing layer 5 markers was increased. Early-born (birthdated on E11.5) neurons ectopically expressed subcerebral neuronal markers, and extended their axons into subcerebral targets. (2) Ectopic Tbr1 expression in layer 5 neurons prevented them from extending axons into the brainstem and the spinal cord. (3) Chromatin immunoprecipitation analysis using TBR1 antibodies showed that TBR1 bound to a conserved region in the Fezf2 gene. (4) Analysis of Fezf2 mutants and Tbr1(-/-); Fezf2(-/-) compound mutants provided evidence that Fezf2 blocks corticothalamic fate in layer 5 by reducing Tbr1 expression in subcerebral neurons. All neocortical regions appear to use this core transcriptional program to specify corticothalamic (layer 6) and subcerebral (layer 5) projection neurons.
Four premolars extractions are routine procedures for correction of malocclusion, but will inevitably lead to a reduction of tongue space, whether this will weaken the pharyngeal airway remains a ...controversy.
Cone-beam computed tomography (CBCT) radiographs of 80 patients who completed four premolar extraction orthodontic treatments were collected and divided into three anteroposterior skeletal groups according to the ANB (angle subspinale to nasion to supramentale) value. Linear, angular, cross-sectional area, and volumetric dimensions of the pharyngeal airway were measured using Dolphin Imaging 11.9 software. One-way analysis of variance and Pearson's correlation coefficient test were performed to assess the intergroup comparisons. Treatment changes were evaluated with two-sample t-tests.
In intergroup comparisons, vertical linear and cross-sectional area differences were identified in S-Go/N-Me, VD1, VD1/N-Me, VD2/N-Me, AA, OAA and OMINI (p<0.05), while other measurements showed no significant differences. Angle2, the tilting degree of the pharyngeal airway, showed a positive correlation with ANB (p<0.05). As for the treatment changes, a significant increase was found in the pharyngeal airway in the Class I group (OUA p<0.05, VD1 p<0.001, VD2 p<0.05) and Class II group (VD1 p<0.001. VD2, p<0.05), and inversely, a significant decrease was found in the pharyngeal airway in the Class III group (OAA p<0.05, OMINI p<0.05, OUA p<0.05). No volumetric difference was identified. Interestingly, regarding the preoperative pharyngeal airway size, values trended to the mean value significantly.
Four premolar extraction orthodontic treatments did not affect the pharyngeal airway volume except for the vertical liner and cross-sectional area dimensions. The trend of the gold standard suggested a positive influence of four premolar extraction orthodontic treatments.
The stress-aging method is proposed to improve the dimensional stability of Al-Cu-Mg (2024 aluminum) alloy. Both the reduction of residual stress and the acceleration of precipitates are investigated ...during the stress-aging process. It is observed that some S′ particles precipitate in the alloy during stress-aging. With the external stress increase to 100 MPa, the residual stress and thermal strain (ɛc) decrease, while the micro-yield strength increases significantly. This is attributed to that the dislocations are effectively pinned by the uniformly distributed precipitates and the stored elastic energy diminishes remarkably, which leads to a considerable improvement of the dimensional stability of 2024 aluminum alloy. However, when further increases the external stress to 150 MPa, due to the coarsened precipitates, the residual stress and thermal strain increase, while the micro-yield strength decreases slightly.
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•Stress-aging method is proposed to enhance the dimensional stability of AA2024.•The needle-shaped S′ precipitates disperse in aluminum matrix during aging process.•Pinning dislocation and eliminating elastic energy improve dimensional stability.•The optimal applied stress for stress-aging method is 100 MPa.
Classifying the diverse ways that plants respond to hydrologic stress into generalizable ‘water‐use strategies’ has long been an eco‐physiological research goal. While many schemes for describing ...water‐use strategies have proven to be quite useful, they are also associated with uncertainties regarding their theoretical basis and their connection to plant carbon and water relations. In this review, we discuss the factors that shape plant water stress responses and assess the approaches used to classify a plant's water‐use strategy, paying particular attention to the popular but controversial concept of a continuum from isohydry to anisohydry.
A generalizable and predictive framework for assessing plant water‐use strategies has been historically elusive, yet recent advances in plant physiology and hydraulics provide the field with a way past these obstacles. Specifically, we promote the idea that many metrics that quantify water‐use strategies are highly dynamic and emergent from the interaction between plant traits and environmental conditions, and that this complexity has historically hindered the development of a generalizable water‐use strategy framework.
This idea is explored using a plant hydraulics model to identify: (a) distinct temporal phases in plant hydraulic regulation during drought that underpin dynamic water‐use responses, and (b) how variation in both traits and environmental forcings can significantly alter common metrics used to characterize plant water‐use strategies. This modelling exercise can bridge the divide between various conceptualizations of water‐use strategies and provide targeted hypotheses to advance the understanding and quantification of plant water status regulation across spatial and temporal scales.
Finally, we describe research frontiers that are necessary to improve the predictive capacity of the plant water‐use strategy concept, including further investigation into the below‐ground determinants of plant water relations, targeted data collection efforts and the potential to scale these concepts from individuals to whole regions.
A free Plain Language Summary can be found within the Supporting Information of this article.
A free Plain Language Summary can be found within the Supporting Information of this article.
Contemporary tree growth shows altered climate memory Peltier, Drew M. P.; Anderegg, William R. L.; Guo, Jessica S. ...
Ecology letters,
December 2022, 2022-12-00, 20221201, Letnik:
25, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Trees are long‐lived organisms, exhibiting temporally complex growth arising from strong climatic “memory.” But conditions are becoming increasingly arid in the western USA. Using a century‐long ...tree‐ring network, we find altered climate memory across the entire range of a widespread western US conifer: growth is supported by precipitation falling further into the past (+15 months), while increasingly impacted by more recent temperature conditions (−8 months). Tree‐ring datasets can be biased, so we confirm altered climate memory in a second, ecologically‐sampled tree‐ring network. Predicted drought responses show trees may have also become more sensitive to repeat drought. Finally, plots near sites with relatively longer precipitation memory and shorter temperature memory had significantly lower recent mortality rates (R2 = 0.61). We argue that increased drought frequency has altered climate memory, demonstrate how non‐stationarity may arise from failure to account for memory, and suggest memory length may be predictive of future tree mortality.
Tree growth is driven by precipitation and temperature conditions years prior, a process referred to as “memory.” Over the past century, memory of precipitation in Pinon edulis has become longer and temperature memory shorter, probably due to enhanced drought stress. We show memory shifts may be associated with reduced recent mortality risk, and that models ignoring memory may be more likely to find apparent non‐stationarity.
Simultaneous observations from Defense Meteorological Satellite Program, Swarm, Resolute Bay all‐sky imagers, GPS Total Electron Content and Super Dual Auroral Radar Network, are used to investigate ...the evolution and key characteristics of the Tongue of Ionization (TOI) being restructured into a polar cap patch. Six satellites crossed the TOI of patch as it moved from the dayside to the nightside. It was initially hot, then a mix of both cold and hot, and finally it became a cold patch. This suggests that cold patch is not only a result of solar extreme ultraviolet radiation, but may also develop when a hot patch cools down. Soft‐electron precipitation and flow shears both contribute to the TOI restructuring and the appearance of polar cap patch. The plasma density of patch at ∼500 km was at least 4 times higher than at ∼800 km. The plasma density enhancement gradually decreased as the patch evolved due to decreased production and transport of cold nightside low‐density plasma. Moreover, the duskward motion of the patch was influenced by changes in the ionospheric convection pattern.
Plain Language Summary
The appearance of high‐density plasma is a common phenomenon in the polar ionosphere. High‐density polar cap patches usually form near the dayside sunlit region, and then move from the dayside to the nightside with the ionospheric flow. In the paper, we use multiple instruments including six satellites and ground‐based observations to carefully investigate an event that started out on the dayside. It was initially a hot tongue of ionization (TOI) of high density and high electron temperature, followed by a mix of hot and cold (high vs. low electron temperature), before it finally became a cold patch. Soft‐electron precipitation and flow shears both influenced the dayside high‐density TOI plasma restructuring and the appearance of polar cap patch. The enhanced plasma density gradually weakened as the plasma migrated toward the nightside due to decreased production and transport of cold nightside low‐density plasma. Moreover, the duskward motion of the patch was influenced by changes in the ionospheric convection pattern.
Key Points
Cold dense plasma in the polar cap can appear either via transport of solar extreme ultraviolet plasma or after a hot patch cools down
Soft‐electron precipitation and flow shears both influence the Tongue of Ionization restructuring and the appearance of polar cap patches
The enhanced plasma density is reduced due to decreased production and transport of cold nightside low‐density plasma
Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to 'functional' postoperative acute kidney injury (AKI), ...measured by an abrupt increase in serum creatinine. Whether the same is true for 'structural' AKI, measured with new urinary biomarkers, is unknown.
The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: 'none' (no exposure prior to surgery), 'held' (on chronic ACEi/ARB but held on the morning of surgery) or 'continued' (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were 'functional' AKI based upon changes in pre- to postoperative serum creatinine, and 'structural AKI', based upon peak postoperative levels of four urinary biomarkers of kidney injury.
Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein).
Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by coughing, the production of excess sputum, and dyspnea. Patients with excessively thick sputum may ...have frequent attacks or develop more serious disease. The guidelines recommend airway clearance for patients with excessive sputum who are hospitalized with COPD. The active cycle of breathing technique is the most common non-pharmacological airway clearance technique used by physiotherapists. However, the effectiveness of the technique is not always guaranteed. Active cycle of breathing techniques require the initial dilution of the sputum, usually by inhalation drugs, which may have limited effects. Recent studies have found that phonophoresis decreases inflammation, suggesting the potential of the combined usage of active cycle of breathing techniques and phonophoresis. Therefore, the aim of this study is to explore the effectiveness and safety of combining active cycle of breathing technique and phonophoresis in treating COPD patients.
We propose a single-blind randomized controlled trial using 75 hospitalized patients diagnosed with COPD with excessive sputum production. The patients will be divided into three groups. The intervention group will receive active cycle of breathing techniques combined with phonophoresis. The two comparison groups will be treated with active cycle of breathing techniques and phonophoresis, respectively. The program will be implemented daily for 1 week. The primary outcomes will be changes in sputum viscosity and production, lung function, and pulse oximetry. Secondary outcomes include the assessment of COPD and anxiety, measured by the COPD Assessment Test scale and the Anxiety Inventory for Respiratory Disease, respectively; self-satisfaction; the degree of cooperation; and the length of hospital stay. All outcome measures, with the exception of sputum production and additional secondary outcomes, will be assessed at the commencement of the study and after 1 week's intervention. Analysis of variance will be used to investigate differences between the groups, and a p-value of less than 0.05 (two-tailed) will be considered statistically significant.
This study introduces a combination of active cycle of breathing techniques and phonophoresis to explore the impact of these interventions on patients hospitalized with COPD. If this combined intervention is shown to be effective, it may prove to be a better treatment for patients with COPD.
The trial was registered prospectively on the Chinese Clinical Trial Registry on 24 December 2019.ClinicalTrials.gov ChiCTR1900028506 . Registered on December 2019.
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