A hybrid water quality prediction model based on variational mode decomposition and bidirectional gated recursive unit.

Water quality predicted accuracy is beneficial to river ecological management and water pollution prevention. Owing to water quality data has the characteristics of nonlinearity and instability, it is difficult to predict the change of water quality. This paper proposes a hybrid water quality prediction model based on variational mode decomposition optimized by the sparrow search algorithm (SSA-VMD) and bidirectional gated recursive unit (BiGRU). First, the sparrow search algorithm selects fuzzy entropy (FE) as the fitness function to optimize the two parameters of VMD, which improves the adaptability of VMD. Second, SSA-VMD is used to decompose the original data into several components with different center frequencies. Finally, BiGRU is employed to predict each component separately, which significantly improves predicted accuracy. The proposed model is validated using data about dissolved oxygen (DO) and the potential of hydrogen (pH) from the Xiaojinshan Monitoring Station in Qiandao Lake, Hangzhou, China. The experimental results show that the proposed model has superior prediction accuracy and stability when compared with other models, such as EMD-based models and other CEEMDAN-based models. The prediction accuracy of DO can reach 97.8% and pH is 96.1%. Therefore, the proposed model can provide technical support for river water quality protection and pollution prevention.

Quantifying changes in oxygen saturation of the internal jugular vein in vivo using deep neural networks and subject-specific three-dimensional Monte Carlo models.

Central venous oxygen saturation (ScvO2) is an important parameter for assessing global oxygen usage and guiding clinical interventions. However, measuring ScvO2 requires invasive catheterization. As an alternative, we aim to noninvasively and continuously measure changes in oxygen saturation of the internal jugular vein (SijvO2) by a multi-channel near-infrared spectroscopy system. The relation between the measured reflectance and changes in SijvO2 is modeled by Monte Carlo simulations and used to build a prediction model using deep neural networks (DNNs). The prediction model is tested with simulated data to show robustness to individual variations in tissue optical properties. The proposed technique is promising to provide a noninvasive tool for monitoring the stability of brain oxygenation in broad patient populations.

Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner.

Fusobacterium nucleatum, a gram-negative oral bacterium, has been consistently validated as a strong contributor to the progression of several types of cancer, including colorectal (CRC) and pancreatic cancer. While previous in vitro studies have shown that intracellular F. nucleatum enhances malignant phenotypes such as cell migration, the dependence of this regulation on features of the tumor microenvironment (TME) such as oxygen levels are wholly uncharacterized. Here we examine the influence of hypoxia in facilitating F. nucleatum invasion and its effects on host responses focusing on changes in the global epigenome and transcriptome. Using a multiomic approach, we analyze epigenomic alterations of H3K27ac and global transcriptomic alterations sustained within a hypoxia and normoxia conditioned CRC cell line HCT116 at 24 h following initial infection with F. nucleatum. Our findings reveal that intracellular F. nucleatum activates signaling pathways and biological processes in host cells similar to those induced upon hypoxia conditioning in the absence of infection. Furthermore, we show that a hypoxic TME favors F. nucleatum invasion and persistence and therefore infection under hypoxia may amplify malignant transformation by exacerbating the effects induced by hypoxia alone. These results motivate future studies to investigate host-microbe interactions in tumor tissue relevant conditions that more accurately define parameters for targeted cancer therapies.

Optimizing the lyophilization of Lumbricus terrestris erythrocruorin.

Haemorrhagic shock is a leading cause of death worldwide. Blood transfusions can be used to treat patients suffering severe blood loss but donated red blood cells (RBCs) have several limitations that limit their availability and use. To solve the problems associated with donated RBCs, several acellular haemoglobin-based oxygen carriers (HBOCs) have been developed to restore the most important function of blood: oxygen transport. One promising HBOC is the naturally extracellular haemoglobin (i.e. erythrocruorin) of Lumbricus terrestris (LtEc). The goal of this study was to maximise the portability of LtEc by lyophilising it and then testing its stability at elevated temperatures. To prevent oxidation, several cryoprotectants were screened to determine the optimum formulation for lyophilisation that could minimise oxidation of the haem iron and maximise recovery. Furthermore, samples were also deoxygenated prior to storage to decrease auto-oxidation, while resuspension in a solution containing ascorbic acid was shown to partially reduce LtEc that had oxidised during storage (e.g. from 42% Fe3+ to 11% Fe3+). Analysis of the oxygen equilibria and size of the resuspended LtEc showed that the lyophilisation, storage, and resuspension processes did not affect the oxygen transport properties or the structure of the LtEc, even after 6 months of storage at 40 °C. Altogether, these efforts have yielded a shelf-stable LtEc powder that can be stored for long periods at high temperatures, but future animal studies will be necessary to prove that the resuspended product is a safe and effective oxygen transporter in vivo.

Physiologic Determinants of Near-Infrared Spectroscopy-Derived Cerebral and Tissue Oxygen Saturation Measurements in Critically Ill Patients.

OBJECTIVES: Near-infrared spectroscopy (NIRS) is a potentially valuable modality to monitor the adequacy of oxygen delivery to the brain and other tissues in critically ill patients, but little is known about the physiologic determinants of NIRS-derived tissue oxygen saturations. The purpose of this study was to assess the contribution of routinely measured physiologic parameters to tissue oxygen saturation measured by NIRS. DESIGN: An observational sub-study of patients enrolled in the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomized feasibility trial. SETTING: Two ICUs in the United Kingdom. PATIENTS: Patients were recruited for the RADAR-2 study, which compared a conservative approach to fluid therapy and deresuscitation with usual care. Those included in this sub-study underwent continuous NIRS monitoring of cerebral oxygen saturations (SctO2) and quadriceps muscle tissue saturations (SmtO2). INTERVENTION: Synchronized and continuous mean arterial pressure (MAP), heart rate (HR), and pulse oximetry (oxygen saturation, Spo2) measurements were recorded alongside NIRS data. Arterial Paco2, Pao2, and hemoglobin concentration were recorded 12 hourly. Linear mixed effect models were used to investigate the association between these physiologic variables and cerebral and muscle tissue oxygen saturations. MEASUREMENTS AND MAIN RESULTS: Sixty-six patients were included in the analysis. Linear mixed models demonstrated that Paco2, Spo2, MAP, and HR were weakly associated with SctO2 but only explained 7.1% of the total variation. Spo2 and MAP were associated with SmtO2, but together only explained 0.8% of its total variation. The remaining variability was predominantly accounted for by between-subject differences. CONCLUSIONS: Our findings demonstrated that only a small proportion of variability in NIRS-derived cerebral and tissue oximetry measurements could be explained by routinely measured physiologic variables. We conclude that for NIRS to be a useful monitoring modality in critical care, considerable further research is required to understand physiologic determinants and prognostic significance.

Fungal diversity in sediments of the eastern tropical Pacific oxygen minimum zone revealed by metabarcoding.

Oxygen minimum zones (OMZ) represent ~8% of the ocean, with the Pacific as the largest and top expanding area. These regions influence marine ecosystems, promoting anaerobic microbial communities. Nevertheless, only a fraction of microbial diversity has been studied, with fungi being the less explored component. So, herein we analyzed fungal diversity patterns in surface and subsurface sediments along a bathymetric transect using metabarcoding of the ITS1 region in the OMZ of the Mexican Pacific off Mazatlán. We identified 353 amplicon sequence variants (ASV), within the Ascomycota, Basidiomycota, and Rozellomycota. Spatial patterns evidenced higher alpha diversity in nearshore and subsurface subsamples, probably due to temporal fluctuations in organic matter inputs. Small-scale heterogeneity characterized the community with the majority of ASV (269 ASV) occurring in a single subsample, hinting at the influence of local biogeochemical conditions. This baseline data evidenced a remarkable fungal diversity presenting high variation along a bathymetric and vertical transects.

[Evaluation of the photodynamic effect on the state of microcirculation and oxygenation in periodontal tissues in the treatment of chronic generalized periodontitis]. / Otsenka fotodinamicheskogo vozdeistviya na sostoyanie mikrotsirkulyatsii i oksigenatsii v tkanyakh parodonta pri lechenii khronicheskogo generalizovannogo parodontita.

OBJECTIVE: Increasing the effectiveness of treatment of chronic generalized periodontitis using PDT based on clinical and functional substantiation of the effects of a photosensitizer. MATERIALS AND METHODS: A clinical and functional study and treatment of moderate chronic generalized periodontitis was carried out in 62 people (26 men and 36 women) aged from 35 to 55 years without a somatic model with an orthognathic occlusion diagnosed according to ICD-10 - K05.3. Of these, 2 groups were divided depending on the type of treatment: Group 1 (main) - patients with moderate chronic generalized periodontitis - 32 people. (17 men and 15 women, average age of the group - 43.2±2.2 years); Group 2 (control) - patients with moderate chronic generalized periodontitis - 30 people. (14 men and 16 women, average age of the group - 44.0±3.3 years). Complex treatment consisted of sanitation of the mouth, removal of dental plaque and curettage of periodontal pockets in group 1, followed by PDT with Revixan gel using a special wired aligner REVIXAN DENTAL LED (16 r). The clinical condition of the periodontium was assessed using the Greene Vermillion Hygienic Index (OHI-S), the Mühlleman Bleeding Index (SBI) modified by Cowell, and the periodontal index PI. To study the state of microcirculation in the gum tissue, the laser Doppler flowmetry (LDF) method was used using the LAKK-M device (NPP «Lazma¼, Russia). The state of microcirculation was assessed by the microcirculation index (M), which characterizes the level of tissue blood flow; parameter - «σ¼, which determines the fluctuation of the erythrocyte flow. According to Wavelet analysis of LDF-grams, the shunt index (SH) of blood flow was determined. In the «LDF + spectrometry¼ mode, oxygenation in periodontal tissues was studied using optical tissue oximetry (OTO), based on the results of which the perfusion saturation index (Sm) and the specific oxygen consumption index (U, %) were determined. RESULTS: According to LDF data, after PDT (group 1), normalization of clinical indices and the level of microcirculation in periodontal tissues was established, which was accompanied by an increase in the level of blood flow (M) and its activity (σ), which persisted after 3 and 6 months. after PDT. The perfusion saturation index (Sm) and specific oxygen consumption (U) increased more significantly after PDT, which persisted after 3 and 6 months. In the control group, the dynamics of indicators was less pronounced. CONCLUSION: The use of PDT with Revixan gel normalizes the clinical condition of the periodontium, indicators of microhemodynamics and oxygen metabolism.

Reservoir Computing Based on Oxygen-Vacancy-Mediated X-ray Optical Synaptic Device for Medical CT Bone Diagnosis.

Recognition and judgment of X-ray computed tomography (CT) images play a crucial role in medical diagnosis and disease prevention. However, the storage and calculation of the X-ray imaging system applied in the traditional CT diagnosis is separate, and the pathological judgment is based on doctors' experience, which will affect the timeliness and accuracy of decision-making. In this paper, a simple-structured reservoir computing network (RC) is proposed based on Ga2O3 X-ray optical synaptic devices to recognize medical skeletal CT images with high accuracy. Through oxygen vacancy engineering, Ga2O3 X-ray optical synaptic devices with adjustable photocurrent gain and a persistent photoconductivity effect were obtained. By using the Ga2O3 X-ray optical synaptic device as a reservoir, we constructed an RC network for medical skeletal CT diagnosis and verified its image recognition capability using the MNIST data set with an accuracy of 78.08%. In the elbow skeletal CT image recognition task, the recognition rate is as high as 100%. This work constructs a simple-structured RC network for X-ray image recognition, which is of great significance in applications in medical fields.

Impact of One-Lung Ventilation on Oxygenation and Ventilation Time in Thoracoscopic Heart Surgery: A Comparative Analysis with Median Thoracotomy.

BACKGROUND One-lung ventilation is the separation of the lungs by mechanical methods to allow ventilation of only one lung, particularly when there is pathology in the other lung. This retrospective study from a single center aimed to compare 49 patients undergoing thoracoscopic cardiac surgery using one-lung ventilation with 48 patients undergoing thoracoscopic cardiac surgery with median thoracotomy. MATERIAL AND METHODS This single-center retrospective study analyzed patients who underwent thoracoscopic cardiac surgery based on one-lung ventilation (experimental group, n=49). Other patients undergoing a median thoracotomy cardiac operation were defined as the comparison group (n=48). The oxygenation index and the mechanical ventilation time were also recorded. RESULTS There was no significant difference in the immediate oxygenation index between the experimental group and comparison group (P>0.05). There was no significant difference for the oxygenation index between men and women in both groups (P>0.05). The cardiopulmonary bypass time significantly affected the oxygenation index (F=7.200, P=0.009). Operation methods (one-lung ventilation thoracoscopy or median thoracotomy) affected postoperative ventilator use time (F=8.337, P=0.005). Cardiopulmonary bypass time (F=16.002, P<0.001) and age (F=4.384, P=0.039) had significant effects on ventilator use time. There was no significant effect of sex (F=0.75, P=0.389) on ventilator use time. CONCLUSIONS Our results indicated that one-lung ventilation thoracoscopic cardiac surgery did not affect the immediate postoperative oxygenation index; however, cardiopulmonary bypass time did significantly affect the immediate postoperative oxygenation index. Also, one-lung ventilation thoracoscopic cardiac surgery had a shorter postoperative mechanical ventilation use time than did traditional median thoracotomy cardiac surgery.

Absorbing oxygen carriers promotes phosphorus recovery from sludge via the microwave thermal conversion process.

This study aims to apply the Absorbing oxygen carriers (AOCs) to induce the migration and transformation of phosphorus compounds during the microwave thermal conversion of sludge so the hard-to-extract organic phosphorus (OP) can be converted to easy-to-extract inorganic phosphorus (IP) and be enriched onto the sludge char. The AOCs were recycled by screen separation from the IP-rich sludge char, with the latter being a renewable phosphorus source from sludge. The AOCs in this novel process enhanced the conversion efficiency of OP into non-apatite inorganic phosphorus (NAlP), which was further converted to apatite inorganic phosphorus (AP). Most phosphorus in the sludge char is presented in the form of orthophosphate.

3D intrusions transport active surface microbial assemblages to the dark ocean.

Subtropical oceans contribute significantly to global primary production, but the fate of the picophytoplankton that dominate in these low-nutrient regions is poorly understood. Working in the subtropical Mediterranean, we demonstrate that subduction of water at ocean fronts generates 3D intrusions with uncharacteristically high carbon, chlorophyll, and oxygen that extend below the sunlit photic zone into the dark ocean. These contain fresh picophytoplankton assemblages that resemble the photic-zone regions where the water originated. Intrusions propagate depth-dependent seasonal variations in microbial assemblages into the ocean interior. Strikingly, the intrusions included dominant biomass contributions from nonphotosynthetic bacteria and enrichment of enigmatic heterotrophic bacterial lineages. Thus, the intrusions not only deliver material that differs in composition and nutritional character from sinking detrital particles, but also drive shifts in bacterial community composition, organic matter processing, and interactions between surface and deep communities. Modeling efforts paired with global observations demonstrate that subduction can flux similar magnitudes of particulate organic carbon as sinking export, but is not accounted for in current export estimates and carbon cycle models. Intrusions formed by subduction are a particularly important mechanism for enhancing connectivity between surface and upper mesopelagic ecosystems in stratified subtropical ocean environments that are expanding due to the warming climate.

Enhanced catalytic activity of Fe3O4-carbon dots complex in the Fenton reaction for enhanced immunotherapeutic and oxygenation effects.

Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3O4-carbon dots complex (Fe3O4-CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3O4-CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe3O4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe3O4-CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe3O4-CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1α) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe3O4-CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1α was investigated by immunofluorescence method. In vivo, Fe3O4-CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe3O4-CDs@Fc is a promising immune-antitumor drug.

25-hydroxycholesterol aggravates oxygen-glucose deprivation/reoxygenation-induced pyroptosis through promoting activation of NLRP3 inflammasome in H9C2 cardiomyocytes.

25-hydroxycholesterol (25-HC) plays a role in the regulation of cell survival and immunity. However, the effect of 25-HC on myocardial ischemia/reperfusion (MI/R) injury remains unknown. Our present study aimed to investigate whether 25-HC aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. The overlapping differentially expressed genes (DEGs) in MI/R were identified from the GSE775, GSE45818, GSE58486, and GSE46395 datasets in Gene Expression Omnibus (GEO) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the database of Annotation, Visualization and Integration Discovery (DAVID). The protein-protein interaction (PPI) network of the overlapping DEGs was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database. These bioinformatics analyses indicated that cholesterol 25-hydroxylase (CH25H) was one of the crucial genes in MI/R injury. The oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was established to simulate MI/R injury. Western blot and RT-qPCR analysis demonstrated that CH25H was significantly upregulated in OGD/R-stimulated H9C2 cardiomyocytes. Moreover, knockdown of CH25H inhibited the OGD/R-induced pyroptosis and nod-like receptor protein 3 (NLRP3) inflammasome activation, as demonstrated by cell counting kit-8 (CCK8), lactate dehydrogenase (LDH), RT-qPCR, and western blotting assays. Conversely, 25-HC, which is synthesized by CH25H, promoted activation of NLRP3 inflammasome in OGD/R-stimulated H9C2 cardiomyocytes. In addition, the NLRP3 inhibitor BAY11-7082 attenuated 25-HC-induced H9C2 cell injury and pyroptosis under OGD/R condition. In conclusion, 25-HC could aggravate OGD/R-induced pyroptosis through promoting activation of NLRP3 inflammasome in H9C2 cells.

The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration.

Understanding the molecular underpinnings of neurodegeneration processes is a pressing challenge for medicine and neurobiology. Alzheimer's disease (AD) and Parkinson's disease (PD) represent the most prevalent forms of neurodegeneration. To date, a substantial body of experimental evidence has strongly implicated hypoxia in the pathogenesis of numerous neurological disorders, including AD, PD, and other age-related neurodegenerative conditions. Hypoxia-inducible factor (HIF) is a transcription factor that triggers a cell survival program in conditions of oxygen deprivation. The involvement of HIF-1α in neurodegenerative processes presents a complex and sometimes contradictory picture. This review aims to elucidate the current understanding of the interplay between hypoxia and the development of AD and PD, assess the involvement of HIF-1 in their pathogenesis, and summarize promising therapeutic approaches centered on modulating the activity of the HIF-1 complex.

The Robust Lamina Cribrosa Vasculature: Perfusion and Oxygenation Under Elevated Intraocular Pressure.

Purpose: Elevated intraocular pressure (IOP) is thought to cause lamina cribrosa (LC) blood vessel distortions and potentially collapse, adversely affecting LC hemodynamics, reducing oxygenation, and triggering, or contributing to, glaucomatous neuropathy. We assessed the robustness of LC perfusion and oxygenation to vessel collapses. Methods: From histology, we reconstructed three-dimensional eye-specific LC vessel networks of two healthy monkey eyes. We used numerical simulations to estimate LC perfusion and from this the oxygenation. We then evaluated the effects of collapsing a fraction of LC vessels (0%-36%). The collapsed vessels were selected through three scenarios: stochastic (collapse randomly), systematic (collapse strictly by the magnitude of local experimentally determined IOP-induced compression), and mixed (a combination of stochastic and systematic). Results: LC blood flow decreased linearly as vessels collapsed-faster for stochastic and mixed scenarios and slower for the systematic one. LC regions suffering severe hypoxia (oxygen <8 mm Hg) increased proportionally to the collapsed vessels in the systematic scenario. For the stochastic and mixed scenarios, severe hypoxia did not occur until 15% of vessels collapsed. Some LC regions had higher perfusion and oxygenation as vessels collapsed elsewhere. Some severely hypoxic regions maintained normal blood flow. Results were equivalent for both networks and patterns of experimental IOP-induced compression. Conclusions: LC blood flow was sensitive to distributed vessel collapses (stochastic and mixed) and moderately vulnerable to clustered collapses (systematic). Conversely, LC oxygenation was robust to distributed vessel collapses and sensitive to clustered collapses. Locally normal flow does not imply adequate oxygenation. The actual nature of IOP-induced vessel collapse remains unknown.

Experimental study of organic enrichment on meiofaunal diversity.

The organic enrichment effects on the meiofauna and nematofauna were assessed for field sediment and other experimental ones enriched with organic matters conducted in the laboratory for 4 weeks. Also, dissolved oxygen (DO) and pH were monitored for each one. The abundance and diversity of meiofaunal groups and nematofauna varied. Strong significant correlations were found between DO and the studied items. Nematoda was the most abundant group in the field sediment and other experimental ones; their counts increased with the increase in organic enrichments and were dominated by deposit feeders. Amphipoda, Ostracoda and predator/omnivore nematodes disappeared in highly organic-enriched sediments. Changes in DO and organic enrichments might be the more attributable reasons for the alteration of the meiobenthic assemblages. The generic compositions of Nematoda provide a good indicator for environmental alterations.

Functional availability of medical oxygen for the management of hypoxaemia in Cameroon: A nationwide facility-based cross-sectional survey.

Background: Medical oxygen is essential for managing hypoxaemia, which has a multifactorial origin, including acute and chronic lung diseases such as pneumonia, asthma, and severe malaria. The coronavirus disease 2019 (COVID-19) revealed substantial gaps in the availability and accessibility of safe medical oxygen, especially in low- and middle-income countries (LMICs). This study aimed to assess the availability and sources, as well as the barriers to the availability of functional medical oxygen in hospitals in Cameroon. Methods: This was a nationwide cross-sectional descriptive study conducted from 26 March to 1 June 2021. Using a convenient sampling technique, we sampled accredited public and private COVID-19 treatment centres in all ten regions in Cameroon. Representatives from the selected hospitals were provided with a pre-designed questionnaire assessing the availability, type, and state of medical oxygen in their facilities. All analyses were performed using R. Results: In total, 114 hospitals were included in this study, with functional medical oxygen available in 65% (74/114) of the hospitals. About 85% (23/27) of the reference hospitals and only 59% (51/87) of the district hospitals had available functional medical oxygen. Compared to district hospitals, reference hospitals were more likely to have central oxygen units (reference vs. district: 10 vs. 0%), oxygen cylinders (74 vs. 42%), and oxygen concentrators (79 vs. 51%). The most common barriers to the availability of medical oxygen were inadequate oxygen supply to meet needs (district vs. reference hospitals: 55 vs. 30%), long delays in oxygen bottle refills (51 vs. 49%), and long distances from oxygen suppliers (57 vs. 49%). Conclusions: The availability of medical oxygen in hospitals in Cameroon is suboptimal and more limited in districts compared to reference hospitals. The cost of medical oxygen, delays related to refills and supplies, and long distances from medical sources were the most common barriers to availability in Cameroon.

Molecular and physiological characterization of AIP1, encoding the acetolactate synthase regulatory subunit in rice.

Flooding deprives plants of oxygen and thereby causes severe stress by interfering with energy production, leading to growth retardation. Enzymes and metabolites may help protect plants from waterlogging and hypoxic environmental conditions. Acetolactate synthase (ALS) is a key enzyme in the biosynthesis of branched-chain amino acids (BCAAs), providing the building blocks for proteins and various secondary metabolites. Additionally, under energy-poor conditions, free BCAAs can be used as an alternative energy source by mitochondria through a catabolic enzyme chain reaction. In this study, we characterized ALS-INTERACTING PROTEIN 1 (OsAIP1), which encodes the regulatory subunit of ALS in rice (Oryza sativa). This gene was expressed in all parts of the rice plant, and its expression level was significantly higher in submerged and low-oxygen environments. Rice transformants overexpressing OsAIP1 showed a higher survival rate under hypoxic stress than did non-transgenic control plants under the same conditions. The OsAIP1-overexpressing plants accumulated increased levels of BCAAs, demonstrating that OsAIP1 is an important factor in the hypoxia resistance mechanism. These results suggest that ALS proteins are part of a defense mechanism that improves the tolerance of plants to low-oxygen environments.

In silico model development and optimization of in vitro lung cell population growth.

Tissue engineering predominantly relies on trial and error in vitro and ex vivo experiments to develop protocols and bioreactors to generate functional tissues. As an alternative, in silico methods have the potential to significantly reduce the timelines and costs of experimental programs for tissue engineering. In this paper, we propose a methodology to formulate, select, calibrate, and test mathematical models to predict cell population growth as a function of the biochemical environment and to design optimal experimental protocols for model inference of in silico model parameters. We systematically combine methods from the experimental design, mathematical statistics, and optimization literature to develop unique and explainable mathematical models for cell population dynamics. The proposed methodology is applied to the development of this first published model for a population of the airway-relevant bronchio-alveolar epithelial (BEAS-2B) cell line as a function of the concentration of metabolic-related biochemical substrates. The resulting model is a system of ordinary differential equations that predict the temporal dynamics of BEAS-2B cell populations as a function of the initial seeded cell population and the glucose, oxygen, and lactate concentrations in the growth media, using seven parameters rigorously inferred from optimally designed in vitro experiments.

AngioMT: A MATLAB based 2D image-to-physics tool to predict oxygen transport in vascularized microphysiological systems.

Microphysiological models (MPS) are increasingly getting recognized as in vitro preclinical systems of pathophysiology and drug discovery. However, there is also a growing need to adapt and advance MPS to include the physiological contributions of the capillary vascular dynamics, because they undergo angiogenesis or vasculogenesis to deliver soluble oxygen and nutrients to its organs. Currently, the process of formation of microvessels in MPS is measured arbitrarily, and vascularized MPS do not include oxygen measurements in their analysis. Sensing and measuring tissue oxygen delivery is extremely difficult because it requires access to opaque and deep tissue, and/or requires extensive integration of biosensors that makes such systems impractical to use in the real world. Here, a finite element method-based oxygen transport program, called AngioMT, is built in MATLAB. AngioMT processes the routinely acquired 2D confocal images of microvascular networks in vitro and solves physical equations of diffusion-reaction dominated oxygen transport phenomena. This user-friendly image-to-physics transition in AngioMT is an enabling tool of MPS analysis because unlike the averaged morphological measures of vessels, it provides information of the spatial transport of oxygen both within the microvessels and the surrounding tissue regions. Further, it solves the more complex higher order reaction mechanisms which also improve the physiological relevance of this tool when compared directly against in vivo measurements. Finally, the program is applied in a multicellular vascularized MPS by including the ability to define additional organ/tissue subtypes in complex co-cultured systems. Therefore, AngioMT serves as an analytical tool to enhance the predictive power and performance of MPS that incorporate microcirculation.