Organ Systems Research Articles

Acute pancreatitis as a manifestation of multisystem inflammatory syndrome among children (MIS-C): A rare case

A multisystem inflammatory syndrome among children (MIS-C) has been linked to COVID-19, and it affects multiple organ systems in the body, including the gastrointestinal system. In present case report, a 14-year-old girl presented with clinico-laboratory and imaging evidence of acute pancreatitis but did not respond to the standard line of management for pancreatitis. Later, the laboratory investigations pointed to the diagnosis of MIS-C. She responded well to a pulse doses of methylprednisolone therapy. Acute pancreatitis as a lone manifestation of MIS-C poses a diagnostic challenge for paediatricians, and one should suspect MIS-C in acute non-responding pancreatitis.

Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis

BackgroundHypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAFARDS) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype.MethodsWe studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAFARDS in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support.ResultsThe PAFARDS was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p < 0.001). Respiratory failure was the most common cause of death in hypoinflammatory sepsis, whereas circulatory shock was the most common cause in hyperinflammatory sepsis. Death with severe underlying comorbidities was more frequent in hypoinflammatory sepsis (81% vs. 67%, p = 0.004).ConclusionsThe PAFARDS is modest in both phenotypes whereas primary cause of death among patients with sepsis differed substantially by phenotype. This study identifies challenges in powering future clinical trials to detect changes in mortality outcomes among patients with sepsis and ARDS.

Perioperative anaphylaxis: updates on pathophysiology.

Perioperative anaphylaxis has historically been attributed to IgE/FcεRI-mediated reactions; there is now recognition of allergic and nonallergic triggers encompassing various reactions beyond IgE-mediated responses. This review aims to present recent advancements in knowledge regarding the mechanisms and pathophysiology of perioperative anaphylaxis. Emerging evidence highlights the role of the mast-cell related G-coupled protein receptor X2 pathway in direct mast cell degranulation, shedding light on previously unknown mechanisms. This pathway, alongside traditional IgE/FcεRI-mediated reactions, contributes to the complex nature of anaphylactic reactions. Investigations into the microbiota-anaphylaxis connection are ongoing, with potential implications for future treatment strategies. While serum tryptase levels serve as mast cell activation indicators, identifying triggers remains challenging. A range of mediators have been associated with anaphylaxis, including vasoactive peptides, proteases, lipid molecules, cytokines, chemokines, interleukins, complement components, and coagulation factors. Further understanding of clinical endotypes and the microenvironment where anaphylactic reactions unfold is essential for standardizing mediator testing and characterization in perioperative anaphylaxis. Ongoing research aims to elucidate the mechanisms, pathways, and mediators involved across multiple organ systems, including the cardiovascular, respiratory, and integumentary systems, which will be crucial for improving patient outcomes.

Borrelia burgdorferi

Since its recent discovery in the late 1970s, Lyme Disease (LD) has been a growing public health concern, especially in the United States where it accounts for the majority of vector-borne infections each year. The causative agent, Borrelia burgdorferi, is transmitted to humans through the bite of an infected Ixodes tick. This pathogen uses many unique mechanisms to both shield itself from the host immune response and cause disease. Clinically, LD presents in successive phases, with each increasing in severity as the bacterial cells migrate to new tissues and organ systems. On the epidemiological and ecological fronts, limitations in reporting, ecological changes, and a lack of public support hinder accurate surveillance and enhance the spread of the disease. The goal of this literature review is to increase public knowledge of B. burgdorferi, its vector, and the disease it causes, along with suggesting preventative measures to protect individuals who reside in high-risk areas. A collective and coordinated public health effort represents our greatest chance of restraining the LD-causing pathogen.

Treatment of mice with maternal intermittent fasting to improve the fertilization rate and reproduction.

Maternal intermittent fasting (MIF) can have significant effects on several tissue and organ systems of the body, but there is a lack of research on the effects on the reproductive system. So, the aim of our study was to analyze the effects of MIF on fertility. B6C3F1Crl (C57BL/6N × C3H/HeN) male and female mice were selected for the first part of the experiments and were analyzed for body weight and fat weight after administration of the MIF intervention, followed by analysis of sperm counts and activation and embryo numbers. Subsequently, two strains of mice, C57BL/6NCrl and BALB/cJRj, were selected and administered MIF to observe the presence or absence of vaginal plugs for the purposes of mating success, sperm and oocyte quality, pregnancy outcome, fertility status and in vitro fertilization (IVF). Our results showed a significant reduction in body weight and fat content in mice receiving MIF intervention in B6C3F1Crl mice. Comparing the reproduction of the two strains of mice. However, the number of litters was increased in all MIF interventions in C57BL/6NCrl, but not statistically significant. In BALB/cJRj, there was a significant increase in the number of pregnant females as well as litter size in the MIF treatment group, as well as vaginal plugs, and IVF. There was also an increase in sperm activation and embryo number and the MIF intervention significantly increased sperm count and activation. Our results suggest that MIF interventions may be beneficial for reproduction in mice.

CD4 expression on monocytes correlates with recovery from multiple organ dysfunction syndrome and mortality in patients with septic shock

BackgroundTo date, the correlation between CD4 on the monocytes (mCD4) expression and the prognosis of patients with septic shock remains unclear. The purpose of this study was to analyze the expression of mCD4 in these patients and further evaluate whether mCD4 expression correlates with either the recovery from multiple organ dysfunction syndrome (MODS) or mortality.MethodsThe study participants were recruited from a tertiary general hospital in China (Affiliated Dongyang Hospital of Wenzhou Medical University). Sepsis and septic shock were diagnosed based on the diagnostic criteria of Sepsis-3. MODS was defined as a Sequential Organ Failure Assessment score of at least two organ systems ≥2. Persistent MODS was defined as the continual meeting of the MODS criteria when re-evaluated one week after admission (day 7). A logistic regression model was used to test whether mCD4 was an independent prognostic factor for mortality in patients with septic shock. A paired sample rank sum test was used to examine the correlation between mCD4 expression and MODS recovery.ResultThe study recruited 79 patients with septic shock as the study group, 74 patients with sepsis as the disease control group, and 56 volunteers as healthy controls. In the first 24 h after admission (day 1), mCD4 expression was significantly reduced in patients with septic shock compared to healthy controls and patients with sepsis. Moreover, mCD4 expression was an independent prognostic factor for in-hospital and 28 day mortality in patients with septic shock. mCD4 expression did not show significant differences in patients with persistent MODS on day 7 compared to day 1. However, mCD4 expression was significantly higher in patients without persistent MODS on day 7 than on day 1.ConclusionmCD4 expression is significantly reduced in patients with septic shock, which is an independent prognostic factor for mortality and closely related to recovery from MODS.

Animal sentience: The science and its implications, with particular reference to farmed animals

AbstractThere is an increasing amount of scientific research into animal sentience. Many scientists are studying the cognitive, emotional, and communicative capacities of a range of animals. The results of this research have led to a number of legal recognitions of the sentience of a range of animals. In 1997, the European Union (EU) gave legal recognition to the sentience of animals and updated and elevated this recognition in the Treaty of Lisbon. Other countries and states as well as the World Organization for Animal Health (WOAH, formerly OIE) have followed it. Scientists are increasingly acknowledging that sentience and emotion have arisen in a wide range of species. Research now emphasizes that there is an extraordinary variation in how different animal species (such as mammals, birds, fish, or insects) perceive the world and their environment. This paper looks at the sentience of the main farmed land and aquatic animals and the implications of this for how such animals are bred and housed. The paper concludes that intensive farming systems deprive animals of opportunities for positive emotions, such as play, exploration, social interaction, and feeding to satiation, and stops them from satisfying naturally motivated behaviors. To truly respect animal sentience, production systems should be designed with the animal's characteristics and needs in mind. The authors conclude that regenerative, agroecological, or organic farming systems better protect and respect the sentience of animals leading to less suffering and more opportunities for positive experiences.

Acute pancreatitis associated with pleural effusion: MDCT manifestations and anatomical basis.

Acute pancreatitis (AP) is a severe condition with complications that can impact multiple organ systems throughout the body. Specifically, the diffusion of peripancreatic effusion to the pleural cavity is a significant phenomenon in AP. However, its pathways and implications for disease severity are not fully understood. This study aims to investigate the anatomical routes of peripancreatic effusion diffusion into the pleural cavity in patients with AP and to analyze the correlation between the severity of pleural effusion (PE) and the computed tomography severity index (CTSI) and acute physiology and chronic health evaluation II (APACHE II) scoring system. 119 patients with AP admitted to our institution were enrolled in this study (mean age 50 years, 74 male and 45 female). Abdominal CT was performed, and the CTSI and APACHE II index were used to evaluate the severity of the AP, Meanwhile, the prevalence and semiquantitative of PE were also mentioned. The anatomical pathways of peripancreatic effusion draining to pleural were analyzed. Finally, the correlation relationship between the severity of AP and the PE was analyzed. In 119 patients with AP, 74.8% of patients had PE on CT. The anatomic pathways of peripancreatic effusion draining to pleural included esophageal hiatus in 33.7% of patients, aortic hiatus in 6.7% of patients and inferior vena cava hiatus in 3.37% of patients. The rating of PE on CT was correlated with CTSI scores (r= 0.449, P= 0.000) and was slightly correlated with the APACHE II scores (r= 0.197, P= 0.016). PE is a common complication of AP, which can be caused by anatomic pathways such as diaphragmatic hiatus. Due to its correlation with the CTSI score, the PE may be a supplementary indicator in determining the severity of AP.

Frequency of concurrent lesions in feedlot mortalities at necropsy

Feedlot mortalities continue to be a major economic issue for cattle producers. Necropsies have been utilized to help diag­nose disease processes in commercial feedlots. However, iden­tification of concurrent diagnoses and multiple-affected organ systems have been rarely recorded. The study objective was to determine the frequency and most common combinations of concurrent lesions and multiple-affected organ systems in feed­lot mortalities.

Tiny Organs, Big Impact: How Microfluidic Organ-on-Chip Technology Is Revolutionizing Mucosal Tissues and Vasculature

Organ-on-chip (OOC) technology has gained importance for biomedical studies and drug development. This technology involves microfluidic devices that mimic the structure and function of specific human organs or tissues. OOCs are a promising alternative to traditional cell-based models and animals, as they provide a more representative experimental model of human physiology. By creating a microenvironment that closely resembles in vivo conditions, OOC platforms enable the study of intricate interactions between different cells as well as a better understanding of the underlying mechanisms pertaining to diseases. OOCs can be integrated with other technologies, such as sensors and imaging systems to monitor real-time responses and gather extensive data on tissue behavior. Despite these advances, OOCs for many organs are in their initial stages of development, with several challenges yet to be overcome. These include improving the complexity and maturity of these cellular models, enhancing their reproducibility, standardization, and scaling them up for high-throughput uses. Nonetheless, OOCs hold great promise in advancing biomedical research, drug discovery, and personalized medicine, benefiting human health and well-being. Here, we review several recent OOCs that attempt to overcome some of these challenges. These OOCs with unique applications can be engineered to model organ systems such as the stomach, cornea, blood vessels, and mouth, allowing for analyses and investigations under more realistic conditions. With this, these models can lead to the discovery of potential therapeutic interventions. In this review, we express the significance of the relationship between mucosal tissues and vasculature in organ-on-chip (OOC) systems. This interconnection mirrors the intricate physiological interactions observed in the human body, making it crucial for achieving accurate and meaningful representations of biological processes within OOC models. Vasculature delivers essential nutrients and oxygen to mucosal tissues, ensuring their proper function and survival. This exchange is critical for maintaining the health and integrity of mucosal barriers. This review will discuss the OOCs used to represent the mucosal architecture and vasculature, and it can encourage us to think of ways in which the integration of both can better mimic the complexities of biological systems and gain deeper insights into various physiological and pathological processes. This will help to facilitate the development of more accurate predictive models, which are invaluable for advancing our understanding of disease mechanisms and developing novel therapeutic interventions.

Extracardiac Manifestations Fail to Predict the Severity of Cardiac Phenotype in Children and Young Adults with Marfan Syndrome.

We performed a secondary analysis of the Pediatric Heart Network (PHN) Marfan Trial public-use database to evaluate associations between extracardiac features and cardiac and aortic phenotypes in study participants. Aortic aneurysm phenotype was defined as aortic root Z-score ≥4.5, aortic root growth rate ≥75th percentile, aortic dissection, and aortic surgery. Severe cardiac phenotype was defined as aortic dissection, aortic Z-score ≥4.5, aortic valve surgery, at least moderate mitral regurgitation, mitral valve surgery, left ventricular dysfunction, or death. Extracardiac manifestations were characterized by specific organ system involvement and by a novel aggregate extracardiac score (AES) that was created for this study based on the original Ghent nosology. Mixed effects logistic regression analysis compared AES and systems involvement to outcomes. Of 608 participants (60% male), the median age at enrollment was 10.8years (interquartile range: 6, 15.4). Aortic aneurysm phenotype was observed in 71% of participants and 64% had severe cardiac phenotype. On univariable analysis, skeletal (OR: 1.95, 95% CI: 1.01, 3.72; p = 0.05), skin manifestation (OR: 1.62, 95% CI: 1.13, 2.34; p = 0.01) and AES (OR: 1.17, 95% CI: 1.02, 1.34; p = 0.02) were associated with aortic aneurysm phenotype but were not significant in multivariable analysis. There was no association between extracardiac manifestations and severe cardiac phenotype. Thus, the severity of cardiac manifestations in Marfan syndrome (MFS) was independent of extracardiac phenotype and AES. Severity of extracardiac involvement did not appear to be a useful clinical marker for cardiovascular risk-stratification in this cohort of children and young adults with MFS.

Soil characteristics and management system influence weed–crop competition

AbstractThe resource pool diversity hypothesis (RPDH) posits that organic systems that include diverse crop rotations, green manure and organic fertilizers have a greater diversity of resource pools that can alleviate weed–crop competition compared to conventional systems. To test the RPDH, wheat (Triticum aestivum) and wild oats (Avena sterilis) in winter, and maize (Zea mays) and Palmer amaranth (Amaranthus palmeri) in summer, were grown in pots in soils from organic (ORG) and conventional (CONV) fields, with contrasting number of estimated resource pools. A replacement series design with proportions of crop: weed of 0:1, 0.25:0.75, 0.5:0.5, 0.75:0.25 and 1:0 was used. Half of the pots received an organic‐mineral fertilizer (F) and the other half did not (NF). Aerial biomass of all plants was measured. Relative Crowding Coefficient (RCC) and the product of RCC (RCCP) for each crop and weed biomass were estimated by modelling the biomass across crop: weed proportions. RCCP larger than one was used as an indicator of overyielding. In the winter experiment, wheat always outcompeted wild oats and we did not detect overyielding across fields with different number of pools, system or fertilizer. In the summer experiment, we found overyielding in ORG NF fields. Functionally different species like maize and Palmer amaranth may have been extracting nutrients from diverse pools in organic NF fields whereas with the addition of fertilizer, Palmer amaranth outcompeted maize. Biomass of monoculture crop and weed in both experiments were positively correlated with number of estimated pools, even if none of the competition indexes were. Our results provide some support for the RPHD in species that are functionally different but also question the definition and nature of the nutrient pools, as well as emphasize the need for more research in the area.

Conventional or organic cattle farming? Trade-offs between crop yield, livestock capacity, organic premiums, and government payments

CONTEXTAn important question for farmers is whether to run their farm conventionally or organically. This choice can significantly affect the farm's financial performance and its impact on the environment. OBJECTIVEThe primary objective of this study is to compare the profitability of conventional and organic cattle systems and investigate how it is associated with individual farm characteristics, like forage production capacity, forage quality, milk quota, animal housing capacity, and their relative presences. METHODWe employ a whole farm optimization model, customized for Norwegian cattle farming. The primary goal of this model is to maximize the gross margin by optimizing decisions related to land usage and animal inventory while adhering to a set of constraints. We systematically solve more than 200,000 model instances, with varying farm characteristics. RESULTS AND CONCLUSIONSThe results can be distilled to the following key points: If forage of good quality is readily available, but the livestock operation cannot be expanded due to animal housing and milk quota restrictions, organic may outcompete conventional farming. Otherwise, gross margin is maximized with conventional farming. These findings emphasize the crucial role of forage production capacity and quality in relation to available milk quota and infrastructure when considering the transition from conventional to organic farming. Extensive sensitivity analyses affirm the robustness of these conclusions. Regional regulatory factors, such as government farm payments, also play a significant role, and influence the optimal farming approach. Additionally, we show that increases in organic price premiums can markedly impact the competitiveness of organic farming, even in a system where government payments make out a significant part of the farm revenue. SIGNIFICANCEThe model can support farmers to make informed decisions about converting to organic or conventional farming. It can also be used by policymakers to determine the level of support required to make it worthwhile for different types of farms to convert. We also show that existing government payment schemes give rise to regional differences in the incentives for organic farming in Norway. To ensure equal incentives for organic farming across the country, the organic payments would have to be regionally adjusted, in line with the other already regionally dependent government payments. This insight may be of significant interest to policymakers and other stakeholders.

CRISPR-Based Gene Therapies: From Preclinical to Clinical Treatments

In recent years, clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) protein have emerged as a revolutionary gene editing tool to treat inherited disorders affecting different organ systems, such as blood and muscles. Both hematological and neuromuscular genetic disorders benefit from genome editing approaches but face different challenges in their clinical translation. The ability of CRISPR/Cas9 technologies to modify hematopoietic stem cells ex vivo has greatly accelerated the development of genetic therapies for blood disorders. In the last decade, many clinical trials were initiated and are now delivering encouraging results. The recent FDA approval of Casgevy, the first CRISPR/Cas9-based drug for severe sickle cell disease and transfusion-dependent β-thalassemia, represents a significant milestone in the field and highlights the great potential of this technology. Similar preclinical efforts are currently expanding CRISPR therapies to other hematologic disorders such as primary immunodeficiencies. In the neuromuscular field, the versatility of CRISPR/Cas9 has been instrumental for the generation of new cellular and animal models of Duchenne muscular dystrophy (DMD), offering innovative platforms to speed up preclinical development of therapeutic solutions. Several corrective interventions have been proposed to genetically restore dystrophin production using the CRISPR toolbox and have demonstrated promising results in different DMD animal models. Although these advances represent a significant step forward to the clinical translation of CRISPR/Cas9 therapies to DMD, there are still many hurdles to overcome, such as in vivo delivery methods associated with high viral vector doses, together with safety and immunological concerns. Collectively, the results obtained in the hematological and neuromuscular fields emphasize the transformative impact of CRISPR/Cas9 for patients affected by these debilitating conditions. As each field suffers from different and specific challenges, the clinical translation of CRISPR therapies may progress differentially depending on the genetic disorder. Ongoing investigations and clinical trials will address risks and limitations of these therapies, including long-term efficacy, potential genotoxicity, and adverse immune reactions. This review provides insights into the diverse applications of CRISPR-based technologies in both preclinical and clinical settings for monogenic blood disorders and muscular dystrophy and compare advances in both fields while highlighting current trends, difficulties, and challenges to overcome.

Association between immune-related adverse events and prognosis in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) provides a variety of options for patients with advanced non-small-cell lung cancer (NSCLC). After the application of ICIs, the immune system of patients was highly activated, and immune-related adverse events (irAEs) could occur in some organ systems, and irAEs seemed to be associated with the survival prognosis of patients. Therefore, we evaluated the association between survival outcomes and irAEs in NSCLC patients and conducted a systematic review and meta-analysis.MethodsWe conducted systematic reviews of PubMed, Embase, Cochrane, and Web of Science databases until December 2021. The forest map was constructed by combining the hazard ratio (HR) and 95% confidence interval (CI). I2 estimated the heterogeneity between studies. A meta-analysis was performed using R 4.2.1 software.ResultsEighteen studies included 4808 patients with advanced NSCLC. In pooled analysis, the occurrence of irAEs was found to be a favorable factor for improved prognosis (PFS: HR: 0.48, 95% CI: 0.41-0.55, P &amp;lt;0.01; OS: HR: 0.46, 95% CI: 0.42-0.52, P &amp;lt;0.01). In subgroup analyses, cutaneous irAE, gastrointestinal irAE, endocrine irAE and grade ≥3 irAEs were associated with improvements in PFS and OS, but pulmonary and hepatic irAEs were not.ConclusionExisting evidence suggests that the occurrence of irAEs may be a prognostic biomarker for advanced NSCLC. However, further research is needed to explore the prospect of irAEs as a prognostic biomarker in patients undergoing immunotherapy.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPEROFILES/405333_STRATEGY_20240502.pdf, identifier CRD42023405333.

Numerical analysis-based performance assessment of the small-scale organic Rankine cycle turbine design for residential applications

The organic Rankine cycle (ORC) is one of the most common ways to use energy resources to utilise waste heat. Integrating ORC with other systems, such as cooling or heating applications, is also helpful for residential uses. In the ORC system, the turbines are the most critical component determining the system's efficiency. This study conducted a computational fluid dynamics study on a regenerative flow turbine that can be used in small-scale organic Rankine cycle systems. For the higher temperature applications, the analyses were performed using n-pentane working fluid for 1500 and 3000 rpm turbine speeds, inlet temperature between 475–550 K, outlet pressure between 0.9–1.2 MPa, and mass flow rates between 0.5–1.0 kg/s. As a result of the analysis, the isentropic efficiency varies between 4.97 % and 12.52 %. It was concluded that the output power obtained from the turbine varies between 0.53 kW and 2.96 kW. The analyses were also performed for lower temperature (363 and 393 K), pressure (0.05 MPa and 0.3 MPa) and mass flows (0.1 to 0.25 kg/s) applications. In this case, the isentropic efficiency of the turbine varies between 6.23 % and 14.52 %, whereas the power generation varies between 0.068 and 0.521 kW.

Effects of management practices on the ecosystem-service multifunctionality of temperate grasslands

Human wellbeing depends on ecosystem services, highlighting the need for improving the ecosystem-service multifunctionality of food and feed production systems. We study Swiss agricultural grasslands to assess how employing and combining three widespread aspects of grassland management and their interactions can enhance 22 plot-level ecosystem service indicators, as well as ecosystem-service multifunctionality. The three management aspects we assess are i) organic production system, ii) an eco-scheme prescribing extensive management (without fertilization), and iii) harvest type (pasture vs. meadow). While organic production system and interactions between the three management aspects play a minor role, the main effects of eco-scheme and harvest type considerably shape single services. Moreover, the eco-scheme ‘extensive management’ and the harvest type ‘pasture’ enhance plot-scale ecosystem-service multifunctionality, mostly through facilitating cultural services at the expense of provisioning services. These changes in ecosystem-service supply occur mainly via changes in land-use intensity, i.e., reduced fertilizer input and harvest frequency. In conclusion, diversifying grassland management where this is currently homogeneous across farms and landscapes depicts an important first step to improve landscape-scale multifunctionality for sustainable grassland systems. To meet societal ecosystem services demand, the three studied management aspects can be systematically combined to increase ecosystem services that are in short supply.

Reverse engineering morphogenesis through Bayesian optimization of physics-based models

Morphogenetic programs coordinate cell signaling and mechanical interactions to shape organs. In systems and synthetic biology, a key challenge is determining optimal cellular interactions for predicting organ shape, size, and function. Physics-based models defining the subcellular force distribution facilitate this, but it is challenging to calibrate parameters in these models from data. To solve this inverse problem, we created a Bayesian optimization framework to determine the optimal cellular force distribution such that the predicted organ shapes match the experimentally observed organ shapes. This integrative framework employs Gaussian Process Regression, a non-parametric kernel-based probabilistic machine learning modeling paradigm, to learn the mapping functions relating to the morphogenetic programs that maintain the final organ shape. We calibrated and tested the method on Drosophila wing imaginal discs to study mechanisms that regulate epithelial processes ranging from development to cancer. The parameter estimation framework successfully infers the underlying changes in core parameters needed to match simulation data with imaging data of wing discs perturbed with collagenase. The computational pipeline identifies distinct parameter sets mimicking wild-type shapes. It enables a global sensitivity analysis to support the regulation of actomyosin contractility and basal ECM stiffness to generate and maintain the curved shape of the wing imaginal disc. The optimization framework, combined with experimental imaging, identified that Piezo, a mechanosensitive ion channel, impacts fold formation by regulating the apical-basal balance of actomyosin contractility and elasticity of ECM. This workflow is extensible toward reverse-engineering morphogenesis across organ systems and for real-time control of complex multicellular systems.

Performance and mechanism of organic solid-phase sediment composite plugging agent

The surface pipeline sediments of the Yingmai and Hade oil fields mainly contain substances such as asphalt and paraffin. The formation of sediment can increase the backpressure during pipeline transportation, and in severe cases, it can also lead to pipeline blockage. In order to solve this on-site situation, indoor experiments were conducted in the early stage, and an efficient organic unblocking system LXW was optimized and formulated. Based on this system, this article selects the wire mesh filtration method to evaluate the unblocking performance of LXW and on-site unblocking agents in the study and comparison of three evaluation methods. At the same time, based on the analysis of the chemical composition, microstructure, and melting point of organic sediments, from the perspectives of safety, environmental protection, and economic factors, further compares the performance and universality of the three unblocking systems, optimizes the process parameters of the LXW unblocking system, explores its stability and impact on the demulsification and dehydration of crude oil emulsions, and evaluates its safety performance. The LXW unblocking system has a more efficient unblocking effect and better universality, which can solve the problem of multiple block blockages on site. In addition, compared with existing unblocking agents, it has better economic benefits and is in line with the characteristics of low cost on site. On this basis, the dissolution and dispersion mechanism of the blockage system on sediment was studied through laser scattering system and fluorescence microscope, and its microscopic mechanism was further verified. At the same time, the oil-water interfacial tension under the action of the unblocking system was studied, and it was found that adding the agent can significantly reduce the equilibrium interfacial tension, which is of great significance for increasing production and injection.

Emerging Vistas for the Nutraceutical Withania somnifera in Inflammaging

Inflammaging, a coexistence of inflammation and aging, is a persistent, systemic, low-grade inflammation seen in the geriatric population. Various natural compounds have been greatly explored for their potential role in preventing and treating inflammaging. Withania somnifera has been used for thousands of years in traditional medicine as a nutraceutical for its numerous health benefits including regenerative and adaptogenic effects. Recent preclinical and clinical studies on the role of Withania somnifera and its active compounds in treating aging, inflammation, and oxidative stress have shown promise for its use in healthy aging. We discuss the chemistry of Withania somnifera, the etiology of inflammaging and the protective role(s) of Withania somnifera in inflammaging in key organ systems including brain, lung, kidney, and liver as well as the mechanistic underpinning of these effects. Furthermore, we elucidate the beneficial effects of Withania somnifera in oxidative stress/DNA damage, immunomodulation, COVID-19, and the microbiome. We also delineate a putative protein–protein interaction network of key biomarkers modulated by Withania somnifera in inflammaging. In addition, we review the safety/potential toxicity of Withania somnifera as well as global clinical trials on Withania somnifera. Taken together, this is a synthetic review on the beneficial effects of Withania somnifera in inflammaging and highlights the potential of Withania somnifera in improving the health-related quality of life (HRQoL) in the aging population worldwide.