Function Of System Research Articles

A highly specific two-photon fluorescent probe for real-time monitoring of acetylcholinesterase in neurogenic disorders in vivo

Acetylcholinesterase (AChE) hydrolyses choline into thiocholine, which is essential for cholinergic neurons to revert to their resting state following activation. Abnormal changes in AChE activity can directly affect nervous system function. Thus, the specific detection of AChE activity is urgently needed for elucidating the function of the nervous system and diagnosing AChE-related diseases. Current methods for detecting AChE activity have several limitations, including strong background interference and poor tissue penetration. Thus, we designed and synthesized a two-photon (TP) excited fluorescent probe, WZ-AChE, for the specific detection of AChE. Briefly, a carbamate bond was chosen to specifically recognize AChE, which can also be cleaved by AChE. The product, WZ, released strong deep red fluorescence signal under TP excitation at 800 nm. Our results showed that WZ-AChE can detect AChE activity in PC12 cells with both superior sensitivity and selectivity. In addition, we successfully applied WZ-AChE to a C. elegans Parkinson's disease (PD) model and a mouse model of depression. The findings revealed that AChE activity was greater in both disease models than in the control group. To summarize, a novel tool was created to investigate the mechanisms underlying PD and depression.

Efficacy of combined use of octreotide and sodium tanshinone IIA sulfonate in patients with cirrhosis complicated with severe acute pancreatitis

Purpose: To assess the prognosis of liver cirrhosis complicated with severe acute pancreatitis (SAP) after treatment with octreotide in combination with sodium tanshinone IIA sulfonate. Methods: A total of 164 patients with cirrhosis complicated with SAP were randomly assigned to two groups, each with 82 patients. Serum levels of inflammatory factors, as well as vascular endothelial function and liver function indices were determined. Treatment outcomes in the patients were recorded in terms of abdominal pain relief time, gastrointestinal function recovery time, hospital stay duration, and incidence of complications. Results: Relative to the control group, there were decreases in concentrations of inflammatory indices in the study cohort. Endothelial function index levels increased in the two groups, but the levels of endothelin (ET) and von Willebrand Factor (vWF) decreased more in the study group of patients, when compared to the control group, while nitric oxide (NO) level was raised (p < 0.05). Liver function improved in both groups. There were marked reductions in serum ALT, AST and total bilirubin (TBIL) in study cohort, relative to the control cohort (p < 0.05). However, albumin (ALB) levels were comparable in the two groups. Abdominal pain relief time, duration of hospitalization and time taken for normal digestive system function were shorter in the study cohort (p < 005). Receiver operating characteristic (ROC) curve analysis revealed that after treatment with octreotide and sodium tanshinone IIA sulfonate, values of area under the curve (AUC) for abdominal pain relief time, gastrointestinal function recovery time and hospital stay were 0.886, 0.918 and 0.794, respectively. Conclusion: The combined use of octreotide and sodium tanshinone IIA sulfonate inhibits the release of inflammatory factors in cirrhotic patients with SAP, and improves vascular endothelial and liver functions, thereby improving disease prognosis. These data constitute a good scientific basis for the use of octreotide and sodium tanshinone IIA sulfonate in the treatment of liver cirrhosis complicated with SAP.

All-In-One Optoelectronic Transistors for Bio-Inspired Visual System.

Visual perception has profound effects on human decision-making and emotional responses. Replicating the functions of the human visual system through device development has been a constant pursuit in recent years. However, to fully simulate the various functions of the human visual system, it is often necessary to integrate multiple devices with different functions, resulting in complex, large-volume device structures and increased power consumption. Here, an optoelectronic transistor with comprehensive visual functions is introduced. By coupling diverse photoreceptive properties of the channel and electrical regulation through charge injection/ferroelectric switching from the hafnium-based gate, the devices can simulate functions of both photoreceptors in the retina and synapses in the visual cortex. A device array is constructed to confirm the perceptual functions of cone and rod cells. Subsequently, color discrimination and recognition for color images are achieved by combining the tunable perception and synapse functions. Then an intelligent traffic judgment system with this all-in-one device is developed, which is capable of making judgments and decisions regarding traffic signals and pedestrian movements. This work provides a potential solution for developing compact and efficient devices for the next-generation bio-inspired visual system.

Mitochondria in tumor immune surveillance and tumor therapies targeting mitochondria.

Mitochondria play a central role in cellular energy production and metabolic regulation, and their function has been identified as a key factor influencing tumor immune responses. This review provides a comprehensive overview of the latest advancements in understanding the role of mitochondria in tumor immune surveillance, covering both innate and adaptive immune responses. Specifically, it outlines how mitochondria influence the function of the tumor immune system, underscoring their crucial role in modulating immune cell behavior to either promote or inhibit tumor development and progression. Additionally, this review highlights emerging drug interventions targeting mitochondria, including novel small molecules with significant potential in cancer therapy. Through an in-depth analysis, it explores how these innovative strategies could improve the efficacy and outlook of tumor treatment.

Block Medcare: Advancing Healthcare Through Blockchain Integration

In an era driven by information exchange, transparency and security hold crucial importance, particularly within the healthcare industry, where data integrity and confidentiality are paramount. This paper investigates the integration of blockchain technology in healthcare, focusing on its potential to revolutionize Electronic Health Records (EHR) management and data sharing. By leveraging Ethereum-based blockchain implementations and smart contracts, we propose a novel system that empowers patients to securely store and manage their medical data. Our research addresses critical challenges in implementing blockchain in healthcare, including scalability, user privacy, and regulatory compliance. We propose a solution that combines digital signatures, Role-Based Access Control, and a multi-layered architecture to enhance security and ensure controlled access. The system's key functions, including user registration, data append, and data retrieval, are facilitated through smart contracts, providing a secure and efficient mechanism for managing health information. To validate our approach, we developed a decentralized application (dApp) that demonstrates the practical implementation of our blockchain-based healthcare solution. The dApp incorporates user-friendly interfaces for patients, doctors, and administrators, showcasing the system's potential to streamline healthcare processes while maintaining data security and integrity. Additionally, we conducted a survey to gain insights into the perceived benefits and challenges of blockchain adoption in healthcare. The results indicate strong interest among healthcare professionals and IT experts, while also highlighting concerns about integration costs and technological complexity. Our findings underscore the transformative potential of blockchain technology in healthcare, pointing towards a new era of patient-centric and secure healthcare services. By addressing current limitations and exploring future enhancements, such as integration with IoT devices and AI-driven analytics, this research contributes to the ongoing evolution of secure, efficient, and interoperable healthcare systems.

Generative AI-based knowledge graphs for the illustration and development of mHealth self-management content.

Digital therapeutics (DTx) in the form of mobile health (mHealth) self-management programs have demonstrated effectiveness in reducing disease activity across various diseases, including fibromyalgia and arthritis. However, the content of online self-management programs varies widely, making them difficult to compare. This study aims to employ generative artificial intelligence (AI)-based knowledge graphs and network analysis to categorize and structure mHealth content at the example of a fibromyalgia self-management program. A multimodal mHealth online self-management program targeting fibromyalgia and post-viral fibromyalgia-like syndromes was developed. In addition to general content, the program was customized to address specific features and digital personas identified through hierarchical agglomerative clustering applied to a cohort of 202 patients with chronic musculoskeletal pain syndromes undergoing multimodal assessment. Text files consisting of 22,150 words divided into 24 modules were used as the input data. Two generative AI web applications, ChatGPT-4 (OpenAI) and Infranodus (Nodus Labs), were used to create knowledge graphs and perform text network analysis, including 3D visualization. A sentiment analysis of 129 patient feedback entries was performed. The ChatGPT-generated knowledge graph model provided a simple visual overview with five primary edges: "Mental health challenges", "Stress and its impact", "Immune system function", "Long COVID and fibromyalgia" and "Pain management and therapeutic approaches". The 3D visualization provided a more complex knowledge graph, with the term "pain" appearing as the central edge, closely connecting with "sleep", "body", and "stress". Topical cluster analysis identified categories such as "chronic pain management", "sleep hygiene", "immune system function", "cognitive therapy", "healthy eating", "emotional development", "fibromyalgia causes", and "deep relaxation". Gap analysis highlighted missing links, such as between "negative behavior" and "systemic inflammation". Retro-engineering of the self-management program showed significant conceptual similarities between the knowledge graph and the original text analysis. Sentiment analysis of free text patient comments revealed that most relevant topics were addressed by the online program, with the exception of social contacts. Generative AI tools for text network analysis can effectively structure and illustrate DTx content. Knowledge graphs are valuable for increasing the transparency of self-management programs, developing new conceptual frameworks, and incorporating feedback loops.

7942 Evolution of Insulin, Insulin-like Growth Factor and Their Cognate Receptors in Vertebrates, Invertebrates and Viruses

Abstract Disclosure: M. Chrudinova: None. Y.D. Dogru: None. R. Huang: None. R. Reiners: None. P. De Meyts: None. J. DaCosta: None. E. Altindis: None. The insulin/insulin-like growth factor (IGF) signaling system is an evolutionarily conserved system and controls central processes including metabolism, cellular growth, proliferation, and differentiation in vertebrates. On the other hand, invertebrate insulin-like peptides (ILPs) regulate growth, stress responses, longevity and sex-related functions. In addition, we recently showed that six viruses possess viral insulin-like peptides (VILPs) that can bind to the receptors and stimulate post-receptor signaling. The evolution of these hormones and the origin of VILPs are not completely understood. Here, we collected vertebrate and invertebrate insulin, IGF and their cognate receptor sequences to analyze their evolutionary relations. We analyzed 177 vertebrate insulins, 119 vertebrate IGF-1s, 127 vertebrate IGF-2s, 197 invertebrate ILPs and 6 viral insulin/IGF-1 like peptides. We also analyzed 214 insulin receptor (IR), 160 IGF receptor (IGF1R) and 39 invertebrate receptor sequences to identify conservation and the evolutionary trajectory to reveal conserved motifs. Through phylogenetic analyses, we observed a separate branching of invertebrate ILPs and vertebrate insulins, IGF-1s and IGF-2s with notable exceptions including VILPs. IGF-1 and IGF-2 ligands were evolutionally better conserved compared to insulin ligands. Insulin C-peptide which is processed and cleaved was not well conserved compared to the functional A- and B-chain residues. In contrast, C-peptide of IGF-1 that plays an important role in receptor binding was very well conserved. IGF-1 C-domain showed higher variability in IGF1R binding residues compared to the A and B-domains, while residues important for binding of IGF-2 to IGF1R were well conserved. Insulin residues interacting with IR binding Site 1 were more conserved than those interacting with IR binding Site 2, while residues important for insulin dimerization and hexamerization residues are well conserved across species. We also showed that VILPs contain 14 amino acids that are conserved in insulin and IGFs, indicating their functional importance. Phylogenetic relationships of the receptor sequences suggest vertebrate IRs and IGF1Rs evolved from a common ancestor during early vertebrate evolution. Interestingly, receptor subunits revealed a closer relation of amphibian IR α-subunits to Mammalia IR α-subunits than Aves and Reptilians. The conservation rate of receptor residues essential for ligand-receptor interaction revealed that these residues are best conserved in the L1 domain for IR and IGF1R, with a higher rate of variation in other domains for both receptors. Taken together, our study provides a comprehensive analysis of insulin, IGFs, VILPs and their cognate receptors’ evolution, and opens new avenues to better understand the evolution, function, and structure relations of this complex signaling system. Presentation: 6/3/2024

CYRAD: a translational study assessing immune response to radiotherapy by photons or protons in postoperative head and neck cancer patients through circulating leukocyte subpopulations and cytokine levels

BackgroundRadiotherapy has both immunostimulant and immunosuppressive effects, particularly in radiation-induced lymphopenia. Proton therapy has demonstrated potential in mitigating this lymphopenia, yet the mechanisms by which different types of radiation affect the immune system function are not fully characterized. The Circulating Immunes Cells, Cytokines and Brain Radiotherapy (CYRAD) trial aims to compare the effects of postoperative X-ray and proton radiotherapy on circulating leukocyte subpopulations and cytokine levels in patients with head and neck (CNS and ear nose throat) cancer.MethodsCYRAD is a prospective, non-randomized, single-center non interventional study assessing changes in the circulating leukocyte subpopulations and cytokine levels in head and neck cancer patients receiving X-ray or proton radiotherapy following tumor resection. Dosimetry parameters, including dose deposited to organs-at-risk such as the blood and cervical lymph nodes, are computed. Participants undergo 29 to 35 radiotherapy sessions over 40 to 50 days, followed by a 3-month follow-up. Blood samples are collected before starting radiotherapy (baseline), before the 11th (D15) and 30th sessions (D40), and three months after completing radiotherapy. The study will be conducted with 40 patients, in 2 groups of 20 patients per modality of radiotherapy (proton therapy and photon therapy). Statistical analyses will assess the absolute and relative relationship between variations (depletion, recovery) in immune cells, biomarkers, dosimetry parameters and early outcomes.DiscussionPrevious research has primarily focused on radiation-induced lymphopenia, paying less attention to the specific impacts of radiation on different lymphoid and myeloid cell types. Early studies indicate that X-ray and proton irradiation may lead to divergent outcomes in leukocyte subpopulations within the bloodstream. Based on these preliminary findings, this study aims to refine our understanding of how proton therapy can better preserve immune function in postoperative (macroscopic tumor-free) head and neck cancer patients, potentially improving treatment outcomes.Protocol versionVersion 2.1 dated from January 18, 2023.Trial registrationThe CYRAD trial is registered from October 19, 2021, at the US National Library of Medicine, ClinicalTrials.gov ID NCT05082961.

Enhancing accuracy and robustness in FBS decoupling through Tikhonov regularization and unit balancing

Frequency-based Substructuring (FBS) enables the prediction of transfer functions for an assembled system based on those of a single-unit system. Conversely, FBS decoupling derives the frequency response function (FRF) of a single-unit system from the assembled system. This approach is valuable when obtaining the transfer functions of a system is challenging due to boundary conditions and deformation conditions. FBS decoupling can enhance accuracy by using additional indicator sensors. However, this often results in significant noise due to the ill-posed FRF matrix inversion. In this paper, Tikhonov regularization is employed to reduce noise-induced errors. Furthermore, this paper addresses the issue of inadequate Tikhonov regularization caused by the inherent scaling differences between the rotational and translational components within the FRF matrix. To rectify this challenge, a unit balancing method is proposed to mitigate the influence of scaling differences. This method enhances the accuracy and reliability of FRF matrix inversion processes, contributing to enhanced noise reduction and robustness in practical applications.

Factors associated with resorption of calcific deposits in the shoulder with extracorporeal shock wave therapy

BackgroundFocused extracorporeal shock wave therapy (FSWT) is effective for treating calcific tendinitis of the shoulder. However, only a few reports exist on the factors related to calcium resorption after FSWT. Thus, this study aimed to investigate the factors associated with calcium resorption. MethodsIn 117 shoulders with chronic calcific rotator cuff tendinitis, FSWT was administered nine times once every 2 weeks (a total of 16 weeks). After nine sessions of FSWT, the shoulders were radiographed and categorized into complete resorption (CR) and incomplete resorption (ICR) groups. Evaluated parameters included age, duration of disease, Gärtner classification, size of calcium deposits, presence of blood flow around calcium deposits using the Doppler function of the ultrasound imaging system, Japanese Orthopaedic Association (JOA) score, University of California at Los Angeles score, disability of the arm, shoulder, and hand (UCLA) score, and tenderness. ResultsThe CR group included 93 shoulders (79.4%) and the ICR group included 24 shoulders (20.6%). In the two-arm comparison, CR showed significantly longer disease duration (P=.012) and high tenderness (P=.0013). Blood flow around calcium deposits was observed in 79.5% of shoulders in the CR group (P<.0001) and 29.1% in the ICR group. Type 1 Gärtner classification (P=.0009) was observed in 28 shoulders (30.1%) in the CR group and 17 shoulders (70.8%) in the ICR group. The two groups had no significant differences in age, size of calcium deposits, JOA score, or UCLA score. Multiple logistic regression analysis was performed using the following items that showed significant differences: absence of blood flow (odds ratio [OR], 8.51, 95% confidence interval [CI]: 2.24–22.8), Gärtner classification (OR, 5.60, 95%CI: 1.73–13.3), and duration of disease (OR, 1.06, 95%CI: 0.97–1.26). Longer disease duration, Gärtner type 1, and absence of blood flow around calcium deposits resulted in difficulty in calcium resorption. ConclusionPatients with Gärtner type 1 with prolonged disease duration and absence of blood flow around calcium deposits may have difficulty in achieving complete resorption.

Theoretical and experimental analysis of a nonlinear vibro-acoustic energy sink

This study is concerned with the experimental and theoretical analysis of a vibroacoustic nonlinear system devoted to absorption application. Based on the nonlinear energy sink principle, the dynamics of the system is reduced to two coupled degrees of freedom, one of which exhibits nonlinear behavior due to a large displacement mechanism. The set-up allows for precisely characterizing the nonlinear function of the mechanical system, first uncoupled and then coupled with an acoustic and linear resonator. Continuation procedures are performed experimentally and numerically, respectively using a phase-locked loop (PLL) and the asymptotic numerical method implemented in the MANLAB software package. The comparison between theoretical predictions and experimental results obtained on the uncoupled system allows for a parameter identification of the nonlinear resonator. Measurements on the coupled system highlight the energy pumping phenomenon, which can be predicted from numerical predictions in which identified parameters are introduced. The procedure aims at proposing analytical models for achieving efficient level attenuation, and providing design guidelines for sound reduction at high levels in confined spaces.

Enhanced neural activity detection with microelectrode arrays modified by drug-loaded calcium alginate/chitosan hydrogel

Microelectrode arrays (MEAs) are pivotal brain-machine interface devices that facilitate in situ and real-time detection of neurophysiological signals and neurotransmitter data within the brain. These capabilities are essential for understanding neural system functions, treating brain disorders, and developing advanced brain-machine interfaces. To enhance the performance of MEAs, this study developed a crosslinked hydrogel coating of calcium alginate (CA) and chitosan (CS) loaded with the anti-inflammatory drug dexamethasone sodium phosphate (DSP). By modifying the MEAs with this hydrogel and various conductive nanomaterials, including platinum nanoparticles (PtNPs) and poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS), the electrical properties and biocompatibility of the electrodes were optimized. The hydrogel coating matches the mechanical properties of brain tissue more effectively and, by actively releasing anti-inflammatory drugs, significantly reduces post-implantation tissue inflammation, extends the electrodes' lifespan, and enhances the quality of neural activity detection. Additionally, this modification ensures high sensitivity and specificity in the detection of dopamine (DA), displaying high-quality dual-mode neural activity during in vivo testing and revealing significant functional differences between neuron types under various physiological states (anesthetized and awake). Overall, this study showcases the significant application value of bioactive hydrogels as excellent nanobiointerfaces and drug delivery carriers for long-term neural monitoring. This approach has the potential to enhance the functionality and acceptance of brain-machine interface devices in medical practice and has profound implications for future neuroscience research and the development of strategies for treating neurological diseases.

Pulmonary Hypertension: Pharmacological and Non-Pharmacological Therapies.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling, often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here, we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neurostimulation including acupuncture. Lastly, we also touch upon the disease's different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

The airway smooth muscle and the pipe dream of better bronchodilators.

Research on airway smooth muscle has traditionally focused on its putative detrimental role in asthma, emphasizing on how its shortening narrows the airway lumen, without much consideration about its potential role in subserving the function of the entire respiratory system. New experimental evidence on mice suggests that not only the smooth muscle is required to sustain life postnatally, but its stiffening effect on the lung tissue also protects against excessive airway narrowing and, most importantly, against small airway narrowing heterogeneity and closure. These results suggest that the smooth muscle plays an vital role in the lung periphery, essentially safeguarding alveolar ventilation by preventing small airway closure. These results also shed light on perplexing clinical observations, such as the long-standing doubts about the safety of bronchodilators. Since there seems to be an optimal level of smooth muscle contraction, at least in small airways, the therapeutic goal of maximizing the relaxation of the smooth muscle in asthma needs to be revisited. A bronchodilator with an excessive potency for inhibiting smooth muscle contraction, and that is still potent at concentrations reaching the lung periphery, may foster airway closure and air trapping, resulting in no net gain or even a decline in lung function.

Ubiquitin ligase signalling networks shape presynaptic development, function and disease.

Ubiquitin ligases are important regulators of nervous system development, function and disease. To date, numerous ubiquitin ligases have been discovered that regulate presynaptic biology. Here, we discuss recent findings on presynaptic ubiquitin ligases that include members from the three major ubiquitin ligase classes: RING, RBR and HECT. Several themes emerge based on findings across a range of model systems. A cadre of ubiquitin ligases is required presynaptically to orchestrate development and transmission at synapses. Multiple ubiquitin ligases deploy both enzymatic and non-enzymatic mechanisms, and act as hubs for signalling networks at the synapse. Both excitatory and inhibitory presynaptic terminals are influenced by ligase activity. Finally, there are several neurodevelopmental disorders and neurodegenerative diseases associated with presynaptic ubiquitin ligases. These findings highlight the growing prominence and biomedical relevance of the presynaptic ubiquitin ligase network.

Calming the Wind: A Traditional Chinese Medicine Practitioner's Approach to Wartime Acute Stress Disorder Symptoms.

In this narrative essay, a traditional Chinese medicine (TCM) practitioner describes the challenge of treating three survivors of a terror attack, all of whom were presenting various symptoms of acute stress disorder (ASD). Working in new and exceptionally demanding circumstances - with thousands of people injured in an extensive and direct terror attack, with relatives taken hostages and entire communities evacuated from their homes - the practitioner looked for an effective treatment strategy to alleviate symptoms of stress response. He found it in the interface between TCM and the function of the autonomic nervous system.

Adaptive Cellular Radiations and the Genetic Mechanisms Underlying Animal Nervous System Diversification.

In animals, the nervous system evolved as the primary interface between multicellular organisms and the environment. As organisms became larger and more complex, the primary functions of the nervous system expanded to include the modulation and coordination of individual responsive cells via paracrine and synaptic functions as well as to monitor and maintain the organism's own internal environment. This was initially accomplished via paracrine signaling and eventually through the assembly of multicell circuits in some lineages. Cells with similar functions and centralized nervous systems have independently arisen in several lineages. We highlight the molecular mechanisms that underlie parallel diversifications of the nervous system.

A dopaminergic basis of behavioral control.

Both goal-directed and automatic processes shape human behavior, but these processes often conflict. Behavioral control is the decision about which process guides behavior. Despite the importance of behavioral control for adaptive decision-making, its neural mechanisms remain unclear. Critically, it is unknown if there are mechanisms for behavioral control that are distinct from those supporting the formation of goal-relevant knowledge. We performed deep phenotyping of individual dopamine system function by combining multiple PET scans, fMRI, and dopaminergic drug administration in a within-subject, double-blind, placebo-controlled design. Subjects performed a rule-based response time task, with goal-directed and automatic decision-making operationalized as model-based and model-free influences on behavior. We found a double dissociation between two aspects of ventral striatal dopamine physiology: D2/3 receptor availability and dopamine synthesis capacity. Convergent and causal evidence indicated that D2/3 receptors regulate behavioral control by enhancing model-based and blunting model-free influences on behavior but do not affect model-based knowledge formation. In contrast, dopamine synthesis capacity was linked to the formation of model-based knowledge but not behavioral control. D2/3 receptors also modulated frontostriatal functional connectivity, suggesting they regulate behavioral control by gating prefrontal inputs to the striatum. These results identify central mechanisms underlying individual and state differences in behavioral control and point to striatal D2/3 receptors as targets for interventions for improving goal-directed behavior.

Groundwaterscapes: A Global Classification and Mapping of Groundwater's Large‐Scale Socioeconomic, Ecological, and Earth System Functions

AbstractGroundwater is a dynamic component of the global water cycle with important social, economic, ecological, and Earth system functions. We present a new global classification and mapping of groundwater systems, which we call groundwaterscapes, that represent predominant configurations of large‐scale groundwater system functions. We identify and map 15 groundwaterscapes which offer a new lens to conceptualize, study, model, and manage groundwater. Groundwaterscapes are derived using a novel application of sequenced self‐organizing maps that capture patterns in groundwater system functions at the grid cell level (∼10 km), including groundwater‐dependent ecosystem type and density, storage capacity, irrigation, safe drinking water access, and national governance. All large aquifer systems of the world are characterized by multiple groundwaterscapes, highlighting the pitfalls of treating these groundwater bodies as lumped systems in global assessments. We evaluate the distribution of Global Groundwater Monitoring Network wells across groundwaterscapes and find that industrial agricultural regions are disproportionately monitored, while several groundwaterscapes have next to no monitoring wells. This disparity undermines the ability to understand system dynamics across the full range of settings that characterize groundwater systems globally. We argue that groundwaterscapes offer a conceptual and spatial tool to guide model development, hypothesis testing, and future data collection initiatives to better understand groundwater's embeddedness within social‐ecological systems at the global scale.

Research Progress on Immunomodulatory Effects of Poly (Lactic-co- Glycolic Acid) Nanoparticles Loaded with Traditional Chinese Medicine Monomers.

Immunomodulatory mechanisms are indispensable and key factors in maintaining the balance of the environment in humans. When the immune function of the immune system is impaired, autoimmune diseases occur. Excessive body fatigue, natural aging of the human body, malnutrition, genetic factors and other reasons cause low immune function, due to which the body is prone to being infected by bacteria or cancer. Clinically, the existing therapeutic drugs still have problems such as high toxicity, long treatment cycle, drug resistance and high price, so we still need to explore and develop a high efficiency and low toxicity drug. Poly(lactic-co-glycolic acid) (PLGA) refers to a nontoxic polymer compound that exhibits excellent biocompatibility. Traditional Chinese medicine (TCM) monomers come from natural plants, and have the characteristics of high efficiency and low toxicity. Applying PLGA to TCM monomers can make up for the defects of traditional dosage forms, improve bioavailability, reduce the frequency and dosage of drug use, and reduce toxicity and side effects, thus having the characteristics of sustained release and targeting. Accordingly, PLGA nanoparticles loaded with TCM monomers have been the focus of development. The previous research on drug loading advantages, preparation methods, and immune regulation of TCM PLGA nanoparticles is summarized in the following sections.