Current advances and future trends of hormesis in disease.

Hormesis, an adaptive response, occurs when exposure to low doses of a stressor potentially induces a stimulatory effect, while higher doses may inhibit it. This phenomenon is widely observed across various organisms and stressors, significantly advancing our understanding and inspiring further exploration of the beneficial effects of toxins at doses both below and beyond traditional thresholds. This has profound implications for promoting biological regulation at the cellular level and enhancing adaptability throughout the biosphere. Therefore, conducting bibliometric analysis in this field is crucial for accurately analyzing and summarizing its current research status. The results of the bibliometric analysis reveal a steady increase in the number of publications in this field over the years. The United States emerges as the leading country in both publication and citation numbers, with the journal Dose-Response publishing the highest number of papers in this area. Calabrese E.J. is a prominent person with significant contributions and influence among authors. Through keyword co-occurrence and trend analysis, current hotspots in this field are identified, primarily focusing on the relationship between hormesis, oxidative stress, and aging. Analysis of highly cited references predicts that future research trends may center around the relationship between hormesis and stress at different doses, as well as exploring the mechanisms and applications of hormesis. In conclusion, this review aims to visually represent hormesis-related research through bibliometric methods, uncovering emerging patterns and areas of focus within the field. It provides a summary of the current research status and forecasts trends in hormesis-related research.

Photo-transformation of isoproturon under UV-A irradiation: The synergy of nitrite and natural organic matter.

Isoproturon (IPU), a widely utilized phenylurea herbicide, is recognized as an emerging contaminant. Previous studies have predominantly attributed the degradation of IPU in natural waters to indirect photolysis by natural organic matter (NOM). Here, we demonstrate that nitrite (NO2-) also serves as an important photosensitizer that induces the photo-degradation of IPU. Through radical quenching tests, we identify hydroxyl radicals (•OH) and nitrogen dioxide radicals (NO2•) originating from NO2- photolysis as key players in IPU degradation, resulting in the generation of a series of hydroxylated and nitrated byproducts. Moreover, we demonstrate a synergistic effect on the photo-transformation of IPU when both NOM and NO2- are present in the reaction mixture. The observed rate constant (kobs) for IPU removal increases to 0.0179 ± 0.0002 min-1 in the co-presence of NO2- (50 µM) and NOM (2.5 mgC/L), surpassing the sum of those in the presence of each alone (0.0135 ± 0.0004 min-1). NOM exhibits multifaceted roles in the indirect photolysis of IPU. It can be excited by UV and transformed to excited triplet states (3NOM*) which oxidize IPU to IPU•+ that undergoes further degradation. Simultaneously, NOM can mitigate the reaction by reducing the IPU•+ intermediate back to the parent IPU. However, the presence of NO2- alters this dynamic, as IPU•+ rapidly couples with NO2•, accelerating IPU degradation and augmenting the formation of mono-nitrated IPU. These findings provide in-depth understandings on the photochemical transformation of environmental contaminants, especially phenylurea herbicides, in natural waters where NOM and NO2- coexist.

Research Hotspots and Frontiers of Alzheimer's Disease and Gut Microbiota: A Knowledge Mapping and Text Mining Analysis.

Gut microbiota has been confirmed to be closely related to Alzheimer's disease (AD). Research on gut microbiota and AD has also increased significantly. This study aimed to conduct a bibliometric and visual analysis of published studies related to gut microbiota and AD. Based on the Web of Science Core Collection SCI-Expanded database, we utilize Excel 2019 and visualization analysis tools VOSviewer, Co-Occurrence13.2 (COOC13.2), Citespace, HistCite, and Bibliometrix (R-Tool of R-Studio) for analysis. A total of 1093 related kinds of literature were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is China, the institution is Zhejiang University, the author is Walter J Lukiw from the USA, and the journal is the Journal of Alzheimer's Disease. Hotspot research areas include the relationship between gut microbiota metabolism and AD, AD treatments related to the gut microbiota, and diseases related to AD and gut microbiota. The future research direction may be T cells, NLRP3 inflammasome, and Porphyromonas gingivalis. Studies on AD and gut microbiota have grown rapidly in recent years. Our research results may provide valuable references for readers and help researchers better find new research directions in the future.

Oxidative stress in the brain-lung crosstalk: cellular and molecular perspectives.

Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the body's ability to counteract their harmful effects, playing a key role in the pathogenesis of brain and lung-related diseases. This review comprehensively examines the intricate mechanisms by which oxidative stress influences cellular and molecular pathways, contributing to neurodegenerative, cardiovascular, and respiratory disorders. Emphasizing the detrimental effects on both brain and lung health, we discuss innovative diagnostic biomarkers, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), and the potential of antioxidant therapies. For these topics, we provide insights into future research directions in the field of oxidative stress treatment, including the development of personalized treatment approaches, the discovery and validation of novel biomarkers, and the development of new drug delivery systems. This review not only provides a new perspective on understanding the role of oxidative stress in brain and lung-related diseases but also offers new insights for future clinical treatments.

Size-Tunable Elasto-Inertial Sorting of Haematococcus pluvialis in the Ultrastretchable Microchannel.

Haematococcus pluvialis is a good source of astaxanthin, which reduces oxidation in the human body, treats inflammation, and slows the growth of breast and skin cancer cells. Since the size of H. pluvialis is often closely related to astaxanthin yield, size-based microalgal separation has far-reaching significance for high-value algae extraction and algal directed evolution. In this work, we report a novel size-tunable elasto-inertial sorting of H. pluvialis in the Ecoflex ultrastretchable microfluidic devices. Ecoflex microfluidic chips can deform and be flexible, bringing flexibility and stretchability to microchannels as well as new possibilities for large-scale modulation of channel geometry. Here, the effects of velocity, channel elongation, and particle size on the elasto-inertial migration of particles are systematically studied. We found that channel elongation has a strong regulating effect on particle focusing. In addition, we verified the continuous regulation of the sorting threshold of microalgal cells by stretching the channel, providing technical support for the extraction and directed evolution of high-yield microalgae.

Knowledge mapping of COVID-19 and autoimmune diseases: a visual and bibliometric analysis.

BACKGROUND: Many studies have shown an association between COVID-19 and autoimmune diseases (ADs). Studies on COVID-19 and ADs have also increased significantly, but there is no bibliometric analysis to summarize the association between COVID-19 and ADs. The purpose of this study was to perform a bibliometric and visual analysis of published studies related to COVID-19 and ADs. METHODS: Based on the Web of Science Core Collection SCI-Expanded database, we utilize Excel 2019 and visualization analysis tools Co-Occurrence13.2 (COOC13.2), VOSviewer, CiteSpace, and HistCite for analysis. RESULTS: A total of 1736 related kinds of papers were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is the USA, the institution is the Harvard Medical School, the author is Yehuda Shoenfeld from Israel, and the journal is Frontiers in Immunology. Research hotspots include immune responses (such as cytokines storm), multisystem ADs (such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis), treatment modalities (such as hydroxychloroquine, rituximab), vaccination and autoimmune mechanisms (such as autoantibodies, molecular mimicry). The future research direction may be the mechanisms and treatment ideas of the association between ADs and COVID-19 (such as NF-κB, hyperinflammation, antiphospholipid antibodies, neutrophil extracellular traps, granulocyte-macrophage colony-stimulating factor), other cross-diseases of COVID-19 and ADs (such as inflammatory bowel disease, chronic mucocutaneous candidiasis, acute respiratory distress syndrome). CONCLUSION: The growth rate of publications regarding ADs and COVID-19 has risen sharply. Our research results can help researchers grasp the current status of ADs and COVID-19 research and find new research directions in the future.

Proteomics-based analysis of the stress response of Bacillus cereus spores under ultrasound and electrolyzed water treatment.

Ultrasound is a green nonthermal technology with promising applications in microbial inactivation. Electrolyzed water has been investigated and found to have a synergistic inactivation effect of ultrasound on spores. This study used a data-independent-acquisition method to analyze the stress response of Bacillus cereus spores following ultrasound combined with electrolyzed water treatment. We identified 197 differentially expressed proteins under ultrasound combined with an electrolyzed water treatment for which the ratio in the metabolic pathway was the highest. Spores downregulated key proteins in energy metabolic and transportation pathways, in particular in phosphotransferase systems and ATP synthase under ultrasound, electrolyzed water, and combined stress. The results of this study revealed that the key proteins in intracellular metabolism decreased after ultrasound treatment, and the expression of small acid-soluble spore protein and cell wall biosynthesis protein increased. Meanwhile, DNA integration, recombination, and inversion protein and small acid-soluble spore protein were upregulated after electrolyzed water treatment. In general, the spores exhibited stress resistance under external stress. The inactivation of spores by further stress was reduced, which we called "cross-protection."

Aprocitentan: A new development of resistant hypertension.

As the blood pressure threshold for commencing antihypertensive treatment diminishes, the cohort suffering from resistant hypertension (RH) correspondingly expands. Notwithstanding the availability of known antihypertensive medications, there exists a conspicuous lacuna in therapeutic options specifically intended for the management of RH. Currently, aprocitentan is the sole endothelin receptor antagonist (ERA) under development for addressing this pressing clinical challenge. Aprocitentan (ACT-132577), deriving its active form as a metabolite of macitentan, demonstrates oral potency as a dual endothelin (ET) receptor antagonist. This compound effectively obstructs the binding of endothelin-1 (ET-1) to both ETA and ETB receptors, exhibiting an inhibitory potency ratio of 1:16. Clinical investigation of aprocitentan has advanced to phase 3 trials, yielding promising preliminary outcomes.

Metabolic reprogramming in the tumor microenvironment: unleashing T cell stemness for enhanced cancer immunotherapy.

T cells play a pivotal role in the immune system by distinguishing between various harmful pathogens and cancerous cells within the human body and initiating an immune response. Within the tumor microenvironment (TME), immune effector T cells encounter both immunosuppressive cells and factors that hinder their functionality. Additionally, they endure robust and persistent antigenic stimulation, often leading to exhaustion and apoptosis. However, the stemness of T cells, characterized by their ability to survive and self-renew over extended periods, represents a primary target in immune checkpoint therapies such as anti-PD-1 therapy. T cell stemness encompasses specific memory T cell subsets and progenitor-exhausted T cells with stem cell-like properties. Therefore, understanding the impact of the TME on T cell stemness, including factors like K+, lactate, and H+, holds significant importance and can facilitate the mitigation of terminal T-cell depletion, the identification of potential resilient biomarkers or therapeutic targets resistant to immune checkpoint therapies, and ultimately lead to sustained anti-tumor effects. Thus, it offers a novel perspective for advancing tumor immunotherapy.

A free-standing, phase-change liquid metal mold for 3D flexible microfluidics.

This paper describes a method to fabricate the 3D microfluidic channel using the free-standing, phase-change gallium mold. Three approaches to prepare the free-standing gallium molds are described. The solid metal framework is strong enough to stand against the gravity. After casting, the embedded gallium molds are melted from solid to liquid and then extracted from the encasing elastomer to form the 3D microfluidic channel due to the phase change property. Since this method is compatible with many encasing materials (e.g., elastomers, gels, resins, ceramics), the encasing materials will bring novel functionalities to the microfluidic chip. Two proof-of-concept experiments have been demonstrated. Firstly, a soft, sticky, on-skin microfluidic cooler is developed based on this method to deliver the focused, minimal invasive cooling power at arbitrary skins of human body with temperature control. Secondly, an ultra-stretchable viscoelastic microchannel with the ultra-soft base is fabricated to continuously tune the viscoelastic particle focusing with a large dynamic range. This proposed technique suggests the new possibilities for the development of lab-on-a-chip applications.

Garden Landscape Design Method in Public Health Urban Planning Based on Big Data Analysis Technology.

Aiming at the goal of high-quality development of the landscape architecture industry, we should actively promote the development and integration of digital, networked, and intelligent technologies and promote the intelligent and diversified development of the landscape architecture industry. Due to the limitation of drawing design technology and construction method, the traditional landscape architecture construction cannot really understand the public demands, and the construction scheme also relies on the experience and subjective aesthetics of professionals, resulting in improper connection between design and construction. At present, under the guidance of the national strategy, under the background of the rapid development of digital technologies such as 5G, big data, cloud computing, Internet of Things, and digital twins, the high integration of landscape architecture construction and digital technology has led to the transformation of the production mode of landscape architecture construction. Abundant professional data and convenient information processing platform enable landscape planners, designers, and builders to evaluate the whole life cycle of the project more scientifically and objectively and realize the digitalization of the whole process of investigation, analysis, design, construction, operation, and maintenance. For the landscape architecture industry, the significance of digital technology is not only to change the production tools but also to update the environmental awareness, design response, and construction methods, which makes the landscape architecture planning and design achieve the organic combination of qualitative and quantitative and also makes the landscape architecture discipline more scientific and rational. In this paper, the new method of combining grey relational degree with machine learning is used to provide new guidance for traditional landscape planning by using big data information in landscape design and has achieved very good results. The article analyzes the guidance of landscape architecture design under the big data in China and provides valuable reference for promoting the construction of landscape architecture in China.

Robust high-resolution direction-of-arrival estimation method using DenseBlock-based U-net.

Direction-of-arrival (DOA) estimation is widely used in underwater detection and localization. To address the high-resolution DOA estimation problem, a DenseBlock-based U-net structure is proposed in this paper. U-net is a U-shaped fully convolutional neural network, which yields a two-dimensional image. DenseBlock is a more efficient structure than typical convolutional layers. The proposed network replaces the concatenated convolutional layers in the original U-net with DenseBlocks. Through training, the network can remove the interference of sidelobes and noise in a conventional beam forming bearing-time record (BTR) and get a clean BTR; hence, this method has narrow beam width and few sidelobes. In addition, the network can be trained by simulation data and applied in actual data when the simulated and actual data are similar in BTR features, so the method has high generalization. For a multi-target problem, the network does not need to be trained on all cases with different target quantities and therefore can reduce the training set size. As a data-driven method, it does not rely on prior assumptions of the array model and possesses better robustness to array imperfections than typical model-based DOA algorithms. Simulations and experiments verify the advantages of the proposed method.

Poly(ADP-ribosylation) of P-TEFb by PARP1 disrupts phase separation to inhibit global transcription after DNA damage.

DNA damage shuts down genome-wide transcription to prevent transcriptional mutagenesis and to initiate repair signalling, but the mechanism to stall elongating RNA polymerase II (Pol II) is not fully understood. Central to the DNA damage response, poly(ADP-ribose) polymerase 1 (PARP1) initiates DNA repair by translocating to the lesions where it catalyses protein poly(ADP-ribosylation). Here we report that PARP1 inhibits Pol II elongation by inactivating the transcription elongation factor P-TEFb, a CDK9-cyclin T1 (CycT1) heterodimer. After sensing damage, the activated PARP1 binds to transcriptionally engaged P-TEFb and modifies CycT1 at multiple positions, including histidine residues that are rarely used as an acceptor site. This prevents CycT1 from undergoing liquid-liquid phase separation that is required for CDK9 to hyperphosphorylate Pol II and to stimulate elongation. Functionally, poly(ADP-ribosylation) of CycT1 promotes DNA repair and cell survival. Thus, the P-TEFb-PARP1 signalling plays a protective role in transcription quality control and genomic stability maintenance after DNA damage.

All-fiber-optic vector magnetic field sensor based on side-polished fiber and magnetic fluid.

A kind of compact all-fiber-optic vector magnetic sensor is proposed and demonstrated. The sensor consists of a side-polished-fiber (SPF)-integrated with singlemode-no core-singlemode (SNS) fiber structure. A section of side-polished fiber breaks the axially symmetry of the composite structure. The as-fabricated sensor supports vector sensing and has a magnetic field strength sensitivity of up to -2370 pm/mT over 2-6 mT range. The physical mechanism is that the modal interference is strongly influenced by the refractive index (RI) near the side-polished surface. The advantages of the proposed sensor lie in low cost, simple structure and easy manufacture, which make it attractive in the field of magnetic field vector sensing.