Are micro/nanorobots an effective solution to eliminate micro/nanoplastics in water/wastewater treatment plants?

The extensive production and widespread use of plastic products have resulted in the gradual escalation of plastic pollution. Micro/nano/plastic pollution has become a global issue, and addressing how to "green" remove them is a crucial topic that needs to be tackled at this stage. Recently, micro/nanorobots have offered a promising solution for improving water monitoring and remediation as an environmentally friendly remediation strategy. Micro/nanorobots have been proven to efficiently remove micro/nanoplastics from water bodies. Micro/nanoplastics are captured by micro/nanorobots in water through electrostatic adsorption and electrophoretic interactions, and separation is achieved under the action of an external transverse rotating magnetic field. Their small size enables them to navigate easily in complex environments, while magnetic and optical drives help them move along established routes and reach different areas. With the assistance of these innovative robots, diffusion-limited reactions can be overcome, allowing for active contact with target pollutants. However, research on the removal of micro/nanoplastics by micro/nanorobots is still in its early stages. The dependence on chemical fuels and high costs severely limit the development and application of micro/nanorobots. Micro/nanoplastics are frequently captured by micro/nanorobots, but the degradation efficiency of micro/nanoplastics remains very low. Additionally, the secondary pollution caused by micro/nanorobots is also a key factor limiting their implementation. Although micro/nanorobots are a very promising technology for removing micro/nanoplastics, they still need to be explored in their applications. This paper discusses the opportunities and challenges faced by micro/nanorobots in removing micro/nanoplastics. Development and application of self-driven intelligent micro/nanorobots will help expedite the eco-friendly removal of micro/nanoplastics and other emerging pollutants.

The regulation of glucose and lipid metabolism through the interaction of dietary polyphenols and polysaccharides via the gut microbiota pathway.

The interaction of polyphenols-polysaccharides-gut microbiota to promote health benefits has become a hotspot and direction for precise dietary intervention strategies and foundational research in biomedicine. Both dietary polyphenols and polysaccharides possess biological activities that regulate body health. Single components, due to their inherent structure and physicochemical properties, have a low bioavailability, thus are unable to exert their optimal effects. The compound structure formed by the interaction of polyphenols and polysaccharides can enhance their functional properties, thereby more effectively promoting health benefits and preventing diseases. This review primarily focuses on the roles played by polyphenols and polysaccharides in regulating glucose and lipid metabolism, the improvement of glucose and lipid metabolism through the gut microbial pathway by polyphenols and polysaccharides, and the mechanisms by which polyphenols and polysaccharides interact to regulate glucose and lipid metabolism. A considerable amount of preliminary research has confirmed the regulatory effects of plant polyphenols and polysaccharides on glucose and lipid metabolism. However, studies on the combined effects and mechanisms of these two components are still very limited. This review aims to provide a reference for subsequent research on their interactions and changes in functional properties.

CuNi alloy anchored on dual-substrate TiOx/N-doped carbon nanofibers as a bifunctional electrocatalyst for rechargeable zinc-air batteries.

Development of non-noble metal-based electrocatalysts to enhance the performance of zinc-air batteries (ZABs) is of great significance, but it remains a formidable challenge due to their poor stability and activity. Herein, a bifunctional CuNi-TiOx/NCNFS electrocatalyst, featuring with electron-rich copper-nickel (CuNi) alloy nanoparticles anchored on titanium oxide/N-doped carbon nanofibers (TiOx/NCNFS), is constructed by a dual-substrate loading strategy. The introduction of TiOx has led to a significant increase in the stability of the dual-substrate. The strong electronic interaction between CuNi and TiOx strengthens the anchoring of active metal sites, thus accelerating the electron transfer. Theoretical calculations unclose that NCNFS can regulate the charge distribution of TiOx, inducing the charge transfer from NCNFS â†’ TiOx â†’ CuNi, thereby reducing the d-band center of Cu and Ni, which is beneficial to the desorption of intermediate oxide species of the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). Therefore, CuNi-TiOx/NCNFS delivers a remarkable bifunctional performance with a low OER overpotential of 258 mV at 10 mA cm-2 and an ORR half-wave potential of 0.85  V. When assembled into ZABs, CuNi-TiOx/NCNFS shows a low potential gap of 0.64 V, a higher power density of 149.6 mW cm-2 at 330 mA cm-2, and an outstanding stability for 250 h at 5mA cm-2. This study provides a novel approach by constructing dual-substrate to tune the electronic structure of active metal sites for efficient rechargeable ZABs.

Strategic exploration of whole grain cereals in modulating the glycaemic response.

In the current context, diabetes presents itself as a widespread and complex global health issue. This study explores the significant influence of food microstructure and food matrix components interaction (protein, lipid, polyphenols, etc.) on the starch digestibility and the glycaemic response of post-prandial glycemia, focusing on the potential effectiveness of incorporating bioactive components from whole grain cereals into dietary strategies for the management and potential prevention of diabetes. This study aims to integrate the regulation of postprandial glycaemic homeostasis, including the complexities of starch digestion, the significant potential of bioactive whole grain components and the impact of food processing, to develop a comprehensive framework that combines these elements into a strategic approach to diabetes nutrition. The convergence of these nutritional strategies is analyzed in the context of various prevalent dietary patterns, with the objective of creating an accessible approach to mitigate and prevent diabetes. The objective remains to coalesce these nutritional paradigms into a coherent strategy that not only addresses the current public health crisis but also threads a preventative approach to mitigate future prevalence and impact.

Preparation, structural characterization, and functional properties of wheat gluten amyloid fibrils-chitosan double network hydrogel as delivery carriers for ferulic acid.

It has been demonstrated that ferulic acid (FA) can be effectively encapsulated using wheat gluten amyloid fibrils (AF) and chitosan (CS) in a double network hydrogel (DN) form, with cross-linking mediated by Genipin (GP). Within this system, the DN comprising gluten AF-FA and CS-FA exhibited optimal loading metrics at a formulation designated as DN8, achieving a load efficiency of 88.5 % and a load capacity of 0.78 %. Analysis through fluorescence quenching confirmed that DN8 harbored the highest quantity of FA. Fourier-transform infrared spectroscopy (FTIR) further verified a significant increase in ß-sheet content post-hydrogel formation, enhancing the binding capacity for FA. Rheological assessments indicated a transition from solution to gel, delineating the phase state of the DN. Comprehensive in vitro digestion studies revealed that DN8 provided superior sustained release properties, exhibited the highest total antioxidant capacity, and displayed potent inhibitory activities against angiotensin I converting enzyme (ACE) and acetylcholinesterase (Ach-E). Additionally, the DN significantly bolstered the stability of FA against photothermal degradation. Collectively, these findings lay foundational insights for the advancement of the wheat gluten protein AF-based delivery system for bioactive compounds and provided a theoretical basis for the development of functional foods.

Laser-enzyme dual responsive liposomes to regulate autophagy in synergy with phototherapy for melanoma treatment.

Phototherapy can cause autophagy while killing tumour cells, leading to tumour recurrence and metastasis. Here, we constructed a laser and enzyme dual responsive nanodrug delivery system Tf-Te@CTSL-HCQ (TT@CH) to precisely regulate autophagy in synergy with phototherapy to inhibit the proliferation and metastasis of melanoma. Firstly, transferrin (Tf) was used as a nanoreactor to synthesise phototherapy agent Tf-Te by the biological template mineralisation method. Then, the thermosensitive liposome modified with FAP-α-responsive peptide (CAP) was used as a carrier to encapsulate autophagy inhibitor hydroxychloroquine (HCQ) and Tf-Te, to obtain an intelligent TT@CH delivery system. Once arriving at the tumour site, TT@CH can be cleaved by FAP-α overexpressed on cancer-associated fibroblasts (CAFs), and release Tf-Te and HCQ. Then Tf-Te can target melanoma cells and exert PTT/PDT anti-tumour effect. What's more, hyperpyrexia induced by PTT can further promote drugs release from TT@CH. Meanwhile, HCQ simultaneously inhibited autophagy of CAFs and melanoma cells, and down-regulated IL-6 and HMGB1 secretion, thus effectively inhibiting melanoma metastasis. Pharmacodynamic results exhibited the best anti-tumour effect of TT@CH with the highest tumour inhibition rate of 91.3%. Meanwhile, lung metastatic nodules of TT@CH treated mice reduced by 124.33 compared with that of mice in control group. Overall, TT@CH provided an effective therapy strategy for melanoma.

Multiple infections secondary to immunosuppression after Chlamydia psittaci infection: a case report.

This study presents the clinical profile of a 74-year-old male patient admitted to the hospital due to a 20-day history of coughing, chest tightness, and dyspnea. Upon admission, the patient presented with fever, tachycardia, and tachypnea. Clinical examination revealed evidence of lung infection, sepsis, and multi-organ dysfunction, alongside abnormal blood gas analysis and elevated C-reactive protein (CRP) levels. Pathogen testing confirmed Chlamydia psittaci (C. psittaci), infection. Throughout the treatment course, the patient developed concurrent fungal and viral infections, necessitating a comprehensive approach involving combined antibiotic and antifungal therapy. Despite encountering treatment-related complications, the patient demonstrated clinical improvement with aggressive management. This case underscores the importance of recognizing immune suppression subsequent to Chlamydia infection, emphasizing the critical role of early diagnosis, intervention, and standardized treatment protocols in enhancing patient prognosis.

Advances in relieving exercise fatigue for curcumin: Molecular targets, bioavailability, and potential mechanism.

Intense and prolonged physical activity can lead to a decrease in muscle capacity, making it difficult to maintain the desired exercise intensity and resulting in exercise fatigue. The long-term effects of exercise fatigue can be very damaging to the body, so it is an urgent problem to be addressed. The intervention of foodborne active substances will be an effective measure. There is growing evidence that the molecular structure and function of curcumin have a positive effect on relieving fatigue. In this review, we summarize curcumin's molecular structure, which enables it to bind to a wealth of molecular targets, regulate signaling pathways, and thus alleviate exercise fatigue through a variety of mechanisms, including reducing oxidative stress, inhibiting inflammation, reducing metabolite accumulation, and regulating energy metabolism. The effects of curcumin on fatigue-related markers were analyzed from the perspective of animal models and human models and based on the bidirectional interaction between curcumin and intestinal microbiota: Intestinal microbiota can transform curcumin, and curcumin regulates gut microbiota through metabolic pathways, providing a new perspective for alleviating fatigue. This review contributes to a more comprehensive understanding of the possible molecular mechanisms of curcumin in anti-fatigue and provides a new possibility for the development of functional foods in the future.

Transcription factor GmAlfin09 regulates endoplasmic reticulum stress in soybean via peroxidase GmPRDX6.

Soybean (Glycine max [L.] Merr.) is a valuable oil crop but is also highly susceptible to environmental stress. Thus, developing approaches to enhance soybean stress resistance is vital to soybean yield improvement. In previous studies, transcription factor Alfin has been shown to serve as an epigenetic regulator of plant growth and development. However, no studies on Alfin have yet been reported in soybean. In this study, the endoplasmic reticulum (ER) stress- and reactive oxygen species (ROS)-related GmAlfin09 was identified. Screening of genes co-expressed with GmAlfin09 unexpectedly led to the identification of soybean peroxidase 6 (GmPRDX6). Further analyses revealed that both GmAlfin09 and GmPRDX6 were responsive to ER stress, with GmPRDX6 localizing to the ER under stress. Promoter binding experiments confirmed the ability of GmAlfin09 to bind to the GmPRDX6 promoter directly. When GmAlfin09 and GmPRDX6 were overexpressed in soybean, enhanced ER stress resistance and decreased ROS levels were observed. Together, these findings suggest that GmAlfin09 promotes the upregulation of GmPRDX6, and GmPRDX6 subsequently localizes to the ER, reduces ROS levels, promotes ER homeostasis, and ensures the normal growth of soybean even under ER stress. This study highlights a vital target gene for future molecular breeding of stress-resistant soybean lines.

NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers.

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the biosynthesis of nicotinamide adenine dinucleotide (NAD+), making it a potential target for cancer therapy. Two challenges hinder its translation in the clinic: targeting the extracellular form of NAMPT (eNAMPT) remains insufficient, and side effects are observed in normal tissues. We previously utilized proteolysis-targeting chimera (PROTAC) to develop two compounds capable of simultaneously degrading iNAMPT and eNAMPT. Unfortunately, the pharmacokinetic properties were inadequate, and toxicities similar to those associated with traditional inhibitors arose. We have developed a next-generation PROTAC molecule 632005 to address these challenges, demonstrating exceptional target selectivity and bioavailability, improved in vivo exposure, extended half-life, and reduced clearance rate. When combined with nicotinic acid, 632005 exhibits safety and robust efficacy in treating NAPRT-deficient pan-cancers, including xenograft models with hematologic malignancy and prostate cancer and patient-derived xenograft (PDX) models with liver cancer. Our findings provide clinical references for patient selection and treatment strategies involving NAMPT-targeting PROTACs.

Identification and characterization of two Bacillus anthracis bacteriophages.

Anthrax is an acute infectious zoonotic disease caused by Bacillus anthracis, a bacterium that is considered a potential biological warfare agent. Bacillus bacteriophages shape the composition and evolution of bacterial communities in nature and therefore have important roles in the ecosystem community. B. anthracis phages are not only used in etiological diagnostics but also have promising prospects in clinical therapeutics or for disinfection in anthrax outbreaks. In this study, two temperate B. anthracis phages, vB_BanS_A16R1 (A16R1) and vB_BanS_A16R4 (A16R4), were isolated and showed siphovirus-like morphological characteristics. Genome sequencing showed that the genomes of phages A16R1 and A16R4 are 36,569 bp and 40,059 bp in length, respectively. A16R1 belongs to the genus Wbetavirus, while A16R4 belongs to the genus Hubeivirus and is the first phage of that genus found to lyse B. anthracis. Because these two phages can comparatively specifically lyse B. anthracis, they could be used as alternative diagnostic tools for identification of B. anthracis infections.

Extreme condition-tolerant stretchable flexible supercapacitor and triboelectric nanogenerator based on carrageenan-enhanced gel for energy storage, energy collection and self-powered sensing.

As flexible electronics devices for energy storage, mechanical energy collection and self-powered sensing, stretchable flexible supercapacitor and triboelectric nanogenerator (TENG) have attracted extensive attention. However, it is difficult to satisfy the requirements of high safety and resistance to extreme conditions. Dual roles of mechanical and electrical enhancement of inorganic salt are put forward, and a carrageenan (CG) enhanced poly (N-hydroxyethyl acrylamide)/CG/lithium chloride/glycerol (PCLG) conductive gel is prepared by designing hydrogen bonding self-crosslinking and chain entanglement. A high concentration and rapid deposition strategy is proposed to prepare a PCLG gel-based stretchable flexible all-in-one supercapacitor for energy storage, and a single electrode PCLG gel-based TENG is designed for mechanical energy collection, self-powered strain and tactile sensing. The supercapacitor has high capacitance, excellent cycling stability. The TENG possesses efficient energy harvesting with high and stable output voltage and power density, and sensitive and stable self-powered strain and tactile sensing without external power supply. Even under extreme conditions such as low temperatures, self-healing after damage, prolonged placement, deformation, post-deformation, multiple continuous work, pinprick and burning, the supercapacitor and TENG still have excellent properties. Therefore, we provide novel ideas to design flexible supercapacitor and TENG used under extreme conditions for future wearable electronics.

Metaphire guillelmi exhibited predominant capacity of arsenic efflux.

Earthworm could regulate their body concentration of arsenic via storage or excretion, and the ability of As efflux among different earthworms is not consistent. Here, whole and semi As exposure patterns with 0-10-30-60-100 mg kg-1 exposure concentrations were set to characterize the As efflux in geophagous earthworm, Metaphire guillelmi. Cast As (As-C) and earthworms' antioxidative responses were monitored to explore the efflux mechanisms under 30 mg kg-1 As-spiked soil (As30), besides, As concentration in earthworm tissue after egestion and dissection depurations were compared. In the whole exposure pattern, As concentration in gut content (As-G, 19.2-120.3 mg kg-1) surpassed that in the tissue (As-T, 17.2-53.2 mg kg-1), and they both increased with exposure concentrations. With the prolong time, they firstly increased and kept stable between day 10-15, then As-G increased while As-T decreased between day 15-20. In the semi-exposure pattern, both As-G and As-T decreased when M. guillelmi was transferred to clean soil for 5 days. During the 42-day incubation in As30, the antioxidative responses including reactive oxygen species (ROS), glutathione (GSH) and glutathione-S-transferase (GST) were firstly increased and then decreased, and As-C (13.9-43.9 mg kg-1) kept higher than As-G (14.2-35.1 mg kg-1). Significantly positive correlations were found between As-T and GSH, As-C and GST. Moreover, tissue As after dissection (11.6-22.9 mg kg-1) was obviously lower than that after egestion (11.4-26.4 mg kg-1), but significantly related to ROS and GSH. Taken together, M. guillelmi exhibited excellent capacity of As efflux, and GSH explained tissue As accumulation while GST facilitated the As elimination via cast. Besides, dissection instead of egestion revealed the As efflux in M. guillelmi more accurately. These findings contributed to a better understanding of how geophagous earthworm M. guillelmi regulated tissue As accumulation for As stress tolerance, and recommended an optimal depuration mode to characterize As accumulation.

Evaluating the psychometric properties of the simplified Chinese version of PROMIS-29 version 2.1 in patients with hematologic malignancies.

The Patient-Reported Outcomes Measurement Information System 29-item Profile version 2.1 (PROMIS-29 V2.1) is a widely utilized self-reported instrument for assessing health outcomes from the patients' perspectives. This study aimed to evaluate the psychometric properties of the PROMIS-29 V2.1 Chinese version among patients with hematological malignancy. Conducted as a cross-sectional, this research was approved by the Medical Ethical Committee of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (registration number QTJC2022002-EC-1). We employed convenience sampling to enroll eligible patients with hematological malignancy from four tertiary hospitals in Tianjin, Shandong, Jiangsu, and Anhui province in China between June and August 2023. Participants were asked to complete a socio-demographic information questionnaire, the PROMIS-29 V2.1, and the Functional Assessment of Cancer Therapy-General (FACT-G). We assessed the reliability, ceiling and floor effects, structural, convergent discriminant and criterion validity of the PROMIS-29 V2.1. A total of 354 patients with a mean age of 46.93 years was included in the final analysis. The reliability of the PROMIS-29 V2.1 was affirmed, with Cronbach's α for the domains ranging from 0.787 to 0.968. Except sleep disturbance, the other six domains had ceiling effects, which were seen on physical function (26.0%), anxiety (37.0%), depression (40.4%), fatigue (18.4%), social roles (18.9%) and pain interference (43.2%), respectively. Criterion validity was supported by significant correlations between the PROMIS-29 V2.1 and FACT-G scores, as determined by the Spearman correlation test (P < 0.001). Confirmatory factor analysis (CFA) indicated a good model fit, with indices of χ2/df (2.602), IFI (0.960), and RMSEA (0.067). The Average Variance Extracted (AVE) values for the seven dimensions of PROMIS-29 V2.1, ranging from 0.500 to 0.910, demonstrated satisfactory convergent validity. Discriminant validity was confirmed by ideal √AVE values. The Chinese version of the PROMIS-29 V2.1 profile has been validated as an effective instrument for assessing symptoms and functions in patients with hematological malignancy, underscoring its reliability and applicability in this specific patient group.

Formation and Application of Starch-Polyphenol Complexes: Influencing Factors and Rapid Screening Based on Chemometrics.

Understanding the nuanced interplay between plant polyphenols and starch could have significant implications. For example, it could lead to the development of tailor-made starches for specific applications, from bakinag and brewing to pharmaceuticals and bioplastics. In addition, this knowledge could contribute to the formulation of functional foods with lower glycemic indexes or improved nutrient delivery. Variations in the complexes can be attributed to differences in molecular weight, structure, and even the content of the polyphenols. In addition, the unique structural characteristics of starches, such as amylose/amylopectin ratio and crystalline density, also contribute to the observed effects. Processing conditions and methods will always alter the formation of complexes. As the type of starch/polyphenol can have a significant impact on the formation of the complex, the selection of suitable botanical sources of starch/polyphenols has become a focus. Spectroscopy coupled with chemometrics is a convenient and accurate method for rapidly identifying starches/polyphenols and screening for the desired botanical source. Understanding these relationships is crucial for optimizing starch-based systems in various applications, from food technology to pharmaceutical formulations.

In-Sb Covalent Bonds over Sb2Se3/In2Se3 Heterojunction for Enhanced Photoelectrochemical Water Splitting.

Antimony selenide is a promising P-type photocatalyst, but it has a large number of deep energy level defects, leading to severe carrier recombination. The construction of a heterojunction is a common way to resolve this problem. However, the conventional heterojunction system inevitably introduces interface defects. Herein, we employ in situ synthesis to epitaxially grow In2Se3 nanosheets on Sb2Se3 nanorods and form In-Sb covalent interfacial bonds. This petal-shaped heterostructure reduced interface defects and enhanced the efficiency of carrier separation and transport. In this work, the photocurrent density in the proposed Sb2Se3/In2Se3 photocathode is 0.485 mA cm-2 at 0 VRHE, which is 30 times higher than that of pristine Sb2Se3 and it has prominent long-term stability for 24 h without obvious decay. The results reveal that the synergy of the bidirectional built-in electric field constructed between In2Se3 and Sb2Se3 and the solid In-Sb interfacial bonds together build a high-efficiency transport channel for the photogenerated carriers that display enhanced photoelectrochemical (PEC) water-splitting performance. This work provides efficient guidance for reducing interface defects via the in situ synthesis and construction of interfacial bonds.

In situ autophagy regulation in synergy with phototherapy for breast cancer treatment.

Autophagy is an important factor in reducing the efficacy of tumor phototherapy (including PTT and PDT). Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT. This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy. To achieve this goal, we first synthesized TRANSFERRIN (Tf) biomimetic mineralized nano-tellurium (Tf-Te) as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly. The autophagy inhibitor hydroxychloroquine (HCQ) and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ. After entering breast cancer cells through the "self-guidance system", Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation, to efficiently induce PTT/PDT effect. Meanwhile, the disulfide bond broke down in response to GSH, and the nanoparticles disintegrated to release Fe2+ and HCQ at fixed points. They simultaneously induce lysosomal alkalinization and increased osmotic pressure, effectively inhibit autophagy, and synergistically enhance the therapeutic effect of phototherapy. In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6% on 4T1 tumor-bearing mice. This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

Differentially Expressed Genes Identification of Kohlrabi Seedlings (Brassica oleracea var. caulorapa L.) under Polyethylene Glycol Osmotic Stress and AP2/ERF Transcription Factor Family Analysis.

Osmotic stress is a condition in which plants do not get enough water due to changes in environmental factors. Plant response to osmotic stress is a complex process involving the interaction of different stress-sensitive mechanisms. Differentially expressed genes and response mechanisms of kohlrabi have not been reported under osmotic stress. A total of 196,642 unigenes and 33,040 differentially expressed unigenes were identified in kohlrabi seedlings under polyethylene glycol osmotic stress. AP2/ERF, NAC and eight other transcription factor family members with a high degree of interaction with CAT and SOD antioxidant enzyme activity were identified. Subsequently, 151 AP2/ERF genes were identified and analyzed. Twelve conserved motifs were searched and all AP2/ERF genes were clustered into four groups. A total of 149 AP2/ERF genes were randomly distributed on the chromosome, and relative expression level analysis showed that BocAP2/ERF genes of kohlrabi have obvious specificity in different tissues. This study lays a foundation for explaining the osmotic stress resistance mechanism of kohlrabi and provides a theoretical basis for the functional analysis of BocAP2/ERF transcription factor family members.

STING Agonist cGAMP Attenuates Sleep Deprivation-Induced Neuroinflammation and Cognitive Deficits via TREM2 Up-Regulation.

Sleep deprivation (SD) has been associated with several adverse effects, including cognitive deficit. Emerging evidence suggests microglia-associated neuroinflammation is a potential trigger of cognitive deficit after SD. Stimulator of interferon genes (STING) constitutes an important factor in host immune response to pathogenic organisms and is found in multiple cells, including microglia. STING is involved in neuroinflammation during neuronal degeneration, although how STING signaling affects SD-induced neuroinflammation remains unexplored. In the present study, the chronic sleep restriction (CSR) model was applied to examine the effects of STING signaling on cognition. The results revealed that cGAMP, a high-affinity and selective STING agonist, significantly improved cognitive deficit, alleviated neural injury, and relieved neuroinflammation in CSR mice by activating the STING-TBK1-IRF3 pathway. Moreover, triggering receptor expressed on myeloid cells 2 (TREM2) was upregulated in CSR mice treated with cGAMP, and this effect was abolished by STING knockout. TREM2 upregulation induced by cGAMP regulated the microglia from pro-inflammatory state to anti-inflammatory state, thereby relieving neuroinflammation in CSR mice. These findings indicate cGAMP-induced STING signaling activation alleviates SD-associated neuroinflammation and cognitive deficit by upregulating TREM2, providing a novel approach for the treatment of SD-related nerve injury.