Mesenchymal stromal cells ameliorate mitochondrial dysfunction in α cells and hyperglucagonemia in type 2 diabetes via SIRT1/FoxO3a signaling.

Dysregulation of α cells results in hyperglycemia and hyperglucagonemia in type 2 diabetes mellitus (T2DM). Mesenchymal stromal cell (MSC)-based therapy increases oxygen consumption of islets and enhances insulin secretion. However, the underlying mechanism for the protective role of MSCs in α-cell mitochondrial dysfunction remains unclear. Here, human umbilical cord MSCs (hucMSCs) were used to treat 2 kinds of T2DM mice and αTC1-6 cells to explore the role of hucMSCs in improving α-cell mitochondrial dysfunction and hyperglucagonemia. Plasma and supernatant glucagon were detected by enzyme-linked immunosorbent assay (ELISA). Mitochondrial function of α cells was assessed by the Seahorse Analyzer. To investigate the underlying mechanisms, Sirtuin 1 (SIRT1), Forkhead box O3a (FoxO3a), glucose transporter type1 (GLUT1), and glucokinase (GCK) were assessed by Western blotting analysis. In vivo, hucMSC infusion improved glucose and insulin tolerance, as well as hyperglycemia and hyperglucagonemia in T2DM mice. Meanwhile, hucMSC intervention rescued the islet structure and decreased α- to ß-cell ratio. Glucagon secretion from αTC1-6 cells was consistently inhibited by hucMSCs in vitro. Meanwhile, hucMSC treatment activated intracellular SIRT1/FoxO3a signaling, promoted glucose uptake and activation, alleviated mitochondrial dysfunction, and enhanced ATP production. However, transfection of SIRT1 small interfering RNA (siRNA) or the application of SIRT1 inhibitor EX-527 weakened the therapeutic effects of hucMSCs on mitochondrial function and glucagon secretion. Our observations indicate that hucMSCs mitigate mitochondrial dysfunction and glucagon hypersecretion of α cells in T2DM via SIRT1/FoxO3a signaling, which provides novel evidence demonstrating the potential for hucMSCs in treating T2DM.

Highly Stable Amorphous (Pyro)phosphate Aggregates: Pyrophosphate as a Carrier for Bioactive Ions and Drugs in Bone Repair Applications.

Pyrophosphate is widely used as an iron supplement because of its excellent complexation and hydrolysis ability; however, there are few reports on the use of pyrophosphate in active ionophores for bone repair. In this research, we proposed a simple and efficient ultrasonic method to prepare magnesium-calcium (pyro)phosphate aggregates (AMCPs). Due to strong hydration, AMCPs maintain a stable amorphous form even at high temperatures (400 °C). By changing the molar ratio of calcium and magnesium ions, the content of calcium and magnesium ions can be customized. AMCPs had surface negativity and complexing ability that realized the controlled release of ions (Ca2+, Mg2+, and P) and drugs (such as doxorubicin) over a long period. Pyrophosphate gave it an excellent bacteriostatic effect. Increasingly released Mg2+ exhibited improved bioactivity though the content of Ca2+ decreased. While Mg2+ content was regulated to 15 wt %, it performed significantly enhanced stimulation on the proliferation, attachment, and differentiation (ALP activity, calcium nodules, and the related gene expression of osteogenesis) of mouse embryo osteoblast precursor cells (MC3T3-E1). Furthermore, the high content of Mg2+ also effectively promoted the proliferation, attachment, and migration of human umbilical vein endothelial cells (HUVECs) and the expression of angiogenic genes. In conclusion, pyrophosphate was an excellent carrier for bioactive ions, and the AMCPs we prepared had a variety of active functions for multiscenario bone repair applications.

Advances in the Application of AI Robots in Critical Care: Scoping Review.

BACKGROUND: In recent epochs, the field of critical medicine has experienced significant advancements due to the integration of artificial intelligence (AI). Specifically, AI robots have evolved from theoretical concepts to being actively implemented in clinical trials and applications. The intensive care unit (ICU), known for its reliance on a vast amount of medical information, presents a promising avenue for the deployment of robotic AI, anticipated to bring substantial improvements to patient care. OBJECTIVE: This review aims to comprehensively summarize the current state of AI robots in the field of critical care by searching for previous studies, developments, and applications of AI robots related to ICU wards. In addition, it seeks to address the ethical challenges arising from their use, including concerns related to safety, patient privacy, responsibility delineation, and cost-benefit analysis. METHODS: Following the scoping review framework proposed by Arksey and O'Malley and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a scoping review to delineate the breadth of research in this field of AI robots in ICU and reported the findings. The literature search was carried out on May 1, 2023, across 3 databases: PubMed, Embase, and the IEEE Xplore Digital Library. Eligible publications were initially screened based on their titles and abstracts. Publications that passed the preliminary screening underwent a comprehensive review. Various research characteristics were extracted, summarized, and analyzed from the final publications. RESULTS: Of the 5908 publications screened, 77 (1.3%) underwent a full review. These studies collectively spanned 21 ICU robotics projects, encompassing their system development and testing, clinical trials, and approval processes. Upon an expert-reviewed classification framework, these were categorized into 5 main types: therapeutic assistance robots, nursing assistance robots, rehabilitation assistance robots, telepresence robots, and logistics and disinfection robots. Most of these are already widely deployed and commercialized in ICUs, although a select few remain under testing. All robotic systems and tools are engineered to deliver more personalized, convenient, and intelligent medical services to patients in the ICU, concurrently aiming to reduce the substantial workload on ICU medical staff and promote therapeutic and care procedures. This review further explored the prevailing challenges, particularly focusing on ethical and safety concerns, proposing viable solutions or methodologies, and illustrating the prospective capabilities and potential of AI-driven robotic technologies in the ICU environment. Ultimately, we foresee a pivotal role for robots in a future scenario of a fully automated continuum from admission to discharge within the ICU. CONCLUSIONS: This review highlights the potential of AI robots to transform ICU care by improving patient treatment, support, and rehabilitation processes. However, it also recognizes the ethical complexities and operational challenges that come with their implementation, offering possible solutions for future development and optimization.

Microencapsulation of fish oil by spray drying, spray freeze-drying, freeze-drying, and microwave freeze-drying: Microcapsule characterization and storage stability.

The objective of this paper was to evaluate the effect of spray drying (SD), spray freeze-drying (SFD), freeze-drying (FD), and microwave freeze-drying (MFD) on the characteristics of fish oil (FO) microcapsules. The physicochemical properties, morphology, fatty acid composition, and stability of the microcapsules were analyzed. The encapsulation efficiencies of microcapsules dried by SD, SFD, FD, and MFD were 86.98%, 77.79%, 63.29%, and 57.89%, respectively. SD microcapsules exhibited superior properties in terms of effective loading capacity, color, and flowability. Conversely, SFD microcapsules demonstrated improved solubility. Microencapsulation positively affected the thermal stability of FO, but the content of unsaturated fatty acids decreased. The findings from the storage experiment indicated that the oxidative stability of SD fish oil microcapsules was marginally lower compared to microcapsules produced through three alternative drying techniques, all of which were based on the FD concept. The comparison of various drying methods and their effects on the quality of FO microcapsules offers valuable insights that can serve as a foundation for the industrial production of high-quality microcapsules.

A circular single-stranded DNA mycovirus infects plants and confers broad-spectrum fungal resistance.

Circular single-stranded DNA (ssDNA) viruses have been rarely found in fungi, and the evolutionary and ecological relationships among ssDNA viruses infecting fungi and other organisms remain unclear. In this study, a novel circular ssDNA virus, tentatively named Diaporthe sojae circular DNA virus 1 (DsCDV1), was identified in the phytopathogenic fungus Diaporthe sojae isolated from pear trees. DsCDV1 has a monopartite genome (3185 nt in size) encapsidated in isometric virions (21-26 nm in diameter). The genome comprises seven putative open reading frames encoding a discrete replicase (Rep) split by an intergenic region, a putative capsid protein (CP), several proteins of unknown function (P1-P4), and a long intergenic region. Notably, the two split parts of DsCDV1 Rep share high identities with the Reps of Geminiviridae and Genomoviridae, respectively, indicating an evolutionary linkage with both families. Phylogenetic analysis based on Rep or CP sequences placed DsCDV1 in a unique cluster, supporting the establishment of a new family, tentatively named Gegemycoviridae, intermediate to both families. DsCDV1 significantly attenuates fungal growth and nearly erases fungal virulence when transfected into the host fungus. Remarkably, DsCDV1 can systematically infect tobacco and pear seedlings, providing broad-spectrum resistance to fungal diseases. Subcellular localization analysis revealed that DsCDV1 P3 is systematically localized in the plasmodesmata, while its expression in trans-complementation experiments could restore systematic infection of a movement-deficient plant virus, suggesting that P3 is a movement protein. DsCDV1 exhibits unique molecular and biological traits not observed in other ssDNA viruses, serving as a link between fungal and plant ssDNA viruses and presenting an evolutionary connection between ssDNA viruses and fungi. These findings contribute to expanding our understanding of ssDNA virus diversity and evolution, offering potential biocontrol applications for managing crucial plant diseases.

Cell-free Protein Synthesis System for Building Synthetic Cells.

The Cell-Free Protein Synthesis (CFPS) system has been widely employed to facilitate the bottom-up assembly of synthetic cells. It serves as the host for the core machinery of the Central Dogma, standing as an optimal chassis for the integration and assembly of diverse artificial cellular mimicry systems. Despite its frequent use in the fabrication of synthetic cells, establishing a tailored and robust CFPS system for a specific application remains a nontrivial challenge. In this methods paper, we present a comprehensive protocol for the CFPS system, routinely employed in constructing synthetic cells. This protocol encompasses key stages in the preparation of the CFPS system, including the cell extract, template preparation, and routine expression optimization utilizing a fluorescent reporter protein. Additionally, we show representative results by encapsulating the CFPS system within various micro-compartments, such as monolayer droplets, double-emulsion vesicles, and chambers situated atop supported lipid bilayers. Finally, we elucidate the critical steps and conditions necessary for the successful assembly of these CFPS systems in distinct environments. We expect that our approach will facilitate the establishment of good working practices among various laboratories within the continuously expanding synthetic cell community, thereby accelerating progress in the field of synthetic cell development.

Physicochemical Effect on Coal Pores of Hydrocarbon Chain Length and Mixing of Viscoelastic Surfactants in Clean Fracturing Fluids.

Clean fracturing fluids are environmentally friendly and could have broad applications in permeability enhancement of coal seams. The hydrophobic chain length of the viscoelastic surfactant (VES) and the mixing of VESs with different ionic types have marked effects on the performance of clean fracturing fluids. This paper analyzes the effects of the hydrocarbon chain length of VES and mixing of VESs with different ion types on the pores of coal and discusses the mechanisms controlling the pore changes from a physical and chemical perspective. We found that the coal samples treated with clean fracturing fluid B had the largest porosity change. Adding two methylene groups to the hydrocarbon chain of the cationic VES will increase clay swelling in coal treated with fracturing fluids. Adding 0.1 wt % cocoamidopropyl betaine (zwitterionic VES) to cationic VES fracturing fluids can reduce the extent of clay expansion induced by fracturing fluids. VES with a long hydrocarbon chain has a strong ability to remove kaolinite in hard coal, and the addition of zwitterion VES increases the ability of a clean fracturing fluid to remove kaolinite. These results provide theoretical guidance for the synthesis of new VES molecules and the design of new fracturing fluid formulations.

2D Free-Standing GeS1-xSex with Composition-Tunable Bandgap for Tailored Polarimetric Optoelectronics.

Germanium-based monochalcogenides (i.e., GeS and GeSe) with desirable properties are promising candidates for the development of next-generation optoelectronic devices. However, they are still stuck with challenges, such as relatively fixed electronic band structure, unconfigurable optoelectronic characteristics, and difficulty in achieving free-standing growth. Herein, it is demonstrated that two-dimensional (2D) free-standing GeS1-xSex (0 ≤ x ≤ 1) nanoplates can be grown by low-pressure rapid physical vapor deposition (LPRPVD), fulfilling a continuously composition-tunable optical bandgap and electronic band structure. By leveraging the synergistic effect of composition-dependent modulation and free-standing growth, GeS1-xSex-based optoelectronic devices exhibit significantly configurable hole mobility from 6.22 × 10-4 to 1.24 cm2V-1s⁻1 and tunable responsivity from 8.6 to 311 A W-1 (635 nm), as x varies from 0 to 1. Furthermore, the polarimetric sensitivity can be tailored from 4.3 (GeS0.29Se0.71) to 1.8 (GeSe) benefiting from alloy engineering. Finally, the tailored imaging capability is also demonstrated to show the application potential of GeS1-xSex alloy nanoplates. This work broadens the functionality of conventional binary materials and motivates the development of tailored polarimetric optoelectronic devices.

Activation of the Photosensitive Potential of 2D GaSe by Interfacial Engineering.

Two-dimensional (2D) gallium selenide (GaSe) holds great promise for pioneering advancements in photodetection due to its exceptional electronic and optoelectronic properties. However, in conventional photodetectors, 2D GaSe only functions as a photosensitive layer, failing to fully exploit its inherent photosensitive potential. Herein, we propose an ultrasensitive photodetector based on out-of-plane 2D GaSe/MoSe2 heterostructure. Through interfacial engineering, 2D GaSe serves not only as the photosensitive layer but also as the photoconductive gain and passivation layer, introducing a photogating effect and extending the lifetime of photocarriers. Capitalizing on these features, the device exhibits exceptional photodetection performance, including a responsivity of 28 800 A/W, specific detectivity of 7.1 × 1014 Jones, light on/off ratio of 1.2 × 106, and rise/fall time of 112.4/426.8 µs. Moreover, high-resolution imaging under various wavelengths is successfully demonstrated using this device. Additionally, we showcase the generality of this device design by activating the photosensitive potential of 2D GaSe with other transition metal dichalcogenides (TMDCs) such as WSe2, WS2, and MoS2. This work provides inspiration for future development in high-performance photodetectors, shining a spotlight on the potential of 2D GaSe and its heterostructure.

How Does Physical Activity Enhance the Subjective Well-Being of University Students? A Chain Mediation of Cognitive Reappraisal and Resilience.

BACKGROUND: Regular physical activity is an effective means to enhance university students' subjective well-being. However, current research needs to understand how physical activity enhances the subjective well-being of Chinese university students. Therefore, the study investigated the mechanism of physical activity's impact on university students' subjective well-being and the mediating roles of cognitive reappraisal and resilience in this mechanism. METHODS: The physical activity scale, subjective well-being scale, cognitive reappraisal scale and resilience scale were used to investigate 1350 university students, and the relationship between physical activity, cognitive reappraisal, resilience and university students' subjective well-being was verified through correlation analysis, regression analysis and a Bootstrap method. RESULTS: (1) There is a significant positive correlation between physical activity, cognitive reappraisal, resilience and university students' subjective well-being (p < 0.01); (2) physical activity, cognitive reappraisal and resilience all have a significant positive effects on university students' subjective well-being (p < 0.01); (3) cognitive reappraisal and resilience have significant mediating roles in the process of physical activity affecting university students' well-being, with mediating-effect values of 0.052 and 0.285; (4) the chain-mediating role of cognitive reappraisal and resilience in the process of physical activity affecting university students' well-being is significant, with the chain-mediating effect value of 0.062. CONCLUSION: Promoting university students' participation in physical activity not only directly enhances university students' subjective well-being but also indirectly improves university students' subjective well-being through cognitive reappraisal and resilience.

Induced Mesenchymal Stem Cells-Small Extracellular Vesicles Alleviate Post-stroke Cognitive Impairment by Rejuvenating Senescence of Neural Stem Cells.

Ischemic stroke is typified by hypoxia and a cascade of pathophysiological events, including metabolic dysfunction, ionic dysregulation, excitotoxicity, inflammatory infiltration, and oxidative stress. These ultimately result in neuronal apoptosis or necrosis with constrained neuroregenerative capabilities. In this study, neural stem cells (NSCs) under conditions of oxygen-glucose deprivation (OGD) in vitro and following middle cerebral artery occlusion (MCAO) in vivo were explored. Transcriptome sequencing revealed a decline in NSC differentiation and neurogenesis after OGD exposure, which was related to cellular senescence. This observation was corroborated by increased senescence markers in the MCAO mouse model, reduction in NSC numbers, and decline in neurogenesis. Importantly, iMSC-sEVs (induced mesenchymal stem cells-small extracellular vesicles) have the therapeutic potential to alleviate NSC senescence and rejuvenate their regenerative capacities both in vitro and in vivo. Moreover, iMSC-sEVs contribute to the recovery of cognitive function and synapse loss caused by MCAO.

The roles of templates consisting of amino acids in the synthesis and application of gold nanoclusters.

Gold nanoclusters (AuNCs) with low toxicity, high photostability, and facile synthesis have attracted great attention. The ligand is of great significance in stabilizing AuNCs and regulating their properties. Ligands consisting of amino acids (proteins and peptides) are an ideal template for synthesizing applicative AuNCs due to their inherent bioactivity, biocompatibility, and accessibility. In this review, we summarize the correlation of the template consisting of amino acids with the properties of AuNCs by analyzing different peptide sequences. The selection of amino acids can regulate the fluorescence excitation/emission and intensity, size, cell uptake, and light absorption. By analyzing the role played by AuNCs stabilized by proteins and peptides in the application, universal rules and detailed performances of sensors, antibacterial agents, therapeutic reagents, and light absorbers are reviewed. This review can guide the template design and application of AuNCs when selecting proteins and peptides as ligands.

Polarization-Sensitive Self-Powered Schottky Photodetector with High Photovoltaic Performance Induced by Geometry-Asymmetric Contacts.

Polarization-sensitive photodetectors have attracted considerable attention owing to their potential application prospects in navigation, optical switching, and communication. However, it remains challenging to develop a facile and effective strategy to simultaneously meet the demands of low power consumption, high performance, and excellent polarization sensitivity. Herein, a series of low-symmetry two-dimensional (2D) ReSe2 Schottky photodetectors with geometry-asymmetric contacts are constructed. These devices exhibit excellent photoelectrical performance and impressive polarization sensitivity in the self-powered mode owing to the difference in the Schottky barrier height induced by the asymmetric contact areas, interfacial states, and thickness difference. Particularly, an outstanding responsivity of 379 mA/W, a decent specific detectivity of 6.8 × 1011 Jones, and a high light on/off ratio (Ilight/Idark) of over 105 under 635 nm light illumination are achieved. Scanning photocurrent mapping (SPCM) measurements further confirm that the ReSe2/drain overlapped region (corresponding to the smaller contact area side) with a higher Schottky barrier height plays a dominant role in the generation of photocurrent. Furthermore, the proposed device displays impressive polarization ratios (PRs) of 3.1 and 3.6 at zero bias under 635 and 808 nm irradiation, respectively. The high-resolution single-pixel imaging capability is also demonstrated. This work reveals the great potential of the ReSe2 Schottky photodetector with geometry-asymmetric contacts for high-performance, self-powered, and polarization-sensitive photodetection.

Ideal Photodetector Based on WS2/CuInP2S6 Heterostructure by Combining Band Engineering and Ferroelectric Modulation.

Two-dimensional van der Waals (2D vdW) heterostructure photodetectors have garnered significant attention for their potential applications in next-generation optoelectronic systems. However, current 2D vdW photodetectors inevitably encounter compromises between responsivity, detectivity, and response time due to the absence of multilevel regulation for free and photoexcited carriers, thereby restricting their widespread applications. To address this challenge, we propose an efficient 2D WS2/CuInP2S6 vdW heterostructure photodetector by combining band engineering and ferroelectric modulation. In this device, the asymmetric conduction and valence band offsets effectively block the majority carriers (free electrons), while photoexcited holes are efficiently tunneled and rapidly collected by the bottom electrode. Additionally, the ferroelectric CuInP2S6 layer generates polarization states that reconfigure the built-in electric field, reducing dark current and facilitating the separation of photocarriers. Moreover, photoelectrons are trapped during long-distance lateral transport, resulting in a high photoconductivity gain. Consequently, the device achieves an impressive responsivity of 88 A W-1, an outstanding specific detectivity of 3.4 × 1013 Jones, and a fast response time of 37.6/371.3 µs. Moreover, the capability of high-resolution imaging under various wavelengths and fast optical communication has been successfully demonstrated using this device, highlighting its promising application prospects in future optoelectronic systems.

Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models.

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.

Synchronously Polishing the Lead-Rich Surface and Passivating Surface Defects of CsPb(Br/I)3 Quantum Dots for High-Performance Pure-Red PeLEDs.

Mixed-halide CsPb(Br/I)3 perovskite quantum dots (QDs) are regarded as one of the most promising candidates for pure-red perovskite light-emitting diodes (PeLEDs) due to their precise spectral tuning property. However, the lead-rich surface of these QDs usually results in halide ion migration and nonradiative recombination loss, which remains a great challenge for high-performance PeLEDs. To solve the above issues, we employ a chelating agent of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid hydrate (DOTA) to polish the lead-rich surface of the QDs and meanwhile introduce a new ligand of 2,3-dimercaptosuccinic acid (DMSA) to passivate surface defects of the QDs. This synchronous post-treatment strategy results in high-quality CsPb(Br/I)3 QDs with suppressed halide ion migration and an improved photoluminescence quantum yield, which enables us to fabricate spectrally stable pure-red PeLEDs with a peak external quantum efficiency of 23.2%, representing one of the best performance pure-red PeLEDs based on mixed-halide CsPb(Br/I)3 QDs reported to date.

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis.

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

A transcriptomics-based investigation of the mechanism of pulmonary fibrosis induced by nickel oxide nanoparticles.

Nickel oxide nanoparticles (NiONPs) are an emerging nanomaterial, which poses a huge threat to the health of workplace population. Nanoparticles induce pulmonary fibrosis, and its mechanisms are associated with noncoding RNAs (ncRNAs). However, ncRNAs and competing endogenous RNA (ceRNA) networks which involved in NiONP-induced pulmonary fibrosis are still unclear. This study aimed to identify ncRNA-related ceRNA networks and investigate the role of the Wnt/ß-catenin pathway in pulmonary fibrosis. Male Wistar rats were intratracheally instilled with 0.015, 0.06, and 0.24 mg/kg NiONPs twice a week for 9 weeks. First, we found there were 93 circularRNAs (circRNAs), 74 microRNAs (miRNAs), 124 long non-coding RNAs (lncRNAs), and 1675 messenger RNAs (mRNAs) differentially expressed through microarray analysis. Second, we constructed ceRNA networks among lncRNAs/circRNAs, miRNAs and mRNAs and identified two ceRNA networks (lncMelttl16/miR-382-5p/Hsd17b7 and circIqch/miR-181d-5p/Stat1) after real time-quantitative polymerase chain reaction (RT-qPCR) validation. Furthermore, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, ncRNAs were found to be involved in biological processes and signaling pathways related to pulmonary fibrosis. KEGG analysis showed that NiONPs activated the Wnt/ß-catenin pathway in rats. In vitro, HFL1 cells were treated with 0, 50, 100, and 200 µg/mL NiONPs for 24 h. We found that NiONPs induced collagen deposition and Wnt/ß-catenin pathway activation. Moreover, a blockade of Wnt/ß-catenin pathway alleviated NiONP-induced collagen deposition. In conclusion, these observations suggested that ncRNAs were crucial in pulmonary fibrosis development and that the Wnt/ß-catenin pathway mediated the deposition of collagen.

Didymin protects pancreatic beta cells by enhancing mitochondrial function in high-fat diet-induced impaired glucose tolerance.

PURPOSE: Prolonged exposure to plasma free fatty acids (FFAs) leads to impaired glucose tolerance (IGT) which can progress to type 2 diabetes (T2D) in the absence of timely and effective interventions. High-fat diet (HFD) leads to chronic inflammation and oxidative stress, impairing pancreatic beta cell (PBC) function. While Didymin, a flavonoid glycoside derived from citrus fruits, has beneficial effects on inflammation dysfunction, its specific role in HFD-induced IGT remains yet to be elucidated. Hence, this study aims to investigate the protective effects of Didymin on PBCs. METHODS: HFD-induced IGT mice and INS-1 cells were used to explore the effect and mechanism of Didymin in alleviating IGT. Serum glucose and insulin levels were measured during the glucose tolerance and insulin tolerance tests to evaluate PBC function and insulin resistance. Next, RNA-seq analysis was performed to identify the pathways potentially influenced by Didymin in PBCs. Furthermore, we validated the effects of Didymin both in vitro and in vivo. Mitochondrial electron transport inhibitor (Rotenone) was used to further confirm that Didymin exerts its ameliorative effect by enhancing mitochondria function. RESULTS: Didymin reduces postprandial glycemia and enhances 30-minute postprandial insulin levels in IGT mice. Moreover, Didymin was found to enhance mitochondria biogenesis and function, regulate insulin secretion, and alleviate inflammation and apoptosis. However, these effects were abrogated with the treatment of Rotenone, indicating that Didymin exerts its ameliorative effect by enhancing mitochondria function. CONCLUSIONS: Didymin exhibits therapeutic potential in the treatment of HFD-induced IGT. This beneficial effect is attributed to the amelioration of PBC dysfunction through improved mitochondrial function.

Uncovering Novel QTLs and Candidate Genes for Salt Tolerance at the Bud Burst Stage in Rice through Genome-Wide Association Study.

Salt stress is one of the most important factors limiting rice growth and yield increase. Salt tolerance of rice at the bud burst (STB) stage determines whether germinated seeds can grow normally under salt stress, which is very important for direct seeding. However, reports on quantitative trait loci (QTLs) and candidate genes for STB in rice are very limited. In this study, a natural population of 130 indica and 81 japonica rice accessions was used to identify STB-related QTLs and candidate genes using a genome-wide association study (GWAS). Nine QTLs, including five for relative shoot length (RSL), two for relative root length (RRL), and two for relative root number (RRN), were identified. Five of these STB-related QTLs are located at the same site as the characterized salt tolerance genes, such as OsMDH1, OsSRFP1, and OsCDPK7. However, an important QTL related to RSL, qRSL1-2, has not been previously identified and was detected on chromosome 1. The candidate region for qRSL1-2 was identified by linkage disequilibrium analysis, 18 genes were found to have altered expression levels under salt stress through the RNA-seq database, and 10 of them were found to be highly expressed in the shoot. It was also found that, eight candidate genes (LOC_Os01g62980, LOC_Os01g63190, LOC_Os01g63230, LOC_Os01g63280, LOC_Os01g63400, LOC_Os01g63460, and LOC_Os01g63580) for qRSL1-2 carry different haplotypes between indica and japonica rice, which exactly corresponds to the significant difference in RSL values between indica and japonica rice in this study. Most of the accessions with elite haplotypes were indica rice, which had higher RSL values. These genes with indica-japonica specific haplotypes were identified as candidate genes. Rice accessions with elite haplotypes could be used as important resources for direct seeding. This study also provides new insights into the genetic mechanism of STB.