To explore the mechanism of gypenosides in the treatment of liver injury in rats based on GC-MS metabolomics and bile acid metabolism pathway.

Gynostemma pentaphyllum is a herbaceous vine of Cucurbitaceae family, and its principal pharmacological components, gypenosides (GPs), have been proved to be effective in various liver diseases. However, the mechanisms of GPs on liver injury are still to be studied for further. This investigation utilized the CCl4-induced liver injury rat model (LI) to comprehensively explore the mechanism of action of GPs in the treatment of chemical liver injury by comparing the metabolomic changes in four groups rats. In this study, the therapeutic efficacy of GPs in a liver injury rat model induced by weekly gavage of CCl4 was evaluated by inflammatory factors, oxidative damage indexes, and histopathological sections. Then, GC-MS technology was used to identify the metabolic profile of GPs in treating liver injury. Finally, the content variation of metabolites (BAs and SCFAs) was measured to elucidate the mechanism of GPs in the treatment of CCl4-induced liver injury. After 8 weeks of administration, GPs effectively reduced the degree of LI and appeared a substantial tendency of reversing in the levels of MDA, GSH, CYP7E1, CYP7A1 and CYP27A1. Untargeted metabolomics suggested that GPs may play a role in BAs and SCFAs metabolism. Targeted metabolomics and ELISA confirmed the key role of GPs in increasing SCFAs levels and regulating BAs metabolism. Overall, this study indicated that GPs can alleviate CCl4-induced liver injury. And GPs may exert beneficial effects on LI by affecting their metabolites (SCFAs and BAs).

Rotating cell culture system-induced injectable self-assembled microtissues with epidermal stem cells for full-thickness skin repair.

Epidermal stem cells (EpSCs) are crucial for wound healing and tissue regeneration, and traditional culture methods often lead to their inactivation. It is urgent to increase the yield of high quality EpSCs. In this study, primary EpSCs were isolated and cultured in a serum-free, feeder-free culture system. EpSCs are then expanded in a dynamic 3D environment using a rotating cell culture system (RCCS) with biodegradable porous microcarriers (MC). Over a period of 14 days, the cells self-assembled into microtissues with superior cell proliferation compared to 3D static culture. Immunofluorescence and qPCR analyses consistently showed that the stemness of the 3D microtissues was preserved, especially the COL17A1 associated with anti-aging was highly expressed in RCCS induced microtissues. In vivo experiments demonstrated that the group treated with 3D microtissues loaded with EpSCs showed enhanced early wound healing, and the injectable 3D microtissues were more conducive to maintaining cell viability and differentiation potential. Our study provides valuable insights into the dynamic 3D culture of EpSCs and introduces an injectable therapy using 3D microtissues loaded with EpSCs, which provides a new and effective approach for cell delivery and offering a promising strategy for guiding the regeneration of full-thickness skin defects.

The NAD+ precursor nicotinamide riboside protects against postovulatory aging in vitro.

PURPOSE: Postovulatory aging (POA) of oocytes is clinically significant as it mirrors the degeneration observed in maternally aged oocytes, leading to substantial impairments in oocyte quality and the success rates of artificial reproductive technology (ART). The molecular alterations associated with POA, such as the degeneration of the first polar body, an increase in perivitelline space, reactive oxygen species (ROS) accumulation, energy depletion, and chromosomal and DNA damage, underscore the urgency of finding interventions to mitigate these effects. This study aims to identify whether nicotinamide riboside (NR) can prevent POA during the process of in vitro culture and raise the success rates of ART. METHOD: Taking advantage of an in vitro postovulatory oocyte aging model, we examined the morphological integrity and NAD+ levels of ovulated mouse MII oocytes after 24 h of culturing. Following in vitro fertilization, we assessed the embryonic developmental potential of oocytes affected by POA. Using immunofluorescence and confocal microscopy, we measured the levels of ROS, mitochondrial function, and γH2AX. We also evaluated spindle assembly and chromosome alignment. Additionally, we detected the distribution of cortical granules to assess the metabolic and quality changes in POA oocytes with the supplementation of NR. To further our analysis, quantitative real-time PCR was conducted to measure the mRNA expression levels of antioxidant enzymes Sod1 and Gpx1 in the oocytes. RESULTS: With 200 µM NR supplementation during in vitro culture for 24 h, the oocytes from POA demonstrated reduced signs of aging-related decline in oocyte quality, including reduced ROS accumulation, improved mitochondrial function, and corrected mis-localization of cortical granules. This improvement in oocyte quality is likely due to the inhibition of oxidative stress via the NAD+/SIRT1 signaling pathway, which also helped to restore normal spindle assembly and chromosome alignment, as well as reduce the elevated levels of γH2AX, thereby potentially enhancing the embryonic development potential. CONCLUSION: Current research provides evidence that NR is an efficient and safe natural component that prevents the process of POA and is thus a potential ideal antiaging drug for raising the success rates of ART in clinical practice.

Relaxed Stability Criteria for Delayed Memristor-Based Neural Network Systems via a Novel Matrix-Separation Legendre Inequality.

This article studies the issue of stability in memristor-based neural network (MNN) systems with time-varying delays. First, a novel matrix-separation Legendre inequality is proposed to achieve a tight hierarchical bound on augmented-type integral terms. To derive implementable inequality conditions, several delay-dependent matrices are introduced to eliminate the reciprocal terms associated with time-varying delay. Furthermore, a new Lyapunov-Krasovskii (L-K) functional is proposed by incorporating augmented-type double integrals and delay-product terms. A series of free-weighting matrices are introduced into the L-K functional, leveraging the zero-sum equations and the S-procedure pertaining to both the delay and its derivative. Based on the proposed matrix-separation Legendre inequality and L-K functional, the derived stability conditions exhibit reduced conservatism, as validated by three numerical cases and simulation results.

Enhanced outdoor visual localization using Py-Net voting segmentation approach.

Camera relocalization determines the position and orientation of a camera in a 3D space. Althouh methods based on scene coordinate regression yield highly accurate results in indoor scenes, they exhibit poor performance in outdoor scenarios due to their large scale and increased complexity. A visual localization method, Py-Net, is therefore proposed herein. Py-Net is based on voting segmentation and comprises a main encoder containing Py-layer and two branch decoders. The Py-layer comprises pyramid convolution and 1 × 1 convolution kernels for feature extraction across multiple levels, with fewer parameters to enhance the model's ability to extract scene information. Coordinate attention was added at the end of the encoder for feature correction, which improved the model robustness to interference. To prevent the feature loss caused by repetitive structures and low-texture images in the scene, deep over-parameterized convolution modules were incorporated into the seg and vote decoders. Landmark segmentation and voting maps were used to establish the relation between images and landmarks in 3D space, reducing anomalies and achieving high precision with a small number of landmarks. The experimental results show that, in multiple outdoor scenes, Py-Net achieves lower distance and angle errors compared to existing methods. Additionally, compared to VS-Net, which also uses a voting segmentation structure, Py-Net reduces the number of parameters by 31.85% and decreases the model size from 236MB to 170 MB.

Efficient, High-Quality Engineering of Therapeutic Extracellular Vesicles on an Integrated Nanoplatform.

Engineered extracellular vesicles (EVs) have been recognized as important therapeutics for gene and cell therapy. To achieve clinically desired therapy, technologies for EV engineering have high demands on the efficacy in producing EVs and their qualities, which, however, remain challenging to conventional routes due to their limited control on therapeutic payload delivery, EV secretion, and extracellular microenvironments. Here, we report a nanoplatform (denoted as PURE) that enables efficient electro-transfection while stimulating cells to produce high-quality EVs carrying functional RNAs. PURE further employs an ammonium removal zone to maintain the physiological conditions of the extracellular microenvironment and an EV uptake zone that efficiently (87.1%) captures EVs in situ with porous hydrogels. The platform achieved about a 12-fold higher yield of engineered EVs and a 146-fold abundance of desired therapeutics compared to those naturally secreted from cells. The PURE-engineered miR-130a-EVs were validated for effectively upregulating the mTOR signaling pathway in both in vitro and in vivo. Their therapeutic capability was then verified by enhancing the in vitro activation of primordial follicles. In vivo applications further highlighted the therapeutic effects of miR-130a-EVs in restoring ovary function in aged mice. The PURE platform represents a strategy for the clinical translation of EV-mediated therapy.

Hypoxia-induced mitochondrial fission regulates the fate of bone marrow mesenchymal stem cells by maintaining HIF1α stabilization.

For mesenchymal stem cells derived from bone marrow, a controlled reduction in ambient oxygen concentration has been recognized as a facilitator of osteogenic differentiation and the formation of calcium nodules. However, the specific molecular mechanisms underlying this phenotype remain unclear. The aim of this study was to elucidate the impact of hypoxia on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and to explore the involvement of mitophagy and the regulation of mitochondrial dynamics mediated by the mitochondrial dynamic regulatory factor FUN14 domain-containing 1 (FUNDC1). Our findings suggest that FUNDC1 is required for promoting osteogenic differentiation in BMSCs under hypoxic conditions. However, this effect was not dependent on FUNDC1-mediated mitophagy but rather on FUNDC1-mediated regulation of mitochondrial fission. At the mechanistic level, FUNDC1 binds more DNM1L and less OPA1 under hypoxic conditions, leading to an upsurge in mitochondrial division. This heightened mitochondrial division culminates in the increased translocation of Parkin to mitochondria, diminishing its interactions with HIF1α in the cytoplasm and consequently facilitating HIF1α deubiquitination and stabilization. In summary, FUNDC1-regulated mitochondrial division in hypoxic culture emerges as a critical determinant for the translocation of Parkin to mitochondria, ultimately maintaining HIF1α stabilization and promoting osteogenic differentiation.

Particle formation in response to different protein formulations and containers: Insights from machine learning analysis of particle images.

Subvisible particle count is a biotherapeutics stability indicator widely used by pharmaceutical industries. A variety of stresses that biotherapeutics are exposed to during development can impact particle morphology. By classifying particle morphological differences, stresses that have been applied to monoclonal antibodies (mAbs) can be identified. This study aims to evaluate common biotherapeutic drug storage and shipment conditions that are known to impact protein aggregation. Two different studies were conducted to capture particle images using micro-flow imaging and to classify particles using a convolutional neural network. The first study evaluated particles produced in response to agitation, heat, and freeze-thaw stresses in one mAb formulated in five different formulations. The second study evaluated particles from two common drug containers, a high-density polyethylene bottle and a glass vial, in six mAbs exposed solely to agitation stress. An extension of this study was also conducted to evaluate the impact of sequential stress exposure compared to exposure to one stress alone, on particle morphology. Overall, the convolutional neural network was able to classify particles belonging to a particular formulation or container. These studies indicate that storage and shipping stresses can impact particle morphology according to formulation composition and mAb.

The Different Concentrations of Applied Exogenous Sugars Widely Influence the Specificity, Significance and Physiological Relevance of Study Outcomings.

Plant growth and development are governed via signal networks that connect inputs from nutrient status, hormone signals, and environmental cues. Substantial researches have indicated a pivotal role of sugars as signalling molecules in plants that integrate external environmental cues and other nutrients with intrinsic developmental programmes regulated via multiple plant hormones. Therefore, plant growth and development are controlled through complication signalling networks. However, in many studies, to obtain more obviously experimental findings, excess concentrations of applied exogenous sugars have aggravated the complexity of this signalling networks. Once researchers underestimate this complexity, a series of contradictory or contrasting findings will be generated. More importantly, in terms of these contradictory findings, more contradictory study outcomings are derived. In this review, we carefully analyze some reports, and find that these reports have confused or neglected that the sugar-antagonism of ethylene signalling is specific or conditional. As a result, many contradictory conclusions are generated, which will in turn misdirect the scientific community.

Protective Role of (-)-Epicatechin on Trimethylamine-N-Oxide (TMAO)-Induced Cardiac Hypertrophy via SP1/SIRT1/SUMO1 Signaling Pathway.

(-)-Epicatechin (EPI) is beneficial for cardiovascular health. Trimethylamine N-oxide (TMAO), a gut microbe-derived food metabolite, is strongly associated with the risk of cardiovascular diseases. However, the effects and underlying mechanisms of EPI on TMAO-induced cardiac hypertrophy remain unclear. This study aimed to determine whether EPI inhibits TMAO-induced cardiac hypertrophy. Plasma levels of TMAO in control participants and patients with cardiac hypertrophy were measured and analyzed. Male C57BL/6 mice were randomly divided into control group, TMAO group, EPI group and TMAO + EPI group. According to the groups assignments, mice received intraperitoneal (i.p.) injection of normal saline or i.p. injection of TMAO (150 mg/kg/day) for 14 days. The EPI group was given intragastric (i.g.) administration of EPI alone (1 mg/kg/day) for 21 days, and TMAO + EPI group received i.g. administration of EPI for 7 days before starting i.p. injection of TMAO, continuing until the end of the TMAO treatment. Histological analyses of the mice's hearts was accessed by H&E and Masson staining. In vitro, H9c2 cells were induced to hypertrophy by TMAO (10 µM) for 24 h and were pre-treated with or without EPI (10 µM) for 1 h. Protein level of cardiac hypertrophy markers and Sp1/SIRT1/SUMO1 pathway were determined by western blot. The plasma level of TMAO was 2.66 ± 1.59 µmol/L in patients with cardiac hypertrophy and 0.62 ± 0.30 µmol/L in control participants. EPI attenuated TMAO-induced hypertrophy in H9c2 cells. In vivo, TMAO induced cardiac hypertrophy and impaired the cardiac function of mice. Pathological staining showed that TMAO induced cardiac hypertrophy and collagen deposition in mice. EPI treatment improved the cardiac function, inhibited the myocardial hypertrophy induced by TMAO. EPI significantly attenuated the TMAO-induced upregulation of ANP and BNP and the downregulation of SP1, SIRT1 and SUMO1 in vivo and in vitro. EPI may suppress TMAO-induced cardiac hypertrophy by activating the Sp1/SIRT1/SUMO1 signaling pathway.

Psychedelics and Consciousness: Expanding the Horizons of Mind and Therapy.

Psychedelics have long been recognized not only for their profound impact on human consciousness but also for their potential therapeutic applications. This perspective explores the multifaceted relationship between psychedelics and consciousness, emphasizing their capacity to alter sensory perceptions, disrupt self-referential thought processes, and catalyze profound spiritual and existential experiences. As research advances, psychedelics are being integrated into therapeutic settings, challenging existing psychiatric models and offering new insights into the complex nature of consciousness and mental health. This emerging paradigm marks the need for careful regulation and ethical considerations in the therapeutic use of psychedelics, promising a more holistic approach to mental health disorders.

An efficient CRISPR-Cas12a-mediated MicroRNA knockout strategy in plants.

In recent years, the CRISPR-Cas9 nuclease has been used to knock out MicroRNA (miRNA) genes in plants, greatly promoting the study of miRNA function. However, due to its propensity for generating small insertions and deletions, Cas9 is not well-suited for achieving a complete knockout of miRNA genes. By contrast, CRISPR-Cas12a nuclease generates larger deletions, which could significantly disrupt the secondary structure of pre-miRNA and prevent the production of mature miRNAs. Through the case study of OsMIR390 in rice, we confirmed that Cas12a is a more efficient tool than Cas9 in generating knockout mutants of a miRNA gene. To further demonstrate CRISPR-Cas12a-mediated knockout of miRNA genes in rice, we targeted nine OsMIRNA genes that have different spaciotemporal expression and have not been previously investigated via genetic knockout approaches. With CRISPR-Cas12a, up to 100% genome editing efficiency was observed at these miRNA loci. The resulting larger deletions suggest Cas12a robustly generated null alleles of miRNA genes. Transcriptome profiling of the miRNA mutants, as well as phenotypic analysis of the rice grains revealed the function of these miRNAs in controlling gene expression and regulating grain quality and seed development. This study established CRISPR-Cas12a as an efficient tool for genetic knockout of miRNA genes in plants.

SLAMF8 regulates osteogenesis and adipogenesis of bone marrow mesenchymal stem cells via S100A6/Wnt/ß-catenin signaling pathway.

BACKGROUND: The inflammatory microenvironment plays an essential role in bone healing after fracture. The signaling lymphocytic activation molecule family (SLAMF) members deeply participate in inflammatory response and make a vast difference. METHODS: We identified SLAMF8 in GEO datasets (GSE129165 and GSE176086) and co-expression analyses were performed to define the relationships between SLAMF8 and osteogenesis relative genes (RUNX2 and COL1A1). In vitro, we established SLAMF8 knockdown and overexpression mouse bone marrow mesenchymal stem cells (mBMSCs) lines. qPCR, Western blot, ALP staining, ARS staining, Oil Red O staining and Immunofluorescence analyses were performed to investigate the effect of SLAMF8 in mBMSCs osteogenesis and adipogenesis. In vivo, mice femoral fracture model was performed to explore the function of SLAMF8. RESULTS: SLAMF8 knockdown significantly suppressed the expression of osteogenesis relative genes (RUNX2, SP7 and COL1A1), ALP activity and mineral deposition, but increased the expression of adipogenesis relative genes (PPARγ and C/EBPα). Additionally, SLAMF8 overexpression had the opposite effects. The role SLAMF8 played in mBMSCs osteogenic and adipogenic differentiation were through S100A6 and Wnt/ß-Catenin signaling pathway. Moreover, SLAMF8 overexpression mBMSCs promoted the healing of femoral fracture. CONCLUSIONS: SLAMF8 promotes osteogenesis and inhibits adipogenesis of mBMSCs via S100A6 and Wnt/ß-Catenin signaling pathway. SLAMF8 overexpression mBMSCs effectively accelerate the healing of femoral fracture in mice.

miRNA375-3p/rapamycin mediates the mTOR pathway by decreasing PS1, enhances microglial cell activity to regulate autophagy in Alzheimer's disease.

The clinical prevention, diagnosis, treatment, and drug development of Alzheimer's disease (AD) require urgent detection of novel targets and methods. Autophagy and microglia are significantly associated with the pathogenesis of early AD. This study indicated that microRNA-375-3p can inhibit autophagy by promoting mTOR phosphorylation in normal physiological conditions, while microRNA-375-3p promoted autophagy and enhanced neural repair by inhibiting the expression of presenilin 1 in early AD pathogenesis. Furthermore, co-treatment of rapamycin, and microRNA-375-3p can synergistically promote the autophagy and microglial activation in a neuroprotective manner, clear Aß accumulation, repair nerve damage, and alleviate cognitive dysfunction and memory defects in APP/PS1 TG mice. This research revealed the impact and mechanism of miR375-3p on the early stage of AD through in vivo and in vitro experiments and provides new ideas and directions for the early treatment of AD.

Thermal Ablation of Pulmonary Nodules by Electromagnetic Navigation Bronchoscopy Combined With Real-Time CT-Based 3D Fusion Navigation:Report of One Case.

A nodule in the right middle lobe of the lung was treated by a combination of cone-beam CT,three-dimensional registration for fusion imaging,and electromagnetic navigation bronchoscopy-guided thermal ablation.The procedure lasted for 90 min,with no significant bleeding observed under the bronchoscope.The total radiation dose during the operation was 384 mGy.The patient recovered well postoperatively,with only a small amount of blood in the sputum and no pneumothorax or other complications.A follow-up chest CT on the first day post operation showed that the ablation area completely covered the lesion,and the patient was discharged successfully.

Dimethylsulfoniopropionate (DMSP) Increases Longevity and Mitochondrial Function in Caenorhabditis elegans: Implications for the Role of the Global Sulfur Cycle in Terrestrial Ecosystems.

Dimethylsulfoniopropionate (DMSP) is a compound synthesized by marine phytoplankton that contributes to the oceanic sulfur cycle. Interestingly, DMSP has also been found in algal species and several terrestrial plants, forming part of the global sulfur cycle. However, compared to its role in the marine environment, the impact of DMSP on terrestrial ecosystems remains relatively unexplored. In this study, DMSP was shown to promote longevity and prevent age-associated functional decline in Caenorhabditis elegans (C. elegans), a soil-dwelling organism. DMSP decreased mitochondrial content and improved mitochondrial function in C. elegans at the old stage, which was via enhancing autophagy flux. It was demonstrated that DMSP significantly increased the expression of autophagy and mitophagy genes during aging. Furthermore, DMSP protected against Parkinson's disease (PD) induced by α-synuclein (α-syn) aggregation via autophagy. Mechanistic studies showed that DMSP directly activated nuclear translocation of the Skinhead-1 (SKN-1) transcription factor from the cytoplasm. Moreover, SKN-1 was involved in DMSP-induced autophagy and played a key role in lifespan extension and α-syn clearance in C. elegans. In conclusion, DMSP delays physiological aspects of aging in C. elegans, providing insights into the interplay between the global sulfur cycle and terrestrial organisms.

Association of serum lipidomic profiles with risk of intracranial aneurysm: A Mendelian randomization study.

A two-sample Mendelian randomization (MR) analysis was utilized to assess the causal relationship between lipidomic profiles and the risk of intracranial aneurysms (IAs). Genetic variants related to lipidomic profiles (227 components) and IA [IA, aneurysmal subarachnoid hemorrhage (aSAH) only, unruptured IA (uIA) only] were obtained from published genome-wide association studies (GWASs) or the IEU Open GWAS project and used as instrumental variables for MR analysis. The inverse-variance weighted method was used in the primary analyses to derive causality estimates and was expressed as odds ratio (OR) with 95% confidence interval (CI). Of these 227 lipidomic profiles, only genetically predicted high levels of cholesterol to total lipids ratio in very small very-low-density lipoproteins (VLDL) [OR = 0.629 (95% CI, 0.504-0.786)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.637 (95% CI, 0.509-0.797)], ratio of docosahexaenoic acid to total fatty acids [OR = 0.691 (95% CI, 0.582-0.820)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.630 (95% CI, 0.522-0.760)] reduced the risk of aSAH, whereas genetically predicted high ratio of monounsaturated fatty acids to total fatty acids [OR = 1.471 (95% CI, 1.215-1.781)] increased the risk of aSAH. Moreover, genetically predicted high levels of cholesterol to total lipids ratio in very small VLDL [OR = 0.657 (95% CI, 0.542-0.798)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.663 (95% CI, 0.548-0.803)], free cholesterol to total lipids ratio in small VLDL [OR = 0.682 (95% CI, 0.560-0.832)], phospholipids to total lipids ratio in small VLDL [OR = 0.674 (95% CI, 0.548-0.830)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.678 (95% CI, 0.569-0.808)] reduced the risk of IA. The results of multivariable MR demonstrated that these causal associations persisted after adjusting for systolic blood pressure and cigarettes smoked per day. The effect of serum lipids on IA and aSAH may be mainly caused by subclasses of lipids such as VLDL.

Vapor Nucleation on Hybrid-Wetting Nanoconvex Surfaces: The Competition between Intrinsic Wettability and Topography.

Hybrid-wetting surfaces with hydrophilic spots reduced from the micrometer to nanometer scale have been confirmed to enhance vapor nucleation while simultaneously minimizing droplet pinning. Given that surface topography also plays a critical role in influencing nucleation characteristics, the effect of competition between intrinsic wettability and topography on nucleation remains unclear when both surface topography and hydrophilic regions approach the critical nucleation size. This work investigated vapor nucleation on two types of hybrid-wetting nanoconvex surfaces. On random hybrid-wetting convex surfaces, the most negative potential energy sites were located at the sides of the convex structures, leading vapor to preferentially nucleate at these locations, consistent with observations on homogeneous surfaces. Despite similar average potential energy values across the surface, wettability variations in hydrophilic and hydrophobic atoms significantly alter the surface energy distribution. As the wettability difference between hydrophilic and hydrophobic atoms increases, stronger hydrophilic atoms generate relatively higher local energy regions, promoting vapor rapid nucleation. The edge effect still exists at a hydrophilic atom ratio of 10%, and competition among hydrophilic spots impedes vapor nucleation and growth. However, when the ratio increases to 40%, the increased surface average potential energy promotes the probability of vapor contacting the surface, leading to rapid vapor nucleation on the sides of the convex structures. In addition, surface potential energy analysis and the Monte Carlo method revealed that nucleation locations on nanoconvex surfaces are governed by the competition between intrinsic wettability and topography. When the magnitude of the potential energy generated by the hydrophilic atoms exceeds that from the topography, stronger solid-liquid interactions at the top of the convex structure increase the likelihood of vapor contacting the surface, resulting in nucleation at the top. Conversely, when the magnitude of the potential energy generated by hydrophilic atoms is lower than that from topography, nucleation preferentially still occurs on the sides.

Plant essential oils combined with organic acids restored lipopolysaccharide-induced leaky intestine via gut microbial modulation in weaned piglets.

Intestine derived lipopolysaccharide (LPS) is closely related to systemic inflammation and disorders, yet little is known about its roles in the weanling stress of piglets and its potential as a nutritional intervention target. This study aimed to investigate the potential of essential oils (EO) and organic acids (OA) in mitigating weaning stress in piglets by modulating the circulation of intestine derived LPS. Seventy-two weaned piglets at 21 d old with body weight of 8.12 ± 0.168 kg were randomly divided into a control group (CON) and an experimental group, each consisting of six pens with six piglets per pen, and were fed either a basal diet or a basal diet supplemented with 3 kg/t OA + 500 g/t EO (EO + OA). On the 14th day of the feeding trial, 12 weaned piglets were randomly selected from the CON group, and 6 piglets were selected from the experimental group. Based on diet composition and stress treatment, these 18 piglets were divided into the following three groups: 1) CON group. Piglets were fed a basal diet and received an intraperitoneal injection of saline as a control. 2) LPS group. Piglets were fed a basal diet and received an intraperitoneal injection of LPS (100 µg/kg body weight) to induce stress. 3) EO + OA + LPS group. Piglets were fed a basal diet supplemented with EO and OA and received an intraperitoneal injection of LPS (100 µg/kg body weight) to induce stress. The results showed that EO + OA significantly ameliorated the oxidative imbalance and inflammation disorder induced by LPS in piglets' serum and intestine by inhibiting the activation of the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, compared to the LPS group, supplementation with EO + OA restored LPS-induced reductions in Bcl-2 protein expression in the piglets' intestines (P < 0.05) and mitigated morphological damage; it also enhanced both the protein expression and relative gene expression of the tight junction proteins occludin and claudin-1 (P < 0.05), and reduced the plasma diamine oxidase activity (DAO) and LPS content (P < 0.05). Compared to the CON group, supplementation with EO + OA altered the composition of the intestinal microbiota, increasing beneficial bacteria relative abundance (Faecalibacterium) (P < 0.05) and decreasing harmful bacteria relative abundance [Rikenellaceae_RC9_gut_group (P < 0.01), Negativibacillus (P < 0.05)]. Further analysis revealed that plasma LPS content in piglets was negatively correlated with the relative abundance of Faecalibacterium (r = -0.662, P = 0.021), Akkermansia (r = -0.492, P = 0.031), and average daily gain (ADG) (r = -0.912, P = 0.041). Plasma LPS content was also positively correlated with the plasma inflammatory factors interleukin (IL)-1ß (r = 0.591, P = 0.021), IL-6 (r = 0.623, P = 0.021), IL-12 (r = 561, P = 0.031) contents, and the relative abundance of Negativibacillus (r = 0.712, P = 0.041). In summary, the addition of EO + OA prevents the leakage of intestine derived LPS into the circulation by improving intestinal integrity and microbiota composition, thereby enhancing antioxidant and anti-inflammatory abilities and growth performance of weaned piglets.

Homogenizing Energy Landscape for Efficient and Spectrally Stable Blue Perovskite Light-Emitting Diodes.

Blue perovskite light-emitting diodes (PeLEDs) have attracted enormous attention; however, their unsatisfactory device efficiency and spectral stability still remain great challenges. Unfavorable low-dimensional phase distribution and defects with deeper energy levels usually cause energy disorder, substantially limiting the device's performance. Here, an additive-interface optimization strategy is reported to tackle these issues, thus realizing efficient and spectrally stable blue PeLEDs. A new type of additive-formamidinium tetrafluorosuccinate (FATFSA) is introduced into the quasi-2D mixed halide perovskite accompanied by interface engineering, which effectively impedes the formation of undesired low-dimensional phases with various bandgaps throughout the entire film, thereby boosting energy transfer process for accelerating radiative recombination; this strategy also diminishes the halide vacancies especially chloride-related defects with deep energy level, thus reducing nonradiative energy loss for efficient radiative recombination. Benefitting from homogenized energy landscape throughout the entire perovskite emitting layer, PeLEDs with spectrally-stable blue emission (478 nm) and champion external quantum efficiency (EQE) of 21.9% are realized, which represents a record value among this type of PeLEDs in the pure blue region.