Oral Supplementation of L-Carnosine Attenuates Acute-Stress-Induced Corticosterone Release and Mitigates Anxiety in CD157 Knockout Mice.

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. A dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders, such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

The significance of CD16+ monocytes in the occurrence and development of chronic thromboembolic pulmonary hypertension: insights from single-cell RNA sequencing.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious pulmonary vascular disease characterized by residual thrombi in the pulmonary arteries and distal pulmonary microvascular remodeling. The pathogenesis of CTEPH remains unclear, but many factors such as inflammation, immunity, coagulation and angiogenesis may be involved. Monocytes are important immune cells that can differentiate into macrophages and dendritic cells and play an important role in thrombus formation. However, the distribution, gene expression profile and differentiation trajectory of monocyte subsets in CTEPH patients have not been systematically studied. This study aims to reveal the characteristics and functions of monocytes in CTEPH patients using single-cell sequencing technology, and to provide new insights for the diagnosis and treatment of CTEPH. Methods: Single-cell RNA sequencing (scRNA-seq) were performed to analyze the transcriptomic features of peripheral blood mononuclear cells (PBMCs) from healthy controls, CTEPH patients and the tissues from CTEPH patients after the pulmonary endarterectomy (PEA). We established a CTEPH rat model with chronic pulmonary embolism caused by repeated injection of autologous thrombi through a central venous catheter, and used flow cytometry to detect the proportion changes of monocyte subsets in CTEPH patients and CTEPH rat model. We also observed the infiltration degree of macrophage subsets in thrombus tissue and their differentiation relationship with peripheral blood monocyte subsets by immunofluorescence staining. Results: The results showed that the monocyte subsets in peripheral blood of CTEPH patients changed significantly, especially the proportion of CD16+ monocyte subset increased. This monocyte subset had unique functional features at the transcriptomic level, involving processes such as cell adhesion, T cell activation, coagulation response and platelet activation, which may play an important role in pulmonary artery thrombus formation and pulmonary artery intimal remodeling. In addition, we also found that the macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients showed pro-inflammatory and lipid metabolism reprogramming features, which may be related to the persistence and insolubility of pulmonary artery thrombi and the development of pulmonary hypertension. Finally, we also observed that CD16+ monocyte subset in peripheral blood of CTEPH patients may be recruited to pulmonary artery intimal tissue and differentiate into macrophage subset with high expression of IL-1ß, participating in disease progression. Conclusion: CD16+ monocytes subset had significant gene expression changes in CTEPH patients, related to platelet activation, coagulation response and inflammatory response. And we also found that these cells could migrate to the thrombus and differentiate into macrophages with high expression of IL-1ß involved in CTEPH disease progression. We believe that CD16+ monocytes are important participants in CTEPH and potential therapeutic targets.

Cinnamaldehyde protects SH-SY5Y cells against advanced glycation end-products induced ectopic cell cycle re-entry.

Accumulation of advanced glycation end-products (AGEs) in the brain contributes significantly to cognitive impairment in patients with diabetes by disrupting the post-mitotic state of neuronal cells, thereby triggering ectopic cell cycle re-entry (CCR) and subsequent neuronal apoptosis. Cinnamaldehyde (CINA), a potential mitigator of cognitive impairment due to its blood glucose-lowering properties, warrants exploration for its role in counteracting diabetes-related neurological damage. In this study, we examined the neuroprotective effect of CINA on AGE-damaged SH-SY5Y human neuroblastoma cells differentiated in vitro. We investigated the impact of CINA on AGE-induced neuronal CCR and apoptosis, finding that it substantially suppressed aberrant DNA replication, precluded cells from entering the mitotic preparatory phase, and diminished apoptosis. Additionally, CINA inhibited the expression of eIF4E without altering S6K1 phosphorylation. These findings indicate that CINA safeguards neuronal cells from AGE-related damage by preventing abnormal CCR, preserving the post-mitotic state of neuronal cells, and reducing AGE-induced apoptosis, potentially through the inhibition of eIF4E-controlled cell proliferation. Our results highlight the prospective utility of CINA in managing diabetic neuropathy.

Controllable Microparticle Spinning via Light without Spin Angular Momentum.

The spin angular momentum (SAM) of an elliptically or circularly polarized light beam can be transferred to matter to drive a spinning motion. It is counterintuitive to find that a light beam without SAM can also cause the spinning of microparticles. Here, we demonstrate controllable spinning of birefringent microparticles via a tightly focused radially polarized vortex beam that has no SAM prior to focusing. To this end, the orbital Hall effect is proposed to control the radial separation of two spin components in the focused field, and tunable transfer of local SAM to microparticles is achieved by manipulating the twisted wavefront of the source light. Our work broadens the perspectives for controllable exertion of optical torques via the spin-orbit interactions.

Application of Ulva lactuca polysaccharide in the preservation of refrigerated of Lateolabrax maculatus fillets.

This study aimed to explore the use of Ulva lactuca polysaccharide (ULP) as a preservative for perch (Lateolabrax maculatus) fillets stored under refrigeration at 4 °C. Fresh perch fillets were treated with ULP (7-10 kDa) and potassium sorbate, respectively, to evaluate their effectiveness in inhibiting bacterial growth and maintain freshness. A 0.5% ULP solution significantly decreased the pH value, total volatile basic nitrogen value, thiobarbituric acid value, and total bacterial count of perch fillets. ULP solution delayed the changes in whiteness and texture of fillets, as well as protein degradation. The acute toxicity experiment further evaluates the safety and reliability of ULP. Simultaneously, utilizing 16S rRNA techniques, the ULP solution inhibited microorganisms known for their strong spoilage capabilities, such as Pseudomonas, Actinetobacter, and Shewanella. Microorganisms with a weaker ability to cause corruption became the dominant bacteria, such as Acetobacter, Lactobacillus, and Faecalibacterium, thereby exerting a degree of inhibition against spoilage.

Haplotype-resolved chromosome-level genome assembly of Huyou (Citrus changshanensis).

Huyou (Citrus changshanensis) is a significant citrus species that originated in Zhejiang Province, China, where it is also primarily cultivated. It is valued for its distinctive flavor and notable health benefits, owing to its high content of bioactive compounds like naringin and limonin. However, the absence of a high quality reference genome has limited the exploration of these health-promoting compounds in Huyou and hindered research into the mechanisms behind its medicinal properties. In this study, we present a phased chromosome-level genome assembly of Huyou. By combining PacBio and Hi-C sequencing, we generated a primary genome assembly and two haplotypes, comprising nine pseudo-chromosomes, with sizes of 339.91 Mb, 323.51 Mb, and 311.89 Mb, respectively. By integrating transcriptome data and annotations of homologous species, we identified a total of 29,775 protein-coding genes in the genome of Huyou. Additionally, we detected lots of structural variants between the two haplotypes. This represents the first reference genome of Huyou, providing a valuable resource for future studies on its agricultural characteristics and medicinal applications.

Comparison of postoperative outcomes between endoscopy assisted minimal invasive direct anterior approach and bikini direct anterior approach in total hip arthroplasty.

BACKGROUND: We have innovatively developed a modified bikini direct anterior approach total hip arthroplasty (THA), endoscopy assisted minimal invasive direct anterior approach (Endo-DAA). The study compared aesthetic appearance of the scar, postoperative radiographic and functional outcomes, and complications of Endo-DAA with Bikini-DAA. METHODS: Patients who underwent primary THA using Endo-DAA or Bikini-DAA were included. The main innovation of Endo-DAA is the use of minimally invasive 5-7 cm proximal transverse incision and distal puncture with an endoscopy assisted split-type tool to complete the acetabular preparation and prosthesis implantation. Outcomes evaluated included evaluation of scar satisfaction, hip reconstruction including inclination, anteversion and leg-length discrepancy (LLD) and patient-reported outcomes including Harris Hip Scores (HHS) and Forgotten Joint Score (FJS). Follow-up time points included preoperative, 6 weeks, 6 months and 12 months. RESULTS: Finally, 195 hips in Endo-DAA and 207 hips in Bikini DAA completed the follow-up. The Endo-DAA group was superior to the Bikini-DAA group in the cosmetic aspects of scars. the cup anteversion angle of Endo-DAA group was significantly better than that in the Bikini-DAA group. The early HHS and FJS of the Endo-DAA group were superior to those of the Bikini-group. Operation time, blood loss, incision length, length of stay and duration to start no-assistive-device walking were also significantly better in the Endo-DAA group. Furthermore, the Bikini-DAA group had a higher incidence of complication. CONCLUSION: Compared with Bikini-incision, Endo-DAA improves patients' subjective satisfaction with scar aesthetics, accelerates rapid recovery of postoperative function, and reduces postoperative complications.

Mogroside Alleviates Diabetes Mellitus and Modulates Intestinal Microflora in Type 2 Diabetic Mice.

Mogroside, the main component of Siraitia grosvenorii (Swingle) C. Jeffrey (Cucurbitaceae) is a natural product with hypoglycemic and intestinal microbiota regulating properties. However, whether the alteration of intestinal microbiota is associated with the antidiabetic effect of mogroside remains poorly understood. This study investigated the mechanism underlying the hypoglycemic effect of mogroside in regulating intestinal flora and attenuating metabolic endotoxemia. Kunming mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet and intraperitoneal injection of streptozotocin were randomly divided into model, pioglitazone (2.57 mg/kg) and mogroside (200, 100, and 50 mg/kg) groups. After 28 d of administration, molecular changes related to glucose metabolism and metabolic endotoxemia in mice were evaluated. The levels of insulin receptor substrate-1 (IRS-1), cluster of differentiation 14 (CD14) and toll-like receptor 4 (TLR4) mRNAs were measured, and the composition of intestinal microflora was determined by 16s ribosomal DNA (rDNA) sequencing. The results showed that mogroside treatment significantly improved hepatic glucose metabolism in T2DM mice. More importantly, mogroside treatment considerably reduced plasma endotoxin (inhibition rate 65.93%, high-dose group) and inflammatory factor levels, with a concomitant decrease in CD14 and TLR4 mRNA levels. Moreover, mogroside treatment reduced the relative abundance of Firmicutes and Proteobacteria (the inhibition rate of Proteobacteria was 85.17% in the low-dose group) and increased the relative abundance of Bacteroidetes (growth rate up to 40.57%, high-dose group) in the intestines of diabetic mice. This study reveals that mogroside can relieve T2DM, regulating intestinal flora and improving intestinal mucosal barrier, indicating that mogroside can be a potential therapeutic agent or intestinal microbiota regulator in the treatment of T2DM.

Panax notoginseng saponins prevent dementia and oxidative stress in brains of SAMP8 mice by enhancing mitophagy.

BACKGROUND: Mitochondrial dysfunction is one of the distinctive features of neurons in patients with Alzheimer's disease (AD). Intraneuronal autophagosomes selectively phagocytose and degrade the damaged mitochondria, mitigating neuronal damage in AD. Panax notoginseng saponins (PNS) can effectively reduce oxidative stress and mitochondrial damage in the brain of animals with AD, but their exact mechanism of action is unknown. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice with age-related AD were treated with PNS for 8 weeks. The effects of PNS on learning and memory abilities, cerebral oxidative stress status, and hippocampus ultrastructure of mice were observed. Moreover, changes of the PTEN-induced putative kinase 1 (PINK1)-Parkin, which regulates ubiquitin-dependent mitophagy, and the recruit of downstream autophagy receptors were investigated. RESULTS: PNS attenuated cognitive dysfunction in SAMP8 mice in the Morris water maze test. PNS also enhanced glutathione peroxidase and superoxide dismutase activities, and increased glutathione levels by 25.92% and 45.55% while inhibiting 8-hydroxydeoxyguanosine by 27.74% and the malondialdehyde production by 34.02% in the brains of SAMP8 mice. Our observation revealed the promotion of mitophagy, which was accompanied by an increase in microtubule-associated protein 1 light chain 3 (LC3) mRNA and 70.00% increase of LC3-II/I protein ratio in the brain tissues of PNS-treated mice. PNS treatment increased Parkin mRNA and protein expression by 62.80% and 43.80%, while increasing the mRNA transcription and protein expression of mitophagic receptors such as optineurin, and nuclear dot protein 52. CONCLUSION: PNS enhanced the PINK1/Parkin pathway and facilitated mitophagy in the hippocampus, thereby preventing cerebral oxidative stress in SAMP8 mice. This may be a mechanism contributing to the cognition-improvement effect of PNS.

Fabrication of high-preformance emulsifier from conjugating maltodextrin onto myofibrillar protein peptide with microwave- ultrasound synergy.

In this study, we systematically investigated the emulsifying capabilities of myofibrillar protein (MP)- and MP peptide (MPP)-based conjugates synthesized through intensification techniques: water bath (WB), microwave, ultrasound, and the combined ultrasound-microwave (UM) methods. Compared with WB, microwave, and ultrasound treatments, the combined UM treatment greatly promoted the glycation reaction because ultrasound and microwave mutually reinforced modification effects. The resultant conjugate structure tended to unfold with more flexible conformation and homogeneous morphology. Moreover, the emulsifying properties of conjugates developed with single and combined ultrasound-assisted glycation displayed substantial improvement, and pre-hydrolysis further enhanced these performances, as observed in the Principal Component Analysis as well. Remarkably, MPP grafted by maltodextrin with the assistance of a combined UM field produced the smallest and most uniform emulsion system, positioning it as the most efficient emulsifier among all the fabricated glycoconjugates. Our study highlighted the potential of synergistically applying ultrasound and microwave techniques to develop a well-performance glycation with an ideal conjugate structure, in which they would be associated into a strong film that provided the robust physical barrier, creaming stability, heat retention, and oxidation resistance. These findings offered a basis for better utilizing complex ultrasonic technology to develop novel and improved MP-based food products.

Protein extraction from chlorella pyrenoidosa microalgae: Green methodologies, functional assessment, and waste stream valorization for bioenergy production.

C. pyrenoidosa, a species of microalgae, has been recognized as a viable protein source for human consumption. The primary challenges in this context are the development of an efficient extraction process and the valorization of the resultant waste streams. This study, situated within the paradigm of circular economy, presents an innovative extraction approach that achieved a protein extraction efficiency of 62 %. The extracted protein exhibited remarkable oil-water emulsifying performances, such as uniform morphology with high creaming stability, suggesting a sustainable alternative to conventional emulsifiers. Additionally, hydrothermal liquefaction technique was employed for converting the residual biomass and waste solution from the extraction process into biocrude. A biocrude yield exceeding 40 wt%, characterized by a carbon content of 73 % and a higher heating value of 36 MJ/kg, were obtained. These findings demonstrate the promising potential of microalgae biorefinery, which is significant for paving toward circular economy and zero-waste society.

Comparison of the Medium-term Outcomes of Anterior Lumbar Discectomy and Fusion with Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Retrospective Cohort Study.

OBJECTIVE: Lumbar degenerative diseases (LDDs) with huge herniation in the left lateral recess or central canal present challenges for oblique lateral lumbar interbody fusion (OLIF) or endoscope-assisted OLIF procedures. Currently, minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is the primary approach for this issue. This study aims to provide a standardized technical description of the anterior lumbar discectomy and fusion (ALDF) and evaluate the medium-term clinical effectiveness of both ALDF and MIS-TLIF techniques. METHODS: A retrospective review was performed on LDDs who underwent ALDF and MIS-TLIF surgery from January 2018 to January 2020. The evaluation encompassed various clinical outcomes, such as the visual analogue scale (VAS) scores for back pain and leg pain (VAS-back, VAS-leg), the Oswestry disability index (ODI), the 36-item short-form health survey mental component summary (SF-36 MCS), and the physical component summary (SF-36 PCS). Additionally, radiological parameters, including disc height (DH), segmental disk angle (SDA), lumbar lordosis (LL), and cross-sectional area (CSA), were assessed. Data including radiculopathy, estimated blood loss, operation time, time of getting out of bed, fusion rate, and complications were recorded. Student's independent samples t test and Pearson's chi-square test were used to compare the differences between groups. RESULTS: In total, 47 patients were treated by ALDF and 48 patients were treated by MIS-TLIF. The ALDF group exhibited statistically significant lower estimated blood loss and earlier time of getting out of bed compared to the MIS-TLIF group (p < 0.05). The ALDF group demonstrated lower VAS-back scores and a higher remission rate of low back pain 3 years after the surgery (p < 0.05). During the entire follow-up period, the ALDF group exhibited higher increases in DH and SDA compared to the MIS-TLIF group (p < 0.05). At 6 months, the fusion rate in the ALDF group was significantly higher than in the MIS-TLIF group (p < 0.05). The comparison revealed no statistically significant differences in complication rates between the two groups (p > 0.05). CONCLUSION: The ALDF could be considered as a viable surgical alternative for the treatment of LDDs that necessitate ventral neural direct decompression. ALDF exhibited favorable medium-term outcomes in patients with LDDs, displaying advantages in facilitating expedited recovery, enhancing radiographic outcomes, and elevating the remission rate of low back pain. Although ALDF presents slightly higher complication rates compared to MIS-TLIF, it does not adversely affect clinical outcomes.

Simultaneous ultrasound and microwave application in myosin-chlorogenic acid conjugation: Unlocking enhanced emulsion stability.

This study investigated the grafting chlorogenic acid (CA) onto myosin, utilizing various techniques including conventional method, ultrasound, microwave, and combination of ultrasound and microwave (UM). The grafting efficiency was as follows: conventional method < microwave < ultrasound < UM. The UM technique manifested the highest CA-binding capacity (80.26 µmol/g myosin) through covalent bonding, and a much shorter time was required for conjugation than conventional method. The conjugation of polyphenol significantly increased the solubility of myosin with reduced aggregation behavior, which was accompanied by structural alterations from ordered structures (α-helix and ß-sheet) to disordered forms. The emulsion stabilized by UM-myosin-CA conjugate exhibited the most homogeneous microstructure with favorable creaming stability. Moreover, the resulting emulsion presented strong oxidation resistance and storage stability. These results illustrate the promising potential of employing CA-grafted myosin, especially when processed using the UM technique, in the development of highly efficient emulsifiers.

Semaphorin4F is a potential biomarker for clinical progression and prognosis in gastric cancer.

BACKGROUND: Semaphorin4F (Sema4F) is a member of the semaphorin family and exhibits important regulatory functions in cancer biology. We aimed to explore the prognostic value and biologic function of Sema4F in gastric cancer (GC) through clinical data, laboratory studies, and bioinformatic methods. METHODS: We investigated Sema4F-related data and the prognostic values of patients with GC based on several databases, including Tumor Immune Estimation Resource (TIMER), the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), The University Of Alabama At Birmingham Cancer Data Analysis Portal (UALCAN) and Kaplan-Meier Plotter. We detected the expression of Sema4F in cell lines and tumor tissues by reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. The prognostic value of Sema4F expression on patient overall survival was analyzed retrospectively using Kaplan-Meier survival and Cox regression analyses. Moreover, we used Kyoto encyclopedia of genes and genomes (KEGG), Gene Ontology (GO) and Gene-set enrichment analysis (GSEA) analyses to explore the relevant pathways of Sema4F in GC. RESULTS: The expression of Sema4F was markedly increased in cancer tissues and cancer cell lines. Furthermore, high Sema4F expression was positively associated with various clinicopathologic data and independently predicted poor prognosis for overall survival in GC. Our functional enrichment analysis revealed that Sema4F was mainly involved in oxidative phosphorylation and tumor-related signaling pathways. CONCLUSIONS: Sema4F may be a valuable prognostic biomarker and a novel target for gastric cancer.

Facile synthesis of spherical covalent organic frameworks for enrichment and quantification of aryl organophosphate esters in mouse serum and tissues.

Here, an imine-linked-based spherical covalent organic framework (COF) was prepared at room temperature. The as-synthesized spherical COF served as an adsorbent in dispersive solid-phase extraction (dSPE), by its virtue of great surface area (1542.68 m2 /g), regular distribution of pore size (2.95 nm), and excellent stability. Therefore, a simple and high-efficiency dispersive solid phase extraction method based on a spherical COF coupled with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established to determine aryl organophosphate esters in biological samples. This approach displayed favorable linearity in the range of 10.0-1000.0 ng/L (r > 0.9989), a high signal enhancement factor (58.8-181.8 folds) with low limits of detection (0.3-3.3 ng/L). Moreover, it could effectively eliminate complex matrix interference to accurately extract seven aryl organophosphate esters from mouse serum and tissue samples with spiked recoveries of 82.0%-117.4%. The as-synthesized spherical COF has been successfully applied in sample preparation. The dSPE-HPLC-MS/MS method based on a spherical COF has potential application to study the pollutants' metabolism in vivo.

PIWIL1 interacting RNA piR-017724 inhibits proliferation, invasion, and migration, and inhibits the development of HCC by silencing PLIN3.

Background: Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Worldwide, liver cancer is the fourth most common cause of cancer-related death. Recent studies have found that PIWI-interacting RNAs (piRNAs) participate in the occurrence and development of various tumors and are closely related to the growth, invasion, metastasis and prognosis of malignant tumors. Studies on the role and functional mechanism of piRNAs in HCC development and progression are limited. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of piR-017724 in both HCC tissues and cells. Based on the clinical data of HCC patients, the clinical and prognostic value of piR-017724 was further analyzed. Then, targeted silencing and overexpressing of piR-017724 in HCC cells was further used to examine the biological functions of piR-017724. In addition, the downstream target protein of piR-017724 was predicted and validated through high-throughput sequencing and public databases. Results: The piR-017724 was significantly downregulated in HCC tissues and cells, and the downregulation of piR-017724 was associated with tumor stage and poor prognosis in HCC. The piR-017724 inhibitor promoted the proliferation, migration and invasion of HCC cells, while the piR-017724 mimic had the opposite effect. However, the piR-017724 did not affect apoptosis of HCC cells. High-throughput sequencing and qRT-PCR confirmed a reciprocal relationship between piR-017724 and PLIN3. Therefore, we speculate that piR-017724 may inhibit the development and progression of HCC by affecting the downstream protein PLIN3. Conclusions: Our study shows that piR-017724, which is lowly expressed in HCC, inhibits the proliferation, migration and invasion of HCC cells and may affect the development of hepatocellular liver cancer through PLIN3, which provides new insights into the clinical application of piR-017724 in the treatment of hepatocellular carcinoma.

Optical single-pixel volumetric imaging by three-dimensional light-field illumination.

Three-dimensional single-pixel imaging (3D SPI) has become an attractive imaging modality for both biomedical research and optical sensing. 3D-SPI techniques generally depend on time-of-flight or stereovision principle to extract depth information from backscattered light. However, existing implementations for these two optical schemes are limited to surface mapping of 3D objects at depth resolutions, at best, at the millimeter level. Here, we report 3D light-field illumination single-pixel microscopy (3D-LFI-SPM) that enables volumetric imaging of microscopic objects with a near-diffraction-limit 3D optical resolution. Aimed at 3D space reconstruction, 3D-LFI-SPM optically samples the 3D Fourier spectrum by combining 3D structured light-field illumination with single-element intensity detection. We build a 3D-LFI-SPM prototype that provides an imaging volume of ∼390 × 390 × 3,800 µm3 and achieves 2.7-µm lateral resolution and better than 37-µm axial resolution. Its capability of 3D visualization of label-free optical absorption contrast is demonstrated by imaging single algal cells in vivo. Our approach opens broad perspectives for 3D SPI with potential applications in various fields, such as biomedical functional imaging.

Dietary taurine supplementation counteracts deoxynivalenol-induced liver injury via alleviating oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation in piglets.

Deoxynivalenol (DON), as a widespread Fusarium mycotoxin in cereals, food products, and animal feed, is detrimental to both human and animal health. The liver is not only the primary organ responsible for DON metabolism but also the principal organ affected by DON toxicity. Taurine is well known to display various physiological and pharmacological functions due to its antioxidant and anti-inflammatory properties. However, the information regarding taurine supplementation counteracting DON-induced liver injury in piglets is still unclear. In our work, twenty-four weaned piglets were subjected to four groups for a 24-day period, including the BD group (a basal diet), the DON group (3 mg/kg DON-contaminated diet), the DON+LT group (3 mg/kg DON-contaminated diet + 0.3% taurine), and the DON+HT group (3 mg/kg DON-contaminated diet + 0.6% taurine). Our findings indicated that taurine supplementation improved growth performance and alleviated DON-induced liver injury, as evidenced by the reduced pathological and serum biochemical changes (ALT, AST, ALP, and LDH), especially in the group with the 0.3% taurine. Taurine could counteract hepatic oxidative stress in piglets exposed to DON, as it reduced ROS, 8-OHdG, and MDA concentrations and improved the activity of antioxidant enzymes. Concurrently, taurine was observed to upregulate the expression of key factors involved in mitochondrial function and the Nrf2 signaling pathway. Furthermore, taurine treatment effectively attenuated DON-induced hepatocyte apoptosis, as verified through the decreased proportion of TUNEL-positive cells and regulation of the mitochondria-mediated apoptosis pathway. Finally, the administration of taurine was able to reduce liver inflammation due to DON, by inactivating the NF-κB signaling pathway and declining the production of pro-inflammatory cytokines. In summary, our results implied that taurine effectively improved DON-induced liver injury. The underlying mechanism should be that taurine restored mitochondrial normal function and antagonized oxidative stress, thereby reducing apoptosis and inflammatory responses in the liver of weaned piglets.

Hierarchically Injectable Hydrogel Sequentially Delivers AntagomiR-467a-3p-Loaded and AntagomiR-874-5p-Loaded Satellite-Cell-Targeting Bioengineered Extracellular Vesicles Attenuating Sarcopenia.

Sarcopenia is a geriatric disease characterized by reduced muscle function and mass. The capacity to self-renew and myogenesis of satellite cells (SCs) declines with age, resulting in age-related sarcopenia. MicroRNAs (miRNAs) can regulate the proliferation and myogenesis of SCs. In this study, it is identified that miR-467a-3p and miR-874-5p could respectively mediate the stemness and myogenesis of SCs by performing bioinformatics analysis. AntagomiR-467a-3p (ant-467a) and antagomiR-874-5p (ant-874) improve the stemness and myogenesis of SCs, respectively. SC-targeting extracellular vesicles (EVs) are constructed by overexpressing TSG101 on the surface of EVs isolated from bone marrow mesenchymal stem cells. Ant-467a loaded EVs (EVs-467a) and ant-874 loaded EVs (EVs-874) are prepared by transferring ant-467a and ant-874 into SC-targeting EVs. EVs-467a and EVs-874 are more effective than ant-467a and ant-874 in promoting the stemness and myogenesis of SCs. Sequentially intermuscular injection of EVs-467a and EVs-874 significantly improve sarcopenia in ovariectomy mice. The effects of multiple injections of EVs-467a and EVs-874 in the treatment of sarcopenia could be achieved by using a hierarchically injectable hydrogel to sustainedly release EVs-467a and EVs-874 in vivo. The findings provide an EV-based SC-targeting antagomiRNAs controlled release strategy as a novel therapy against sarcopenia.

A novel biologically hierarchical hydrogel with osteoblast precursor-targeting extracellular vesicles ameliorates bone loss in vivo via the sequential action of antagomiR-200b-3p and antagomiR-130b-3p.

Osteoporotic fracture is a major health problem plaguing the ageing society, and improving its treatment is an urgent challenge. How to ameliorate bone loss determines the recovery of such fractures. Extracellular vesicle (EV)-loaded hydrogel has the capacity to treat osteoporotic fractures due to its pro-osteogenic property. And balancing proliferation and maturation of osteoblast precursors (OBPs) is of great significance to avoid OBP depletion, which is lacking in current treatment. Based on osteoblastogenic miRNAs, this study aimed to explore the efficacies of the combination of hierarchical hydrogel and EVs altering functional miRNAs level in bone loss. Through bioinformatics analyses, we screened out proliferative gene-targeting miR-200b-3p and osteogenic gene-targeting miR-130b-3p. And antagomiR-200b-3p (ant-200b) enhanced OBP proliferation, and antagomiR-130b-3p (ant-130b) promoted OBP differentiation. After confirming the directional effect of Fibronectin (Fn1) on OBPs, we prepared OBP-targeting EVs. Furthermore, encapsulation of two antagomiRNAs in EVs enhanced the respective effect of ant-200b and ant-130b. Notably, hierarchically injectable hydrogel exerted an effective function in promoting the sequential delivery of EVs-200b and EVs-130b. Importantly, hierarchical hydrogel containing dual EVs effectively ameliorated bone loss. Overall, hierarchical hydrogel based on two antagomiRNAs effectively improves bone loss in vivo due to its role in promoting OBP proliferation and maturation sequentially.