Tumor microenvironment activation amplify oxidative stress promoting tumor energy remodeling for mild photothermal therapy and cuproptosis.

Tumor metabolic reprogramming requires high levels of adenosine triphosphate (ATP) to maintain treatment resistance, which poses major challenges to chemotherapy and photothermal therapy. Especially, high levels of ATP promote copper ion efflux for limiting the curative effect of cuproptosis. Here, an H2S-responsive mesoporous Cu2Cl(OH)3-loading chemotherapeutic cisplatin (CDDP) was synthesized, and the final nanoparticle, CDDP@Cu2Cl(OH)3-CDs (CDCuCDs), was encapsulated by electrostatic action with carbon dots (CDs). CDCuCDs reacted with overproduction H2S in colon tumor to produce photothermic copper sulfide for photothermal therapy. CDDP was released by lysis to achieve chemotherapeutic effects. Importantly, CDDP elevated H2O2 levels in cells through a cascade reaction and continuously transforms H2O2 into highly cytotoxic •OH through chemodynamic therapy between H2O2 and Cu+, which enables nanoparticles to generate •OH and improve the chemotherapeutic efficacy. Highly toxic •OH disrupts mitochondrial homeostasis, prohibiting it from performing normal energy-supplying functions. Down-regulated ATP inhibits heat shock protein expression, which promotes the therapeutic effect of mild photothermal therapy and reduces the efflux of intracellular copper ions, thus improving the therapeutic effect of cuproptosis. Our research provides a potential therapeutic strategy using overproduction H2S responses in tumors, allowing tumor microenvironment-activated •OH nanogenerators to promote tumor energy remodeling for cancer treatment.

Brain responses to intermittent fasting and the healthy living diet in older adults.

Diet may promote brain health in metabolically impaired older individuals. In an 8-week randomized clinical trial involving 40 cognitively intact older adults with insulin resistance, we examined the effects of 5:2 intermittent fasting and the healthy living diet on brain health. Although intermittent fasting induced greater weight loss, the two diets had comparable effects in improving insulin signaling biomarkers in neuron-derived extracellular vesicles, decreasing the brain-age-gap estimate (reflecting the pace of biological aging of the brain) on magnetic resonance imaging, reducing brain glucose on magnetic resonance spectroscopy, and improving blood biomarkers of carbohydrate and lipid metabolism, with minimal changes in cerebrospinal fluid biomarkers for Alzheimer's disease. Intermittent fasting and healthy living improved executive function and memory, with intermittent fasting benefiting more certain cognitive measures. In exploratory analyses, sex, body mass index, and apolipoprotein E and SLC16A7 genotypes modulated diet effects. The study provides a blueprint for assessing brain effects of dietary interventions and motivates further research on intermittent fasting and continuous diets for brain health optimization. For further information, please see ClinicalTrials.gov registration: NCT02460783.

Activation of Nrf2 inhibits atherosclerosis in ApoE-/- mice through suppressing endothelial cell inflammation and lipid peroxidation.

BACKGROUND: Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, is critically involved in the regulation of oxidative stress and inflammation. However, the role of endothelial Nrf2 in atherogenesis has yet to be defined. In addition, how endothelial Nrf2 is activated and whether Nrf2 can be targeted for the prevention and treatment of atherosclerosis is not explored. METHODS: RNA-sequencing and single-cell RNA sequencing analysis of mouse atherosclerotic aortas were used to identify the differentially expressed genes. In vivo endothelial cell (EC)-specific activation of Nrf2 was achieved by injecting adeno-associated viruses into ApoE-/- mice, while EC-specific knockdown of Nrf2 was generated in Cdh5CreCas9floxed-stopApoE-/- mice. RESULTS: Endothelial inflammation appeared as early as on day 3 after feeding of a high cholesterol diet (HCD) in ApoE-/- mice, as reflected by mRNA levels, immunostaining and global mRNA profiling, while the immunosignal of the end-product of lipid peroxidation (LPO), 4-hydroxynonenal (4-HNE), started to increase on day 10. TNF-α, 4-HNE, and erastin (LPO inducer), activated Nrf2 signaling in human ECs by increasing the mRNA and protein expression of Nrf2 target genes. Knockdown of endothelial Nrf2 resulted in augmented endothelial inflammation and LPO, and accelerated atherosclerosis in Cdh5CreCas9floxed-stopApoE-/- mice. By contrast, both EC-specific and pharmacological activation of Nrf2 inhibited endothelial inflammation, LPO, and atherogenesis. CONCLUSIONS: Upon HCD feeding in ApoE-/- mice, endothelial inflammation is an earliest event, followed by the appearance of LPO. EC-specific activation of Nrf2 inhibits atherosclerosis while EC-specific knockdown of Nrf2 results in the opposite effect. Pharmacological activators of endothelial Nrf2 may represent a novel therapeutic strategy for the treatment of atherosclerosis.

A Highly Sustainable Supramolecular Bioplastic Film with Superior Hydroplasticity and Biodegradability.

Massive accumulation of postconsumer plastic waste in eco-system has raised growing environmental concerns. Sustainable end-of-life managements of the indispensable plastic are highly demanding and challenging in modern society. To relieve the plastic menace, herein we present a full life cycle sustainable supramolecular bioplastic made from biomass-derived polyelectrolyte (chitosan quaternary ammonium salt, QCS) and natural sodium fatty acid (sodium laurate, SL) through solid-phase molecular self-assembly (SPMSA), by which the QCS-SL complexes, precipitated from mixing the aqueous solutions, self-assemble to form bioplastic film by mildly pressing at room temperature. The QCS-SL bioplastic films display superior hydroplasticity owing to the water-activated molecular rearrangement and electrostatic bond reconstruction, which allows facile self-healing and reprocessing at room temperature to significantly extend the service lifetime of both products and raw materials. With higher water content, the dynamic electrostatic interactions and precipitation-dissolution equilibrium endow the QCS-SL bioplastic films with considerable solubility in water, which is promising to mitigate the plastic accumulation in aquatic environment. Because both QCS and SL are biocompatible and biodegradable, the dissolved QCS-SL films are nontoxic and environmentally friendly. Thus, this novel supramolecular bioplastic is highly sustainable throughout the whole life cycle, which is expected to open a new vista in sustainable plastic materials.

Synergistic effect of modified anhydrous magnesium carbonate and hexaphenoxycyclotriphosphazene on flame retardancy of ethylene-vinyl acetate copolymer.

Ethylene-vinyl acetate copolymer (EVA) is widely used in various applications; however, its flammability limits its application in wire and cable industries. In this study, 3-methacryloxypropyltrimethoxysilane (KH570) was successfully grafted onto the surface of anhydrous magnesium carbonate (AMC) by alkali activation treatment. The KH570 modified AMC (AMC@KH570) was then introduced into the EVA matrix along with hexaphenoxycyclotriphosphazene (HPCTP) to assess their effects on the flame retardancy and mechanical properties of EVA composites. The results illustrate a significant synergistic effect in enhancing the flame retardancy of EVA composites by using AMC@KH570 and HPCTP, and the limiting oxygen index (LOI) and vertical burning test (UL-94) of EVA filled with 5 wt% HPCTP and 45 wt% AMC@KH570 (mAMC/H-45-5) reached 27.6% and V-0, respectively. The flame retardant mechanism was investigated by thermogravimetric/infrared (TG-IR) spectroscopy and residual carbon composition analysis. The results show that the thermal decomposition of AMC@KH570 and HPCTP consists of gas dilution, free radical quenching, and catalytic carbonization. Furthermore, KH570 works as a bridge to improve the compatibility of AMC and EVA matrix, which offsets the mechanical loss of EVA to some extent. The present research provides a new path to modify AMC and fabricate EVA composites with excellent flame retardant properties.

Chlorella filled poly(lactic acid) (PLA)/poly(butylene adipate-co-terephthalate) (PBAT) blend bio-composites compatible with additive manufacturing processes: Fluorescent and anti-counterfeiting QR codes applications.

Anti-counterfeiting in 3D printing has gained significant attention, however, current approaches often fall short of fully capitalizing on the inherent advantages of personalized manufacturing with this technology. Herein, we propose an embedded anti-counterfeiting scheme for additive manufacturing, accompanied by a novel fluorescent encrypted quick response (QR) method. This approach involves the development of a 3D printing filament utilizing poly(lactic acid) (PLA) and poly(butylene adipate-co-terephthalate) (PBAT) bio-composites as the primary filament matrix, with varying quantities of Chlorella powder incorporated. The resulting filament has a good thermal stability near 200 °C and exhibits a distinctive red fluorescence under ultraviolet light, with the emission peak at 677 nm when excited by 415 nm blue light. Fluorescence imaging analysis confirms that the red fluorescence in 3D printed devices containing Chlorella is a result of the chlorophyll and its derivatives fluorescence effect. The fluorescent encrypted QR codes are inconspicuous in daylight but become easily discernible under ultraviolet light. In the cases of recognizable QR codes, the ∆Eab* values all exceed 35, and the LC/LB values deviate significantly from 1. This research delves into the fluorescence characteristics of Chlorella and highlights its applicability in 3D printing, specifically within the realm of product anti-counterfeiting, presenting a groundbreaking approach.

Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Recyclable and elastic highly thermally conductive epoxy-based composites with covalent-noncovalent interpenetrating networks.

High-power electronic architectures and devices require elastic thermally conductive materials. The use of epoxy resin in thermal management is limited due to its rigidity. Here, based on epoxy vitrimer, flexible polyethylene glycol (PEG) chains are introduced into covalent adaptable networks to construct covalent-noncovalent interpenetrating networks, enabling the elasticity of epoxy resins. Compared to traditional silicone-based thermal interface materials, the newly developed elastic epoxy resin shows the advantages of reprocessability, self-healing, and no small molecule release. Results show that, even after being filled with boron nitride and liquid metal, the material maintains its resilience, reprocessability and self-healing properties. Leveraging these characteristics, the composite can be further processed into thin films through a repeated pressing-rolling technique that facilitates the forced orientation of the fillers. Subsequently, the bulk composites are reconstructed using a film-stacking method. The results indicate that the thermal conductivity of the reconstructed bulk composite reaches 3.66 W m-1 K-1, achieving a 68% increase compared to the composite prepared through blending. Due to the existence of covalent adaptable networks, the inorganic and inorganic components of the composite prepared in this work can be completely separated under mild conditions, realizing closed-loop recycling.

Inventorization and ecological risk assessment of tetrabromobisphenol A and hexabromocyclododecane in sediments from Guangdong coastal area of South China Sea.

Brominated flame retardants (BFRs) exhibit excellent flame retardant properties and are widely used in various industries. Among the common BFRs, tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCDs) pose substantial ecological and human health risks due to their extensive application and long-range transport. This study established 131 sample collection sites along the coast of the South China Sea (SCS) in Guangdong Province to assess the concentration, distribution, inventory, and ecological risk of TBBPA and HBCDs in surface sediments. The concentrations of TBBPA in SCS sediments ranged from < limit of detection (LOD) to 80 µg/kg dry weight (dw), and those of HBCDs from < LOD to 18 µg/kg dw. The diastereoisomers of HBCDs (α-, ß-, and γ-HBCD) in the sediment samples accounted for 36 %, 13 %, and 51 %, respectively. Human activities, particularly those associated with nearby electronic waste disassembly and textile and garment industries, considerably influenced the dispersion of TBBPA and HBCDs. The inventories of TBBPA and HBCDs in Guangdong Province's SCS were estimated to be 3.2 × 105 kg and 7.2 × 104 kg, respectively. The average risk quotient values ranged from <0.01 to 0.016, indicating a low to negligible environmental risk. This study provides deeper insights into the distribution and scientific significance of HBCDs and TBBPA in SCS sediment samples, elucidates the current state of BFR contamination, and offers recommendations for future research on environmental safety and human health in the region.

Pien Tze Huang (PZH) protects endothelial function in diabetic mice.

Endothelial dysfunction is the most common pathological feature of cardiovascular diseases, including diabetes mellitus, hypertension and atherosclerosis. It affects both macro- and micro-vasculatures, causing functional impairment of multiple organs. Pien Tze Huang (PZH) is a well-studied traditional Chinese medicine (TCM) with multiple pharmacological properties that produces therapeutic benefits against colorectal cancer, non-alcoholic steatohepatitis and neurodegenerative diseases. However, it is unknown how PZH affects vascular function under pathological conditions. Therefore, this study aimed to investigate the effect of PZH on endothelial function and the underlying mechanisms in db/db diabetic mice. The results showed that chronic treatment of PZH (250 mg/kg/day, 5 weeks) improved endothelial function by restoring endothelium-dependent relaxation through the activation of the Akt-eNOS pathway and inhibition of endothelial oxidative stress, which increased nitric oxide bioavailability. Furthermore, PZH treatment increased insulin sensitivity and suppressed inflammation in diabetic mice. These new findings suggest that PZH may have vaso-protective properties and the potential to protect against diabetic vasculopathy by preserving endothelial function.

H2S-driven chemotherapy and mild photothermal therapy induced mitochondrial reprogramming to promote cuproptosis.

The elevated level of hydrogen sulfide (H2S) in colon cancer hinders complete cure with a single therapy. However, excessive H2S also offers a treatment target. A multifunctional cascade bioreactor based on the H2S-responsive mesoporous Cu2Cl(OH)3-loaded hypoxic prodrug tirapazamine (TPZ), in which the outer layer was coated with hyaluronic acid (HA) to form TPZ@Cu2Cl(OH)3-HA (TCuH) nanoparticles (NPs), demonstrated a synergistic antitumor effect through combining the H2S-driven cuproptosis and mild photothermal therapy. The HA coating endowed the NPs with targeting delivery to enhance drug accumulation in the tumor tissue. The presence of both the high level of H2S and the near-infrared II (NIR II) irradiation achieved the in situ generation of photothermic agent copper sulfide (Cu9S8) from the TCuH, followed with the release of TPZ. The depletion of H2S stimulated consumption of oxygen, resulting in hypoxic state and mitochondrial reprogramming. The hypoxic state activated prodrug TPZ to activated TPZ (TPZ-ed) for chemotherapy in turn. Furthermore, the exacerbated hypoxia inhibited the synthesis of adenosine triphosphate, decreasing expression of heat shock proteins and subsequently improving the photothermal therapy. The enriched Cu2+ induced not only cuproptosis by promoting lipoacylated dihydrolipoamide S-acetyltransferase (DLAT) heteromerization but also performed chemodynamic therapy though catalyzing H2O2 to produce highly toxic hydroxyl radicals ·OH. Therefore, the nanoparticles TCuH offer a versatile platform to exert copper-related synergistic antitumor therapy.

Surveillance for adverse events following immunization with DTaP-containing combination vaccines in Linping, China, 2019-2022.

Background: The DTaP-Hib and DTaP-IPV/Hib combination vaccine can be used as a substitute for the diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP). We aimed to evaluate the safety of multi-component vaccines containing DTaP by analyzing the reporting rates and characteristics of adverse events following immunization (AEFIs) in Linping District during the years 2019 to 2022. Methods: We obtained data of AEFI and vaccination from the National AEFI Surveillance System of China and Zhejiang Municipal Immunization Information Management System, respectively, during 2019-2022 for a descriptive, epidemiological analysis. Results: The total number of AEFI reported following vaccinations with DTaP-containing combination vaccines was 802 in Linping District from 2019 to 2022. The overall reporting rates of AEFIs following DTaP, DTaP-Hib, and DTaP-IPV/Hib vaccinations were 445.72 (537 cases), 536.29 (45 cases), and 306.13 (220 cases) per 100,000 doses in Linping District from 2019 to 2022, respectively. Only one case of a serious AEFI following DTaP vaccination, with a reporting rate of 0.83 per 100,000 doses. The composition ratio of vaccine product-related reactions for DTaP, DTaP-Hib, and DTaP-IPV/Hib were 99.81, 97.78, and 100.00%, respectively. The composition ratio of coincidental events for DTaP and DTaP-Hib were 0.19 and 2.22%, respectively. The reporting rates of total AEFIs for DTaP-IPV/Hib were lower than for DTaP. The reporting rate of local induration for DTaP-Hib was lower than for DTaP, and the reporting rates of local redness & swelling and local induration for DTaP-IPV/Hib were both lower than for DTaP. DTaP-IPV/Hib had a higher proportion of AEFIs in first quarter compared to DTaP. The reporting rate after the second dose of DTaP-Hib was higher than that of DTaP, and the reporting rates of AEFIs after the first dose and third dose of DTaP-IPV/Hib were lower than DTaP. Conclusion: The reported AEFIs to multi-component vaccines containing DTaP components during 2019-2022 in Linping District were mainly mild vaccine reactions. DTaP-containing combination vaccines demonstrated a good safety profile.

SLA-3d printed building and characteristics of GelMA/HAP biomaterials with gradient porous structure.

Developing a gradient porous scaffold similar to bone structure is gaining increasing attention in bone tissue engineering. The GelMA/HAP hydrogel has demonstrated potential in bone repair. Although 3D printing can build GelMA/HAP with porous structure, fabricating porous GelMA/HAP with gradient porosity and pore size in one step remains challenging. In this paper, a gradient porous structure with controllable pore size, based on gelatin methacryloyl (GelMA) and hydxroxyapatite (HAP), was engineered and printed using stereolithography. Firstly, the GelMA and HAP were mixed to prepare a hydrogel with a solid content ranging from 10 wt% to 50 wt% for stereolithography. Taking advantage of the sol-gel characteristics of GelMA/HAP hydrogel, GelMA/HAP was fed on the workbench through a combination of extrusion and paving to form a thin layer. During the curing of each layer, the hydrogel exposed to the curing of a single UV beam immediately solidified, forming a highly interconnected porous structure. Additionally, the hydrogel outside the scanning range could be further polymerized to form a relatively dense structure due to the residual laser energy. Finally, without gradient structural design or changing printing parameters, the gradient porous structure of bone-like could be printed in a single-step process. By adjusting the curing parameters of the single UV beam and the concentration and size of ceramic in the hydrogel, the printed pore diameter of the spongy structure could be controlled within the range of 50-260 µm, while the thickness of the compact area could be adjusted within 130-670 µm.

Effects of selective serotonin reuptake inhibitors (SSRIs) on suicide: A network meta-analysis of double-blind randomized trials.

The relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide risk in patients with mental disorders remains controversial. We conducted a network meta-analysis to examine the effects of SSRIs on suicide risk in patients with mental disorders. A comprehensive search was conducted across PubMed, Web of Science, PsycINFO, CENTRAL, Wanfang Database, and China National Knowledge Infrastructure for articles published until December 19, 2023. The main outcomes were suicidal ideation and instances of suicidal behavior. We included 29 double-blind randomized trials in our analysis. The findings suggest that SSRIs primarily offer short-term protection against suicidal ideation. By week 2, paroxetine, fluoxetine, escitalopram, and non-SSRI treatments were linked to a decreased suicide risk compared with a placebo, with the exception of sertraline. This protective effect was diminished by week 8. In contrast, studies on instances of suicidal behavior from weeks 1 to 10 found no significant difference in efficacy between SSRIs, non-SSRIs, and placebo. These results indicate that SSRIs may offer short-term protection against suicidal ideation. However, their long-term effectiveness in mitigating suicidal ideation and preventing suicidal behaviors is limited.

A Hydrogel Electrolyte with High Adaptability over a Wide Temperature Range and Mechanical Stress for Long-Life Flexible Zinc-Ion Batteries.

Flexible zinc-ion batteries have garnered significant attention in the realm of wearable technology. However, the instability of hydrogel electrolytes in a wide-temperature range and uncontrollable side reactions of the Zn electrode have become the main problems for practical applications. Herein, N,N-dimethylformamide (DMF) to design a binary solvent (H2 O-DMF) is introduced and combined it with polyacrylamide (PAM) and ZnSO4 to synthesize a hydrogel electrolyte (denoted as PZD). The synergistic effect of DMF and PAM not only guides Zn2+ deposition on Zn(002) crystal plane and isolates H2 O from the Zn anode, but also breaks the hydrogen bonding network between water to improve the wide-temperature range stability of hydrogel electrolytes. Consequently, the symmetric cell utilizing PZD can stably cycle over 5600 h at 0.5 mA cm- 2 @0.5 mAh cm-2 . Furthermore, the Zn//PZD//MnO2 full cell exhibits favorable wide-temperature range adaptability (for 16000 cycles at 3 A g-1 under 25 °C, 750 cycles with 98 mAh g-1 at 0.1 A g-1 under -20 °C) and outstanding mechanical properties (for lighting up the LEDs under conditions of pressure, bending, cutting, and puncture). This work proposes a useful modification for designing a high-performance hydrogel electrolyte, which provides a reference for investigating the practical flexible aqueous batteries.

A peptide selectively recognizes Gram-negative bacteria and forms a bacterial extracellular trap (BET) through interfacial self-assembly.

An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature. The ligand specifically recognizes Gram-negative bacteria via targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks in situ to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the Pseudomonas aeruginosa strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria in vivo. This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.

Photocatalytic degradation of fluoranthene in soil suspension by TiO2/α-FeOOH with enhanced charge transfer capacity.

Polycyclic aromatic hydrocarbons (PAHs) in soil are potentially harmful to human health. However, the use of photocatalysis technology to treat soil contaminated with PAHs remains challenging. Therefore, TiO2/α-FeOOH composite photocatalyst has been synthesized by hydrothermal method and sol-gel method and applied to photocatalytic degradation of fluoranthene in soil. The morphology, elements, crystal structure, optical properties, electrochemical characteristics, and photocatalytic activity of TiO2/α-FeOOH have been characterized. Results showed that TiO2 is tightly fixed on the surface of α-FeOOH, and TiO2/α-FeOOH had higher photocatalytic activity on photocatalytic degradation of fluoranthene in soil under simulated sunlight. The degradation efficiency of TiO2/α-FeOOH is 3.0 and 4.8 times higher than that of TiO2 and α-FeOOH, respectively. This is attributed to enhanced photocatalytic ability by enhancing the transfer capacity of electrons and holes and broadening the spectrum absorption range. The highest degradation efficiency was achieved when the pH of the soil is neutral, the ratio of water/soil is 10:1, and the dosage of catalyst is 50 mg/g. In addition, it was proved that •O2-, h+, and 1O2 are the main active substances in the photocatalysis of TiO2/α-FeOOH. The possible mechanism of a Z-type electron transfer structure was also proposed. The degradation products of fluoranthene were detected, and the degradation pathway was deduced.

Leucine regulates lipid metabolism in adipose tissue through adipokine-mTOR-SIRT1 signaling pathway and bile acid-microbe axis in a finishing pig model.

This study was conducted to explore the regulatory mechanism of leucine (Leu) on lipid metabolism of finishing pigs. Twenty-four Duroc × Landrace × Large cross pigs with an average body weight of 68.33 ± 0.97 kg were randomly allocated into 3 treatment groups with 8 replicates per group (1 pig per replicate). The dietary treatments were as follows: control group (CON), 0.25% Leu group and 0.50% Leu group. The experimental period was 42 d. The results showed as follows. (1) Compared with the CON, 0.25% and 0.50% Leu increased (P < 0.01) the average daily gain (ADG), while the average backfat thickness (ABT) and the ratio of feed intake to body weight gain (F:G ratio) were decreased (P < 0.05). (2) In the 0.25% Leu group, the relative mRNA expression levels of sterol regulatory element binding protein-1c (SREBP1c), recombinant fatty acid transport protein 1 (FATP1), chemerin and peroxisome proliferator-activated receptor γ (PPARγ) were decreased but the level of fatty acid binding protein 4 (FABP4) and fatty acid translocase (FAT/CD36) were increased in backfat tissue. In the 0.25% Leu group, the protein levels of p-Rictor, p-Raptor, p-eIF4E-binding protein 1 (p-4EBP1), p-silent mating type information regulator 2 homolog 1 (p-SIRT1) and acetylation ribosome s6 protein kinase 1 (Ac-S6K1) were increased (P < 0.05). (3) Compared to the CON, the diversity of gut microbiota in the 0.25% Leu group was increased. Principal component analysis showed that the relative abundance of Bacteroidetes, Lactobacillus and Desulfovibrio was higher in the 0.25% Leu group than the CON, but the relative abundance of Firmicutes, Treponema and Shigella was lower than in the CON (P < 0.05). (4) Four different metabolites were screened out from the serum of finishing pigs including allolithocholic acid (alloLCA), isolithocholic acid (isoLCA), ursodeoxycholic acid (UDCA) and hyodeoxycholic acid (HDCA), which correlate to various degrees with the above microorganisms. In conclusion, Leu could promote adipose tissue lipolysis of finishing pigs through the mTOR-SIRT1 signaling pathway, and S6K1 is acetylated at the same time, and the interaction between gut microbiota and bile acid metabolism is also involved.

Pancreatic ß cell derived extracellular vesicles containing surface preproinsulin are involved in glucose stimulated insulin secretion.

AIMS: Extracellular vesicles (EVs) are involved in intercellular communication and are a topic of increasing interest due to their therapeutic potential. The aim of this study was to determine whether human islet-derived EVs contain insulin, and if so, what role do they play in glucose stimulated insulin secretion. MAIN METHODS: We isolated EVs from human islets culture and plasma to probe for insulin. Plasma from hyperglycemic glucose clamp experiments were also used to isolate and measure EV insulin content in response to a secretory stimulus. We performed immunogold electron microscopy for insulin presence in EVs. Co-culture experiments of isolated EVs with fresh islets were performed to examine the effect of EV cargo on insulin receptor signaling. KEY FINDINGS: EVs isolated from culture medium contained insulin. Glucose treatment of islets increased the level of EV insulin. Hyperglycemic glucose clamp experiments in humans also lead to increased levels of insulin in plasma-derived EVs. Immunogold electron microscopy and proteinase K-digestion experiments demonstrated that insulin in EVs predominantly associated with the exterior surface of EVs while western blot analyses uncovered the presence of only preproinsulin in EVs. Membrane-bound preproinsulin in EVs was capable of activating insulin signaling pathway in an insulin receptor-dependent manner. The physiological relevance of this finding was observed in priming of human naïve islets by EVs during glucose stimulated insulin secretion. SIGNIFICANCE: Our data suggest that (1) human islets secret insulin via an alternate pathway (EV-mediated) other than conventional granule-mediated insulin secretion, and (2) EV membrane bound preproinsulin is biologically active.

Application of 3D printing technology for green synthesis of Fe2O3 using ABS/TPU/chlorella skeletons for methyl orange removal.

Photocatalysis is widely acknowledged as an efficient and environmentally friendly method for treating dye-contaminated wastewater. However, the utilization of powdered photocatalysts presents significant challenges, including issues related to recyclability and the potential for secondary pollution. Herein, a novel technique based on 3D printing for the synthesizing of iron oxide (Fe2O3) involving chlorella was presented. Initially, chlorella powders were immobilized within acrylonitrile butadiene styrene (ABS) and thermoplastic polyurethane (TPU) substrate plastics using melt extrusion technology. Subsequently, these composite materials were transformed into ABS/TPU/chlorella skeletons (ATCh40), through fused deposition molding (FDM) technology. The integration of Fe2O3 onto the ATCh40 (ATCh40-Fe2O3) skeletons was accomplished by subjecting them to controlled heating in an oil bath. A comprehensive characterization of the synthesized materials confirms the successful growth of Fe2O3 on the surface of 3D skeletons. This strategy effectively addresses the immobilization challenges associated with powdered photocatalysts. In photocatalytic degradation experiments targeting methyl orange (MO), the ATCh40-Fe2O3 skeletons exhibited a remarkable MO removal rate of 91% within 240 min. Under conditions where the pH of MO solution was maintained at 3, and the ATCh40-Fe2O3 skeletons were subjected to a heat treatment in a 150 °C blast drying oven for 2 hours, the degradation rate of MO remained substantial, achieving 90% removal after 6 cycles. In contrast, when the same synthetic procedure was applied to ABS/TPU (AT) skeletons, the resulting product was identified as α-FeOOH. The MO removal rate by the AT-α-FeOOH skeletons was considerably lower, reaching only 49% after 240 min. This research provided a practical approach for the construction of photocatalytic devices through the use of 3D printing technology.