Valorizing Lycii fructus waste residue into polysaccharide-rich extracts: Extraction methodologies, physicochemical characterization, in vitro activities and economic feasibility.

The high polysaccharide content of Lycii fructus agri-food waste should be reclaimed for value liberation from both environmental and economic perspectives. In this study, waste from L. fructus pigment products was valorized on a bench scale by upcycling into active polysaccharide-rich extracts. The methodological feasibility of polysaccharide recovery from L. fructus waste was evaluated using sequential extraction techniques. Three fractions LFP-30, LFP-100, and LFP-121, were obtained under stepwise increases in temperature and pressure. Highly heterogeneous xyloglucan (XG)-pectin macromolecules composed of linear homogalacturonan (HG) and alternating intra-RG-I-linkers, with topological neutral branches and XG participation, were predominant among the L. fructus polysaccharides (LFPs). Antioxidant activities in LFPs were unaffected by waste resources and severe extraction methodology conditions. Additionally, the direct investment potential of polysaccharide recovery was evaluated for full-scale implementation. This study demonstrated the necessity and feasibility of extracting bioactive polysaccharides with potential applications from L. fructus waste, and provided a sustainable strategy for transforming L. fructus waste disposal problems into value-added products using cost-effective methodologies.

Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases.

BACKGROUND & AIMS: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. METHODS: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by using physical frailty and the frailty index, categorizing participants as nonfrail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. RESULTS: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: HR = 1.66, 95% CI = 1.40-1.97; frailty index: HR = 2.01, 95% CI = 1.67-2.42) and frailty (physical frailty: HR = 3.32, 95% CI = 2.54-4.34; frailty index: HR = 4.54, 95% CI = 3.65-5.66) than in those with nonfrailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as magnetic resonance imaging-derived liver proton density fat fraction > 5%, than the nonfrail group (physical frailty: OR = 1.64, 95% CI = 1.32-2.04; frailty index: OR = 1.48, 95% CI = 1.30-1.68). CONCLUSIONS: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. IMPACT AND IMPLICATIONS: While frailty is common and associated with a poor prognosis in people with MASLD and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with the increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

N-palmitoylethanolamide attenuates negative emotions induced by morphine withdrawal in mice.

Depression and anxiety are prominent symptoms of withdrawal syndrome, often caused by the abuse of addictive drugs like morphine. N-palmitoylethanolamide (PEA), a biologically active lipid, is utilized as an anti-inflammatory and analgesic medication. Recent studies have highlighted PEA's role in mitigating cognitive decline and easing depression resulting from chronic pain. However, it remains unknown whether PEA can influence negative emotions triggered by morphine withdrawal. This study seeks to explore the impact of PEA on such emotions and investigate the underlying mechanisms. Mice subjected to morphine treatment underwent a 10-day withdrawal period, followed by assessments of the effect of PEA on anxiety- and depression-like behaviors using various tests. Enzyme-linked immunosorbent assay was conducted to measure levels of monoamine neurotransmitters in specific brain regions. The findings indicate that PEA mitigated anxiety and depression symptoms and reduced 5-hydroxytryptamine, noradrenaline, and dopamine levels in the hippocampus and prefrontal cortex. In summary, PEA demonstrates a significant positive effect on negative emotions associated with morphine withdrawal, accompanied with the reduction in levels of monoamine neurotransmitters in key brain regions. These insights could be valuable for managing negative emotions arising from morphine withdrawal.

Clinical pathological significance and biological function of PLIN1 in hepatocellular carcinoma: bioinformatics analysis and in vitro experiments.

BACKGROUND & AIMS: Perilipin 1 (PLIN1) is an essential lipid droplet surface protein that participates in cell life activities by regulating energy balance and lipid metabolism. PLIN1 has been shown to be closely related to the development of numerous tumor types. The purpose of this work was to elucidate the clinicopathologic significance of PLIN1 in hepatocellular carcinoma (HCC), as well as its impact on the biological functions of HCC cells, and to investigate the underlying mechanisms involved. METHODS: Public high-throughput RNA microarray and RNA sequencing data were collected to examine PLIN1 levels and clinical significance in patients with HCC. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (RT‒qPCR) were conducted to assess the expression levels and the clinicopathological relevance of PLIN1 in HCC. Then, SK and Huh7 cells were transfected with a lentivirus overexpressing PLIN1. CCK8 assay, wound healing assay, transwell assay, and flow cytometric analysis were conducted to explore the effects of PLIN1 overexpression on HCC cell proliferation, migration, invasion, and cell cycle distribution. Ultimately, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the underlying mechanisms of PLIN1 in HCC progression based on HCC differentially expressed genes and PLIN1 co-expressed genes. RESULTS: PLIN1 was markedly downregulated in HCC tissues, which correlated with a noticeably worse prognosis for HCC patients. Additionally, PLIN1 overexpression inhibited the proliferation, migration, and invasion of SK and Huh7 cells in vitro, as well as arresting the HCC cell cycle at the G0/G1 phase. More significantly, energy conversion-related biological processes, lipid metabolism, and cell cycle signalling pathways were the three most enriched molecular mechanisms. CONCLUSION: The present study revealed that PLIN1 downregulation is associated with poor prognosis in HCC patients and accelerated HCC progression by promoting cellular proliferation, migration, and metastasis, as well as the mechanisms underlying the regulation of lipid metabolism-related pathways in HCC.

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis.

OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Punica granatum L. polysaccharides: A review on extraction, structural characteristics and bioactivities.

Punica granatum L., commonly known as pomegranate, is native to Afghanistan and Iran, and today widely cultivated all over the world. Pomegranate polysaccharides are one of the most important bioactive components of P. granatum, which have a wide range of beneficial biological activities, such as anticancer, immunostimulatory, hepatoprotection, anti-psoriasis and antioxidation. Hot water extraction is currently the most commonly used method to isolate pomegranate polysaccharides. The structural characteristics of pomegranate polysaccharides have been extensively investigated through various advanced modern analytical techniques. This review focuses on the extraction, purification, structural characteristics, biological activities and structure-activity relationships of polysaccharides from Punica granatum. The aim of this article is to comprehensively and systematically summarize recent information of polysaccharides from Punica granatum and to serve as a basis for further research and development as therapeutic agents and functional foods.

Chirality and Curvature on Protein Adsorption and Osteogenesis.

Here we designed enantiomeric lipid-mimetic glutamic acid derivatives (L/D-UG) and investigated their self-assembled chiral nanostructures and performance with the protein adsorption as well as the osteogenesis. It was found that L or D-UG can self-assemble into vesicle bilayers and two-dimensional (2D) nanocrystals via a kinetic and thermodynamic control, respectively. These chiral vesicles and 2D crystals showed differentiated adsorption of proteins by their curvature and chirality. Specifically, fibronectin constituted by L-amino acids adsorbed preferentially on L-UG 2D crystal in a semi-random pattern and L-2D nanocrystal show as the most effective structures to promote bone regeneration. The controlled vesicle and 2D crystal assemblies with different chirality and curvature helps to clarify their determine roles in protein adsorption and osteogenesis.

Size Matters: Influence of Particle Size on Antioxidant, ß-Glucan, and Anti-Inflammatory Potential in Pleurotus floridanus (Agaricomycetes).

Cellular damage resulting from elevated levels of free radicals can lead to persistent health issues. Pleurotus floridanus, an edible white oyster mushroom, is rich in ß-glucans with potent antioxidant and anti-inflammatory properties. In this research, we examined the ß-glucan content, total phenolic content, as well as antioxidant and anti-inflammatory potential of hot water extracts with varying particle sizes (< 75, 75-154, 154-300, and 300-600 µm) of both whole and sliced fruiting bodies of P. floridanus. The findings revealed that the в-glucan content increased as the particle size increased, although no significant differences were observed. Conversely, smaller particle sizes (< 75 µm) of whole and sliced fruiting bodies of P. floridanus exhibited higher phenolic content, 2,2-diphenyl-1-picryl-hy-drazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, and reducing ability compared with larger particle size (> 75 µm). Of the four samples (AW2, AW3, AS1, and AS2) with the highest antioxidant activity selected for anti-inflammatory assays, all demonstrated the ability to reduce nitric oxide and tumor necrosis factor-alpha levels, but did not enhance interleukin-10 expression in lipopolysaccharide-stimulated RAW264.7 cells. Interestingly, particle size < 75 to 300 µm did not appear to influence the anti-inflammatory activity, because no significant differences were observed among the particle sizes. Therefore, a particle size < 300 µm in a P. floridanus hot water extract could serve as a valuable source of antioxidant and anti-inflammatory compounds to counteract the harmful effects of free radicals.

Biomechanical comparison of an intramedullary nail combined with a reconstruction plate combination versus a single intramedullary nail in unstable intertrochanteric fractures with lateral femoral wall fracture: A finite element analysis.

This study aimed to compare the biomechanical performance of an intramedullary nail combined with a reconstruction plate and a single intramedullary nail in the treatment of unstable intertrochanteric femoral fractures with a fracture of the lateral femoral wall (LFW). A three-dimensional finite element (FE) femur model was established from computed tomography images of a healthy male volunteer. A major reverse obliquity fracture line, associated with a lesser trochanteric fragment defect and a free bone fragment of the LFW, was developed to create an AO/OTA type 31-A3.3 unstable intertrochanteric fracture mode. Two fixation styles were simulated: a long InterTAN nail (ITN) with or without a reconstruction plate (RP). A vertical load of 2100 N was applied to the femoral head to simulate normal walking. The construct stiffness, von Mises stress, and model displacement were assessed. The ITN with RP fixation (ITN/RP) provided higher axial stiffness (804 N/mm) than the ITN construct (621 N/mm). The construct stiffness of ITN/RP fixation was 29% higher than that of ITN fixation. The peak von Mises stress of the implants in the ITN/RP and ITN models was 994.46 MPa and 1235.24 MPa, respectively. The peak stress of the implants in the ITN/RP model decreased by 24% compared to that of the ITN model. The peak von Mises stress of the femur in the ITN/RP model was 269.06 MPa, which was lower than that of the ITN model (331.37 MPa). The peak stress of the femur in the ITN/RP model was 23% lower than that of the ITN model. The maximum displacements of the ITN/RP and ITN models were 12.12 mm and 13.53 mm, respectively. The maximum displacement of the ITN/RP model decreased by 12% compared with that of the ITN model. The study suggested that an additional plate fixation could increase the construct stiffness, reduce the stresses in the implant and femur, and decrease displacement after intramedullary nailing. Therefore, the intramedullary nail and reconstruction plate combination may provide biomechanical advantages over the single intramedullary nail in unstable intertrochanteric fractures with a fractured LFW.

iRGD-Guided Silica/Gold Nanoparticles for Efficient Tumor-Targeting and Enhancing Antitumor Efficacy Against Breast Cancer.

Background: Breast cancer presents significant challenges due to the limited effectiveness of available treatments and the high likelihood of recurrence. iRGD possesses both RGD sequence and C-terminal sequence and has dual functions of targeting and membrane penetration. iRGD-modified nanocarriers can enhance drug targeting of tumor vascular endothelial cells and penetration of new microvessels, increasing drug concentration in tumor tissues. Methods: The amidation reaction was carried out between SiO2/AuNCs and iRGD/PTX, yielding a conjugated drug delivery system (SiO2/AuNCs-iRGD/PTX, SAIP@NPs). The assessment encompassed the characterization of the morphology, particle size distribution, physicochemical properties, in vitro release profile, cytotoxicity, and cellular uptake of SAIP@NPs. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed using a small animal in vivo imaging system and a tumor-bearing nude mice model, respectively. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed utilizing a small animal in vivo imaging system and an in situ nude mice breast cancer xenograft model, respectively. Results: The prepared SAIP@NPs exhibited decent stability and a certain slow-release effect in phosphate buffer (PBS, pH 7.4). In vitro studies had shown that, due to the dual functions of transmembrane and targeting of iRGD peptide, SAIP@NPs exhibited strong binding to integrin αvß3, which was highly expressed on the membrane of MDA-MB-231 cells, improving the uptake capacity of tumor cells, inhibiting the rapid growth of tumor cells, and promoting tumor cell apoptosis. The results of animal experiments further proved that SAIP@NPs had longer residence time in tumor sites, stronger anti-tumor effect, and no obvious toxicity to major organs of experimental animals. Conclusion: The engineered SAIP@NPs exhibited superior functionalities including efficient membrane permeability, precise tumor targeting, and imaging, thereby significantly augmenting the therapeutic efficacy against breast cancer with a favorable safety profile.

Unravelling the mechanism of temperature modulated exciton binding energy for MAPbBr3 perovskites.

The excitonic effect significantly influences the optoelectronic characteristics of halide perovskites. However, consensus on the temperature modulated exciton binding energy remains elusive, even for extensively studied materials like MAPbBr3 perovskites. In this study, we utilized UV-vis absorption spectra and the Elliott model to extract the exciton binding energies of MAPbBr3 in the range of 170-290 K. Elliott model fitted results reveal a linear increasing trend in bandgap and exciton binding energy for both cubic and tetragonal phases with temperature, with the tetragonal phase exhibiting a higher increasing rate. Additionally, we found that regardless of the temperature, the strongest absorption peaks are always dominated by the exciton absorption, and our fitted exciton absorption peak blue-shifts with the increase of temperature, accounting for the observed blue-shift of the strongest absorption peak for our fabricated MAPbBr3 sample. However, with the increase of temperature, the weight of continuum state absorption increases significantly, which widens the absorption tails to the longer wavelength, leading to the red-shift of Tauc-plotted optical bandgaps. This is the first work considering the temperature-modulated excitonic properties of halide perovskites, which offers valuable insights into the behavior of MAPbBr3 under varying temperature conditions. After a series of theoretical simulations on the temperature modulated electronic properties, including band structures, carrier effective masses, optical dielectric properties and Born effective charges, we provide rational interpretations for the experimentally observed temperature induced variation of the optical properties. These works are helpful to deepen our understanding of the temperature modulated optical properties of MAPbBr3 perovskites.

Aerobic exercise alleviates skeletal muscle aging in male rats by inhibiting apoptosis via regulation of the Trx system.

Skeletal muscle aging in rats is a reduction in skeletal muscle mass caused by a decrease in the number or volume of skeletal muscle myofibers. Apoptosis has been recognized to play a key role in accelerating the process of skeletal muscle aging in rats. The thioredoxin (Trx) system is a widely expressed oxidoreductase system that controls the cellular reduction/oxidation state and has both potent anti-free radical damage and important pro-growth and apoptosis inhibitory functions. Previous studies have shown that exercise delays skeletal muscle aging. However, it is unclear whether exercise attenuates skeletal muscle aging via the Trx system. Therefore, the present study used the Trx system as an entry point to explore the effect of aerobic exercise to improve skeletal muscle aging in rats and its possible mechanisms, and to provide a theoretical basis for exercise to delay skeletal muscle aging in rats. It was shown that aerobic exercise in senescent rats resulted in increased gastrocnemius index, decreased body weight, increased endurance, decreased skeletal muscle cell apoptosis, increased activity and protein expression of the Trx system, and decreased expression of p38 and ASK1. Based on these findings, we conclude that 10 weeks of aerobic exercise may enhance the anti-apoptotic effect of Trx by up-regulating Trx and Trx reductase (TR) protein expression, which in turn increases Trx activity in rat skeletal muscle, and ultimately alleviates apoptosis in senescent skeletal muscle cells.

Protocol to evaluate rat and mouse cardiomyocyte proliferation in vitro and in vivo.

Here, we present a protocol for the quantitative assessment of rat and mouse cardiomyocyte proliferation both in vitro and in vivo. For the in vivo approach, we describe steps for the isolation of neonatal rat cardiomyocytes and the employment of various indicators to quantify cell proliferation. We then detail in vivo procedures that incorporate comprehensive assays and a genetic lineage tracing strategy to evaluate endogenous cardiomyocyte proliferation. This protocol can be modified to investigate other mammalian cardiomyocyte proliferation. For complete details on the use and execution of this protocol, please refer to Ji et al.1.

Boosting Interfacial Electron Transfer and CO2 Enrichment on ZIF-8/ZnTe for Selective Photoelectrochemical Reduction of CO2 to CO.

Artificial photosynthesis is an effective way of converting CO2 into fuel and high value-added chemicals. However, the sluggish interfacial electron transfer and adsorption of CO2 at the catalyst surface strongly hamper the activity and selectivity of CO2 reduction. Here, we report a photocathode attaching zeolitic imidazolate framework-8 (ZIF-8) onto a ZnTe surface to mimic an aquatic leaf featuring stoma and chlorophyll for efficient photoelectrochemical conversion of CO2 into CO. ZIF-8 possessing high CO2 adsorption capacity and diffusivity has been selected to enrich CO2 into nanocages and provide a large number of catalytic active sites. ZnTe with high light-absorption capacity serves as a light-absorbing layer. CO2 molecules are collected in large nanocages of ZIF-8 and delivered to the ZnTe surface. As evidenced by scanning electrochemical microscopy, the interface can effectively boost interfacial electron transfer kinetics. The ZIF-8/ZnTe photocathode with unsaturated Zn-Nx sites exhibits a high Faradaic efficiency for CO production of 92.9% and a large photocurrent of 6.67 mA·cm-2 at -2.48 V (vs Fc/Fc+) in a nonaqueous electrolyte at AM 1.5G solar irradiation (100 mW·cm-2).

Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.

Sotagliflozin attenuates cardiac dysfunction and depression-like behaviors in mice with myocardial infarction through the gut-heart-brain axis.

Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.