Comparison on emulsifying and emulgelling properties of low methoxyl pectin with varied degree of methoxylation from different de-esterification methods.

Low methoxyl pectin (LMP) with different degree of methoxylation (DM, 40-50 %, 20-30 % and 5-10 %) were prepared from commercially available citrus pectin using high hydrostatic pressure assisted enzymatic (HHP-pectin) and traditional alkaline (A-pectin) de-esterification method. The results showed that both de-esterification methods and DM exhibited LMPs with varied physicochemical, structural, and functional properties. As the DM decreased, LMP showed a decrease in molecular weight (Mw), while an increase in negative charges and rhamnogalacturonan I (RG-I) ratio, accompanied with better emulsion stability, emulsion gel strength and water-holding properties. Relative to A-pectin, HHP-pectin had higher Mw and lower RG-I side chain ratio, contributing to its better thermal stability, apparent viscosity, and emulgelling properties. HHP-pectin with lower DM (5-10 %) showed superior thickening, emulsifying and emulgelling properties, while that with higher DM (40-45 %) had superior thermal stability, which provided alternative for de-esterification and targeted structural modification of pectin.

Potential role of cell wall pectin polysaccharides, water state, and cellular structure on twice "increase-decrease" texture changes during kohlrabi pickling process.

Pickled kohlrabi is a traditional and favored vegetable product in China. During pickling, the hardness, springiness, and chewiness of kohlrabi all experienced a typical change with twice "increase-decrease" trend. However, little is known about its mechanism. In this study, in situ analysis including immunofluorescence, low field nuclear magnetic, and transmission electron microscopy were used to explore the effects of cell wall pectin, water state, and cellular structure on kohlrabi texture changes during pickling. Results revealed that at the early stage, due to the rapid loss of water after three times salting, the cells shrank and the interstitial space reduced, resulting in the first increase on kohlrabi texture. Subsequently, the dehydration-rehydration caused by the first brine processing resulted in the first decrease on kohlrabi texture. Then under the action of PME enzyme, more low-esterified pectin was produced, and chelate-soluble pectin with more branched structure was further formed, leading to another elevation of the sample texture. As the pickling continued, under the combined action of PG and PME, the molecular weight of pectin was decreased and the rigidity of the cell tissue was destroyed, caused kohlrabi texture continued to decline. These researches could provide important information and guidance for better maintaining the texture of pickled vegetables during processing.

Kaempferol attenuates carbon tetrachloride (CCl4)-induced hepatic fibrosis by promoting ASIC1a degradation and suppression of the ASIC1a-mediated ERS.

BACKGROUND: Kaempferol is a flavonoid derived from the herb, Kaempferia galanga L., in addition to exhibiting a wide range of pharmacological properties, kaempferol is also an anti-inflammatory, anti-lipid metabolizing, and anti-oxidative stress agent. The underlying molecular mechanisms of its effects on vascular endothelial growth factor (VEGF) secretion and activation of hepatic stellate cells (HSCs) are yet unknown. Activated HSCs induces VEGF release and extracellular matrix (ECM) accumulation which are important factors in hepatic fibrosis. PURPOSE: Our aim is to explore how kaempferol may affect hepatic fibrosis and the mechanisms behind its effects. METHODS: The in vivo model was Sprague-Dawley rats induced with carbon tetrachloride (CCl4). Histological staining was used to observe histological features of the liver. The levels of (alanine aminotransferase) ALT and (aspartate aminotransferase) AST were detected by the corresponding kits. Platelet-derived growth factor (PDGF) was used to stimulate the HSC-T6 rat hepatic stellate cells. The mechanisms underlying this process were investigated using a variety of molecular approaches, including immunofluorescence, RT-qPCR, and western blotting. Moreover, intracellular Ca2+ were observed by laser confocal microscope. RESULTS: It was found that kaempferol significantly reduced the expression of ASIC1a, VEGF, α-SMA and Collagen-I proteins in a model of CCl4-induced hepatic fibrosis in rats. In HSC-T6, kaempferol inhibits activation of HSCs by decreasing expression of ASIC1a, eIF2α, p-eIF2α and ATF-4. Laser confocal fluorescence showed that kaempferol inhibited Ca2+ influx and reduced Ca2+ concentration around the endoplasmic reticulum. Molecular docking and cellular thermal shift assay (CETSA) results further indicated that kaempferol interacted with ASIC1a. We found that kaempferol may promote the degradation of ASIC1a and inhibited ASIC1a- mediated upregulation of ERS. CONCLUSION: The data from our in vivo experiments demonstrate that kaempferol effectively attenuates hepatic fibrosis. In vitro studies we further propose a novel mechanism of kaempferol against hepatic fibrosis which can interact with ASIC1a and promote ASIC1a degradation while inhibiting the activation and VEGF release of HSCs by suppressing the ASIC1a-eIF2α-ATF-4 signaling pathway.

Tumor-overexpressed enzyme responsive amphiphiles small molecular self-assembly nano-prodrug for the chemo-phototherapy against non-small-cell lung cancer.

Rational design of self-assembly drug amphiphiles can provide a promising strategy for constructing nano-prodrug with high drug loading, smart stimuli-responsive drug release and high tumor selectivity. Herein, we report a small molecular amphiphile prodrug that can self-assemble into multifunctional nano-prodrug for enhanced anticancer effect by the combination of chemotherapy and phototherapy (PDT/PTT). In this prodrug, the simple insertion of quinone propionate into hydrophilic drug Irinotecan (Ir) generates suitable amphiphiles that endow a good self-assembly behavior of the prodrug and transform it into a stable and uniform nanoparticle. Interestingly, this excellent self-assembly behavior can load phototherapy agent ICG to form a multifunctional nano-prodrug, thereby enhancing the chemotherapeutic effect with PDT/PTT. Importantly, the quinone propionic acid moiety in the prodrug showed a high sensitivity to the overexpressed NAD(P)H:quinone oxidoreductase-1 (NQO1) in non-small cell lung cancer (NSCLC) cells, and this sensitivity enables the disassembly of nano-prodrug and efficient NQO1-responsive drug release. To further enhance the drug accumulation on tumor tissue and migrate the blood clearance, a biomimetic nano-prodrug has been successfully explored by coating hybrid membrane on the above nano-prodrug, which displays high selective inhibition of tumor growth and metastasis on NSCLC mice model. Our findings provide new insights into the rational design of tumor-overexpressed enzyme responsive nano-prodrug for cancer combinational therapy.

Soybean lecithin and cholesterol-loaded cyclodextrin in combination to enhances the cryosurvival of dairy goat semen.

The objective of the study was to examine the effect of soy lecithin (SL) and cholesterol loaded cryclodestrin (CLC) on cryo-survival of sperm cryopreserved in the presence or absence of seminal plasma in Saanen dairy goats. Tris-based dilutions containing various concentrations of SL (0, 0.5%, 1.0% or 2.0%) and CLC (0, 2.0 g/L, 4.0 g/L or 6.0 g/L CLC) were used to cryopreserve Saanen dairy goat sperm. The quality of frozen-thawed sperm, including progressive motility, viability, acrosome and plasma membrane integrity, as well as fertility were detected. Results found that the optimal combination of the two cryoprotectants was 1.0% SL+4.0 g/L CLC, which significantly increased progressive motility, viability, acrosome and plasma membrane integrity of frozen thawed sperm. The impact of the two cryoprotectants in combination was not affected by the presence of seminal plasma. The conception rates obtained after artificial insemination using sperm cryopreserved with and without seminal plasma were 88.89% and 91.67% (P > 0.05), respectively. The respective values for average number of litter sizes were 1.55 ± 0.17 and 1.56 ± 0.21 (P > 0.05). Therefore, this study improved the cryopreservation efficiency of goat semen, enhanced the sperm cryosurvival, and layed a foundation for the wide application of frozen goat semen.

Hotspots and future trends of phosphorus recycling from livestock manure: A bibliometric review.

In recent decades, the importance of managing the earth's dwindling phosphorus (P) has grown exponentially, as have efforts to develop a circular economy. Livestock manure represents a P-rich waste product, so recycling P from livestock manure has garnered the attention of scholars worldwide. Based on a global database from 1978 to 2021, this study presents the current status of recycling P from livestock manure and proposes strategies for efficient P utilization. Unlike traditional review articles, this work establishes a visual collaborative network on P recycling from livestock manure of research areas, countries, institutions, and authors through a bibliometric analysis using Citespace and VOSviewer software. The co-citation analysis of literature revealed the development of the main research content in this field, and further clustering analysis illustrated the current key research directions. Keyword co-occurrence analysis identified the hotspots and new frontiers of research in this field. According to the results, the United States was the most influential and actively contributing nation, and China was the country with the tightest international ties. The most popular research area was environmental science, and the Bioresource Technology published the largest number of papers in this area. The research priority was the technologies development of P recycling from livestock manure, of which the most used method was struvite precipitation and biochar adsorption. Subsequently, evaluation is also essential, including the economic benefits and environmental impacts of the recycling process by life cycle assessment and substance flow analysis, as well as the agronomic efficiency of the recycled products. New directions for technological innovation in recycling P from livestock manure and potential risks in the recycling process are explored. The results of this study may provide a framework for understanding the mechanisms of P utilization in livestock manure, and support the overall popularization of P recycling technology from livestock manure.

Emulsifying properties, in vitro digestive characteristics, and ß-carotene bioaccessibility of mandarin peel pectin emulsions prepared with different carrier oil phases.

Mandarin peel pectin (MPP) emulsions were prepared with different oil phase loadings with or without ß-carotene, and their emulsifying characteristics, digestive properties and ß-carotene bioaccessibility were investigated. Results revealed that all MPP emulsions exhibited good loading efficiency for ß-carotene, while their apparent viscosity and interfacial pressure (π) of MPP emulsions increased significantly after the addition of ß-carotene. Emulsification of MPP emulsions as well as digestibility were significantly dependent on the kind of oil. MPP emulsions prepared with long-chain triglycerides (LCT) oil (soybean, corn, and olive oil) exhibited higher volume average particle size (D4,3), apparent viscosity, π values, and bioaccessibility of carotene compared to those prepared with medium-chain oils (MCT). MPP emulsions with LCT rich in monosaturated fatty acids (olive oil) had the highest ß-carotene encapsulation efficiency, bioaccessibility, etc. than from other oils. This study provides a theoretical basis for the efficient encapsulation and high bioaccessibility of carotenoids with pectin emulsions.

Nano-Econazole Enhanced PD-L1 Checkpoint Blockade for Synergistic Antitumor Immunotherapy against Pancreatic Ductal Adenocarcinoma.

Insufficienct T lymphocyte infiltration and unresponsiveness to immune checkpoint blockade therapy are still major difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). Although econazole has shown promise in inhibiting PDAC growth, its poor bioavailability and water solubility limit its potential as a clinical therapy for PDAC. Furthermore, the synergistic role of econazole and biliverdin in immune checkpoint blockade therapy in PDAC remains elusive and challenging. Herein, a chemo-phototherapy nanoplatform is designed by which econazole and biliverdin can be co-assembled (defined as FBE NPs), which significantly improve the poor water solubility of econazole and enhance the efficacy of PD-L1 checkpoint blockade therapy against PDAC. Mechanistically, econazole and biliverdin are directly released into the acidic cancer microenvironment, to activate immunogenic cell death via biliverdin-induced PTT/PDT and boost the immunotherapeutic response of PD-L1 blockade. In addition, econazole simultaneously enhances PD-L1 expression to sensitize anti-PD-L1 therapy, leading to suppression of distant tumors, long-term immune memory effects, improved dendritic cell maturation, and tumor infiltration of CD8+ T lymphocytes. The combined FBE NPs and α-PDL1 show synergistic antitumor efficacy. Collectively, FBE NPs show excellent biosafety and antitumor efficacy by combining chemo-phototherapy with PD-L1 blockade, which has promising potential in a precision medicine approach as a PDAC treatment strategy.

Comparison of phosphorus species in livestock manure and digestate by different detection techniques.

Phosphorus (P) species characterize the effectiveness of the P fertilizer. In this study, the P species and distribution in different manures (pig manure, dairy manure and chicken manure) and their digestate were systematically investigated through combined characterization methods of Hedley fractionation (H2OP, NaHCO3-P, NaOH-P, HCl-P, and Residual), X-ray diffraction (XRD) and nuclear magnetic resonance (NMR) techniques. The results from Hedley fractionation showed that >80 % of P in the digestate was inorganic and the HCl-P content in manure increased significantly during anaerobic digestion (AD). XRD manifested that insoluble hydroxyapatite and struvite belonging to HCl-P were presented during AD, which was in agreement with the result of Hedley fractionation. 31P NMR spectral analysis revealed that some orthophosphate monoesters were hydrolyzed during AD, meanwhile the orthophosphate diester organic phosphorus like DNA and phospholipids content has increased. After characterizing P species by combining these methods, it was found that chemical sequential extraction could be an effective way to fully understand the P in livestock manure and digestate, with other methods used as auxiliary tool depending on the purpose of studies. Meanwhile, this study provided a basic knowledge of utilizing digestate as P fertilizer and minimizing the risk of P loss from livestock manure. Overall, applying digestates can minimize the risk of P loss from directly applied livestock manure while satisfying plant demands, and is an environmentally friendly P fertilizer.

Mechanism of Chaihu Longgu oyster adjusted decoction for the treatment of depression based on network pharmacology and molecular docking technology.

Background: Depression is a common clinical psychiatric disorder that is responsible for health-related disease burdens globally. According to traditional Chinese medicine (TCM), mental disorders and qi stagnation are important pathogenic mechanisms of depression. The Chaihu Longgu Oyster Decoction, which has been documented in the Shanghanlun (Treatise on Typhoid), is widely used to treat various affective disorders. Methods: Network pharmacology and molecular docking technology were used to investigate the material basis and mechanism of action of the Chaihu Longgu oyster adjusted decoction in treating depression. The main pharmacological substance bases, possible targets, and pathways of Chaihu Longgu oyster adjusted decoction in treating depression were visualized by constructing a "component-pathway-target" network. Results: Quercetin, 7-methoxy-2-methylisoflavone, baicalein, kaempferol, and lignan are the main practical chemical components in Chaihu Longgu oyster adjusted decoction. The Chaihu Longgu oyster adjusted decoction regulates 74 protein targets and 142 pathways associated with depression. Its molecular mechanism involves inhibiting neuroinflammation and improving neurotransmitter function, neuroplasticity, etc. Conclusions: The underlying mechanism of the anti-depressive effect of the Chaihu Longgu oyster adjusted decoction may involve neuroinflammatory response reduction and improvement of neurotransmitter function and neuroplasticity. This study revealed the mechanism of action of the Chaihu Longgu oyster adjusted decoction in the treatment of depression through network pharmacology, which provides a scientific basis for clinical application.

Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy.

BACKGROUND: Colorectal cancer (CRC) is a common malignancy with the second highest mortality and the third highest morbidity worldwide. However, the overall survival of patients is unsatisfactory, thus requiring more effective clinical strategies. Celastrol (CLT), a natural bioactive compound, has been reported to induce reactive oxygen species (ROS)-mediated apoptosis to exhibit significant antitumor effects against CRC. However, the poor water solubility, low targeting ability, and bioavailability of CLT have limited its application, and CLT-induced protective autophagy weakens its therapeutic efficiency. RESULTS: We designed a targeted chemo-phototherapy nanoplatform (HCR NPs) to improve the application of CLT. The codelivery of IR820 and CLT in HCR NPs solved the water-soluble problem of CLT and enhanced apoptosis via IR820-mediated hyperthermia. In addition, hydroxychloroquine (HCQ) conjugated to hyaluronic acid (HA) not only increased the active targeting of HCR NPs but also inhibited CLT-induced protective autophagy to exacerbate apoptosis, thus achieving an amplified antitumor effect. Importantly, the HCR NPs exhibited an excellent therapeutic effect on CRC both in vitro and in vivo. CONCLUSION: The HCR NPs presented in this study may not merely provide a new reference for the clinical application of CLT but also result in an attractive strategy for CRC treatment.

Carbon footprint of dairy manure management chains in response to nutrient recovery by aerobic pre-treatment.

Aerobic pre-treatment of liquid dairy manure has previously been reported as an effective nutrient export and emissions mitigation approach. The first objective of this study was to experimentally determine the optimal intermittent aeration ratio for nutrient recovery from liquid dairy manure through an on-site pilot-scale reactor to partially reduce the required energy for the aerobic process. The second objective was to theoretically investigate the total carbon footprints of direct manure spreading on croplands and permanent manure storage in open anaerobic lagoons in response to nutrient removal by the optimal determined intermittent aerobic treatment ratio. Four scenarios (S) were included; S1 was the traditional scenario of manure spread on croplands without the aerobic pre-treatment, S2 was the modified scenario of manure spread on croplands that included the aerobic pre-treatment, S3 was the traditional scenario of manure storage in lagoons, and S4 was the modified scenario of manure storage in lagoons that included the aerobic pre-treatment. The results showed that comparable nutrient removal efficiencies could be obtained with a 5:1 intermittent aeration ratio. Total nitrogen (TN) and total phosphorus (TP) were recovered were 41.5 ± 1.3% and 37.0 ± 4.0%, respectively, in ammonium sulfate and phosphorus-rich sludge, while 55.3 ± 1.4% of the chemical oxygen demand (COD) was removed. The estimated total carbon footprint for S1, S2, S3, and S4 were 24.4, 37.9, 45.3, and 45.9 kg CO2-eqton-1, respectively. However, the total carbon footprint of S2' and S4', which used renewable-based energy to run the reactor instead of fossil-based energy used in S2 and S4, were estimated to 29.5 and 37.5 kg CO2-eqton-1, respectively. Clearly, applying the aerobic pre-treatment increased the total carbon footprint of all cases except S4', in which the total carbon footprint was mitigated by -17.2%. Accordingly, the aerobic pre-treatment is only recommended in the case of S4' from a carbon footprint point of view although it is an effective nutrient recovery technology.

Composition of Chinese Medicine in Hanhou Anshen Incense Based on Gas Chromatography-Mass Spectrometry.

Objective: Our aim was to analyze and study the medicinal components of Hanhou Anshen incense by headspace static injection gas chromatography-mass spectrometry (GC-MS). Methods: After sample preparation, the results were analyzed by chromatography, and the drug components in Hanhou Anshen incense were analyzed according to the total ion flow pattern. Results: A total of 11 drug components of Hanhou Anshen incense were analyzed. Conclusion: This method is applicable to the analysis of the drug composition of Hanhou Anshen incense-which contains a wide variety of drug ingredients-that can provide a theoretical and material basis for the study of improving insomnia.

Exploiting Polyphenol-Mediated Redox Reorientation in Cancer Therapy.

Polyphenol, one of the major components that exert the therapeutic effect of Chinese herbal medicine (CHM), comprises several categories, including flavonoids, phenolic acids, lignans and stilbenes, and has long been studied in oncology due to its significant efficacy against cancers in vitro and in vivo. Recent evidence has linked this antitumor activity to the role of polyphenols in the modulation of redox homeostasis (e.g., pro/antioxidative effect) in cancer cells. Dysregulation of redox homeostasis could lead to the overproduction of reactive oxygen species (ROS), resulting in oxidative stress, which is essential for many aspects of tumors, such as tumorigenesis, progression, and drug resistance. Thus, investigating the ROS-mediated anticancer properties of polyphenols is beneficial for the discovery and development of novel pharmacologic agents. In this review, we summarized these extensively studied polyphenols and discussed the regulatory mechanisms related to the modulation of redox homeostasis that are involved in their antitumor property. In addition, we discussed novel technologies and strategies that could promote the development of CHM-derived polyphenols to improve their versatile anticancer properties, including the development of novel delivery systems, chemical modification, and combination with other agents.

Nanoengineering a Zeolitic Imidazolate Framework-8 Capable of Manipulating Energy Metabolism against Cancer Chemo-Phototherapy Resistance.

Chemo-phototherapy has emerged as a promising approach to complement traditional cancer treatment and enhance therapeutic effects. However, it still faces the challenges of drug efflux transporter-mediated chemoresistance and heat shock proteins (HSPs)-mediated phototherapy tolerance, which both depend on an excessive supply of adenosine triphosphate. Therefore, manipulating energy metabolism to impair the expression or function of P-glycoprotein (P-gp) and HSPs may be a prospective strategy to reverse cancer therapeutic resistance. Herein, a chondroitin sulfate (CS)-functionalized zeolitic imidazolate framework-8 (ZIF-8) chemo-phototherapy nanoplatform (CS/ZIF-8@A780/DOX NPs) is rationally designed that is capable of manipulating energy metabolism against cancer therapeutic resistance by integrating the photosensitizer IR780 iodide (IR780)-conjugated atovaquone (ATO) (A780) and the chemotherapeutic agent doxorubicin (DOX). Mechanistically, ATO and zinc ions that are released in the acidic tumor microenvironment can lead to systematic energy exhaustion through disturbing mitochondrial electron transport and the glycolysis process, thus suppressing the activity of P-gp and HSP70, respectively. In addition, CS is used on the surface of ZIF-8@A780/DOX NPs to improve the targeting capability to tumor tissues. These data provide an efficient strategy for manipulating energy metabolism for cancer treatment, especially for overcoming cancer chemo-phototherapy resistance.

Metabolic Basis of Cognitive Improvement Associated With Active B Vitamin Supplementation in Cognitively Impaired Elderly Subjects - A Metabolomics Study.

Intervention studies with active B vitamin supplementation in cognitively impaired individuals have yielded varying results in randomized controlled trials. In addition, a negative interaction of active B vitamin supplementation with aspirin usage on cognitive outcome was noted, but the molecular basis of the interaction has largely remained unknown. To investigate the metabolic basis of cognitive improvement brought about by active B vitamin supplementation, we conducted an extensive metabolomics analysis covering 302 identified metabolites on the baseline and 24-month serum samples from a cohort of 137 subjects randomly assigned to active supplementation or placebo. Pathway analysis uncovered enhanced gluconeogenesis and War-burg effects underlying cognitive improvement in non-aspirin users supplemented with active B vitamins. In addition, metabolomics revealed that aspirin usage may interact with B vitamin supplementation by altering gut microbial metabolism, particularly in terms of propionate production. Lastly, our omics data suggest that varying capacities to assimilate B vitamins at baseline, possibly mediated by differences in gut microbial composition, may underlie variations in inter-individual responses to active B vitamin supplementation.

Response of phosphorus speciation to organic loading rates and temperatures during anaerobic co-digestion of animal manures and wheat straw.

The world is facing huge phosphate (P) shortage and anaerobic digestion (AD) is a recognized technology to promote nutrient (N and P) recycling. The composition of P speciation in the digestate is essential for the fertilizing effect. However, how P speciation in the digestates interacts with the AD process conditions is unknown. Therefore, interaction of P speciation in digestates with AD process conditions was investigated by using a chemical sequential extraction method (Hedley fractionation) and X-ray diffraction; specifically, the effects of organic loading rate (OLR), temperature, and substrate composition were investigated. The results showed that OLR and feedstock affected P speciation in the digestate significantly due to different ion species and ionic strengths. The H2O-P concentration in chicken manure with straw (CMS) and dairy manure with straw (DMS) digestates decreased by 44.04-48.76% and 48.88-50.49%, respectively, as the OLR increased from 2 to 4 kg VS m-3 d-1. Simultaneously, HCl-P increased by 38.02-44.01% in the CMS digestates due to Ca-P and Mg-P formation, indicating that Ca-P and Mg-P formation was positively correlated with OLR, whereas P mobility decreased. Further, thermophilic temperature conditions were more conducive for the formation of insoluble P than mesophilic temperature conditions in the digestates due to the thermodynamic driving force of the reactions. The results would facilitate the understanding of P transformation in the AD process under the influence of feedstock, OLR, and temperature. From the viewpoint of nutrient management, lower OLR and temperature are more beneficial for a fast P availability, whereas higher OLR and temperature are more helpful for storage and export because of P precipitated into solid phase of digestate.

A biomimetic nanodrug self-assembled from small molecules for enhanced ferroptosis therapy.

Ferroptosis drugs often induce oxidative damage or block antioxidant defense due to the key mechanism of ferroptosis involved in cancer treatment, regulating the intracellular redox balance. However, these ferroptosis drugs are unstable during systemic circulation, and they lack tumor-targeting capability. Herein, we developed a stimuli-responsive and cell membrane-coated nanodrug for the simultaneous delivery of two ferroptosis drugs, an iron-chelating drug as a ROS inducer and sorafenib as an antioxidase inhibitor. The coating of the cancer cell membrane over the nanodrug can enhance the tumor-targeting capability and improve the stability in the blood circulation. In addition, the nanodrug exhibits sensitive drug release profiles in response to glutathione (GSH) and reactive oxygen species (ROS) in tumor microenvironments due to the dynamic diselenide bonds. The released iron-chelating drug and sorafenib not only produce hydroxyl radicals (˙OH) to induce ferroptosis, but also inhibit the expression of GPX4 to mitigate the ferroptosis resistance. Excitingly, the systemic administration of this biomimetic nanodrug displays superior antitumor and anti-metastatic effects in tumor-bearing mice. Our findings provide a promising therapeutic strategy for the co-delivery of ferroptosis inducers and antioxidase inhibitors to strengthen the therapeutic efficacy of ferroptosis.

Lactobacillus plantarum CCFM1143 Alleviates Chronic Diarrhea via Inflammation Regulation and Gut Microbiota Modulation: A Double-Blind, Randomized, Placebo-Controlled Study.

Irritable bowel syndrome with diarrhea and functional diarrhea are both functional bowel disorders that cause chronic diarrhea. Chronic diarrhea is closely related to daily life and the psychological condition of diarrhea in patients, and probiotics can play a significant role in alleviating chronic diarrhea in some research. Lactobaccilus plantarum CCFM1143 can relieve diarrhea in mice caused by enterotoxigenic Escherichia coli (ETEC); however, its clinical effects remain unclear. This study aimed to assess the effects of CCFM1143 as a therapy for chronic diarrhea patients. Fifty-five patients with chronic diarrhea were randomly assigned into the probiotic group (n = 28) and the placebo group (n = 27), receiving the routine regimen with or without probiotics for 4 weeks, respectively. CCFM1143 can mitigate the apparent clinical symptoms and improve the health status and quality of life of patients. In addition, it could inhibit the increase in interleukin 6 (IL-6) and the decrease in motilin; modulate the short-chain fatty acids, especially acetic and propionic acids; and regulate the gut microbiota, particularly reducing the abundance of Bacteroides and Eggerthella and enriching the abundance of Akkermansia, Anaerostipes, and Terrisporobacter. In addition, treatment with probiotics showed clinical effectiveness in managing chronic diarrhea when compared with the placebo group. The findings could help to develop and further the application of probiotics for chronic diarrhea.

Dietary serine supplementation: Friend or foe?

Serine lies at a critical node in biological processes involved in supplying intermediates for redox homeostasis, nucleotide, or lipid biosynthesis and one-carbon metabolism-coupled methyl donor production. Recently, dietary serine supplementation has been reported to modulate cellular serine levels and ameliorate neurological abnormalities induced by serine deficiency. Moreover, growing evidence showed that serine supplementation also alleviates fatty liver, encephalopathy, diabetes mellitus, and related complications, indicating the possibility of serine supplementation as a complementary therapeutic option. However, considering the serine addiction observed in tumorigenesis and tumor development, limitations may exist regarding the application of dietary serine supplementation in patients with cancer. Here, we assess recent research toward the mechanistic understanding of serine supplementation in various diseases to improve our cognition on modulating serine levels in different patients.