Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy.

As a new form of regulated cell death, ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells. The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells. Due to their high loading and structural tunability, nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting. This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis. Additionally, we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

ß-1,3-d-glucan particles-based "nest" protected co-loaded Rhein and Emodin regulates microbiota and intestinal immunity for ulcerative colitis treatment.

Herein, a ß-1,3-D-glucan based yeast cell wall loaded with co-loaded nanoparticles of Rhein (RH) and Emodin (EMO), was developed for the combined treatment of ulcerative colitis (UC) by modulating gut microbiota and the Th17/Treg cell balance. This was achieved through an oral "nano-in-micro" advanced drug delivery system. Specifically, RH was grafted onto the HA chain via disulfide bonds to synthesize a reduction-sensitive carrier material and then used to encapsulate EMO to form nanoparticles with a specific drug ratio (denoted as HA-RH/EMO NPs). As anticipated, HA-RH/EMO NPs were encased within the "nests"-yeast cell wall microparticles (YPs), efficiently reach the colon and then released gradually, this occurs mainly due to the degradation of ß-1,3-D-glucan by ß-glucanase. Additionally, HA-RH/EMO NPs demonstrated a significant reduction-sensitive effect in GSH stimulation evaluations and a remarkable ability to target macrophages in in vitro cell uptake studies. Notably, HA-RH/EMO NYPs reduced inflammatory responses by inhibiting the PI3K/Akt signaling pathway. Even more crucially, the oral delivery and drug combination methods significantly enhanced the regulatory effects of HA-RH/EMO NYPs on gut microbiota and the Th17/Treg balance. Overall, this research marks the first use of YPs to encapsulate two components, RH and EMO, presenting a promising therapeutic strategy for UC.

Pathogenicity and transcriptomic exploration of Vibrio fortis in Penaeus monodon.

In this study, a strain (recorded as Y6) was isolated from the biofloc pool, its DNA was extracted for 16S rDNA sequencing and compared in the NCBI database, and it was identified as Vibrio fortis. The V. fortis was activated, cultured, and artificially injected into Penaeus monodon to observe the symptoms and calculate the semi-lethal concentration (LC50). It was found that the symptoms of the red leg, an empty stomach, and enlarged hepatopancreas of P. monodon after infection with V. fortis. The LC50 was 4.00 × 107, 2.24 × 107, 1.82 × 107, 1.41 × 107, 7.52 × 106 and 3.31 × 106 CFU/mL at 16, 24, 32, 48, 128, and 144 hpi, respectively. The K-B disk method was used to detect the sensitivity of V. fortis to various antibiotic drugs. V. fortis resisted Ampicillin, Piperacillin, Cefazolin, Cephalothin and Cefoxitin. Highly sensitive to Polymyxin B, Tobramycin, Gentamicin, Cefepime, Cefoperazone and Streptomycin. To explore the molecular response mechanism of V. fortis infection in P. monodon, the hepatopancreas of P. monodon infected with V. fortis at 24 and 48 hpi by transcriptome sequencing, and a total of 347 DEGs were obtained (214 up-regulated DEGs and 133 down-regulated DEGs). In the KEGG pathway enrichment analysis of DEGs, significant changes were found in genes and signaling pathways related to immune system and substance metabolism, including NOD-like receptor signaling pathways, Toll and Imd signaling pathways, C-type lectin receptor signaling pathways and pyruvate metabolism. This study initially revealed the immune response of P. monodon to V. fortis infection from the molecular level and provided a reference for further understanding of the study and control of the vibriosis of shrimp.

"Dual sensitive supramolecular curcumin nanoparticles" in "advanced yeast particles" mediate macrophage reprogramming, ROS scavenging and inflammation resolution for ulcerative colitis treatment.

Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on ß-cyclodextrin (ß-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for "supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects" in "advanced yeast particles", but also provided strong theoretical support multi-effect therapy for UC.

Folic acid-modified lactoferrin nanoparticles coated with a laminarin layer loaded curcumin with dual-targeting for ulcerative colitis treatment.

Curcumin (CUR) is a promising natural compound in ulcerative colitis (UC) treatment, but limited by its low oral bioavailability and poor targeting ability. Therefore, given the targeting action of lactoferrin (LF) by binding to the LF receptors of intestinal epithelial cells (IECs) and of folic acid (FA) by binding to the FA receptors of macrophages, we developed an oral dual-targeting nanosystem. Laminarin (LA)-coated, FA-modified LF nanoparticles (NPs) were used to encapsulate CUR (LA/FA/CUR-NPs) with a food-grade, enzyme-sensitive, and dual-targeting capacity. For the generated NPs, LF improved the loading efficiency of CUR (95.08 %). The LA layer could improve the upper gastrointestinal tract stability of the NPs while improve drug release around colon lesion through ß-glucanase digestion. Based on the cellular uptake evaluation, FA/CUR-NPs were capable of specifically targeting colonic epithelial cells and macrophages through LF and FA ligands, respectively, to enhance the uptake efficiency. Moreover, based on the advantage of the dual-targeting strategy, oral administration of FA/CUR-NPs obviously reduced colitis symptoms by alleviating inflammation, accelerating colonic mucosal barrier repair and restoring the balance of the intestinal microbiota. This dual-targeted nanodesign corresponded to the multi-bioresponsibilities of CUR, thus offering a promising approach in UC treatment.

Recent advances in natural polysaccharides-based controlled release nanosystems for anti-cancer phototherapy.

Phototherapy, which relies on light to trigger phototherapeutic agents (PAs) to generate cytotoxic reactive oxygen species or hyperthermia, has received much attention in cancer treatment. However, traditional PAs have shortcomings such as low water solubility, easy aggregation-induced fluorescence quenching and low target site accumulation efficiency, which severely limit clinical anticancer applications. Naturally derived polysaccharides have attracted great attention in the scientific community in nano-drug delivery systems (NDDS) due to their abundant resources, biocompatibility, targeting ability, bioactivity and so on, which is expected to assist PAs to play a synergistic effect. This article reviews the recent progress of polysaccharides in the field of cancer phototherapy, including the advantages of polysaccharides as nanocarrier materials to deliver PAs; the main mechanism for the preparation of PAs-loaded polysaccharides nanoformulation; construction of polysaccharides-based NDDS for delivery of PAs and its functional modification strategy, hoping to further improve the therapeutic effect of phototherapy against cancer.

Integrated analysis of intestinal microbiota and metabolomic reveals that decapod iridescent virus 1 (DIV1) infection induces secondary bacterial infection and metabolic reprogramming in Marsupenaeus japonicus.

In recent years, with global warming and increasing marine pollution, some novel marine viruses have become widespread in the aquaculture industry, causing huge losses to the aquaculture industry. Decapod iridescent virus 1 (DIV1) is one of the newly discovered marine viruses that has been reported to be detected in a variety of farmed crustacean and wild populations. Several previous studies have found that DIV1 can induce Warburg effect-related gene expression. In this study, the effects of DIV1 infection on intestinal health of shrimp were further explored from the aspects of histological, enzymatic activities, microorganisms and metabolites using Marsupenaeus japonicus as the object of study. The results showed that obvious injury in the intestinal mucosa was observed after DIV1 infection, the oxidative and antioxidant capacity of the shrimp intestine was unbalanced, the activity of lysozyme was decreased, and the activities of digestive enzymes were disordered, and secondary bacterial infection was caused. Furthermore, the increased abundance of harmful bacteria, such as Photobacterium and Vibrio, may synergized with DIV1 to promote the Warburg effect and induce metabolic reprogramming, thereby providing material and energy for DIV1 replication. This study is the first to report the changes of intestinal microbiota and metabolites of M. japonicus under DIV1 infection, demonstrating that DIV1 can induce secondary bacterial infection and metabolic reprogramming. Several bacteria and metabolites highly associated with DIV1 infection were screened, which may be leveraged for diagnosis of pathogenic infections or incorporated as exogenous metabolites to enhance immune response.

Pathogenicity and transcriptome analysis of a strain of Vibrio owensii in Fenneropenaeus merguiensis.

Vibrio is an important conditional pathogen in shrimp aquaculture. This research reported a dominant bacteria strain E1 isolated from a shrimp tank with the method of biofloc culture, which was further identified as Vibrio owensii. To understand the interaction between V. owensii and the host shrimp, we studied the pathogenicity of the V. owensii and the molecular mechanisms of the Fenneropenaeus merguiensis immunity during the Vibrio invasion. Drug susceptibility tests showed that V. owensii was resistant to antibiotics streptomycin oxacillin, tetracycline, minocycline, and aztreonam, but highly sensitive to cefazolin, cefotaxime, and ciprofloxacin, and moderately sensitive to cefotaxime, ampicillin, and piperacillin. Lethal concentration 50 (LC50) test was performed to evaluate the toxicity of V. owensii to F. merguiensis. The LC50 of V. owensii infected F. merguiensis after 24, 48, 72, 96, 120, 144 and 168 h were 1.21 × 107, 1.68 × 106, 6.36 × 105, 2.15 × 105, 7.58 × 104, 5.55 × 104 and 4.33 × 104 CFU/mL. In order to explore the molecular response mechanism of F. merguiensis infected with V. owensii, the hepatopancreas of F. merguiensis were sequenced at 24 hpi and 48 hpi, and a total 40,181 of unigenes were obtained. Through comparative transcriptomic analysis, 86 differentially expressed genes (DEGs) (including 38 up-regulated DEGs, and 48 down-regulated DEGs) and 305 DEGs (including 150 up-regulated DEGs, and 155 down-regulated DEGs) were identified at 24 hpi and 48 hpi, respectively. Annotation and classification analysis of these 391 DEGs showed that most of the DEGs were annotated to metableolic and immune pathways, which indicated that F. merguiensis responded to the invasion through the regulation of material metableolism and immune system genes during V. owensii infection. In the KEGG enrichment analysis, some pathways related to immune response were significantly influenced by V. owensii infection, including phagosome, MAPK signalling pathway and PI3K-Akt signalling pathway. In addition, some pathways related to the warburg effect were also significantly enriched after V. owensii infection, including pyruvate metableolism, glycolysis/gluconeogenesis, and citrate cycle (TAC cycle). Further analysis showed that C-type lectins and ficolin were also play important roles in the immune response of F. merguiensis against V. owensii infection. The current research preliminarily revealed the immune response of F. merguiensis to V. owensii infection at the molecular level, which provided valuable information to further understand the disease control and the interaction between shrimp and Vibrio.

In-situ visualizing selective lignin dissolution of tracheids wall in reaction wood.

As a renewable biological macromolecule with aromatic structure, lignin can serve as matrix substance to maintain cell wall integrity and is regarded as the natural biomass recalcitrance. Substantial differences in the cell wall lignin topochemistry between opposite (Ow) and compression wood (Cw) trachieds in Pinus bungeana Zucc. were visualized during [Emim][OAc] pretreatment at room temperature. The ionic liqiuds treatment induced a more obvious wall swelling for highly lignified Cw tracheids than that of Ow, while dynamic Raman spectra analysis indicated the higher lignin and carbohydrates removal for Ow tracheids. Raman imaging further revealed that both lignin and carbohydrates were dissolved simultaneously within the middle lamella and secondary wall of Ow and pretreatment has little effects on Cw tracheids wall. Moreover, it was demonstrated that lignin composition was the key factor to affect the composition dissolution. In particular, lignin G-units were selectively removed from cell corner middle lamella (52.3 %) and secondary wall (62.0 %) of Ow tracheids. When cotton fiber, as a reference was treated under the same conditions, lattice conversion moving from cellulose I to II occurred. The findings confirmed the important role of lignin compostion in the dissolution behavior of carbohydrate dominant tracheids wall.

ß-1,3-d-Glucan based yeast cell wall system loaded emodin with dual-targeting layers for ulcerative colitis treatment.

Herein, a ß-1,3-d-glucan based microcarrier, yeast cell wall microparticles (YPs), was used to develop a food-source-based nano-in-micro oral delivery system for ulcerative colitis (UC) treatment. Briefly, lactoferrin (Lf), which targets intestinal epithelial cells, was used to encapsulate emodin (EMO) to form nanoparticles (EMO-NPs), and then loaded into YPs with the natural macrophages targeting ability, forming a final formula with two outer-inner targeting layers (EMO-NYPs). These dual-targeting strategy could enhance the dual-effects of EMO in anti-inflammatory and mucosal repair effects respectively. As expected, cell uptake assessment confirmed that EMO-NPs and EMO-NYPs could target on the Lf and dection-1 receptors on the membranes of Caco-2 cells and macrophages, respectively. Importantly, EMO-NYPs showed the best anti-UC effects compared to EMO-NPs and free EMO, by inhibiting NF-κB pathway to anti-inflammation and promoting intestinal mucosa repair via MLCK/pMLC2 pathway. The results show that EMO-NYPs are a promising food-based oral delivery system in anti-UC.