The important role of ferroptosis in inflammatory bowel disease.

Ferroptosis is a type of regulated cell death that occurs due to the iron-dependent accumulation of lethal reactive oxygen species (ROS) from lipids. Ferroptosis is characterized by distinct morphological, biochemical, and genetic features that differentiate it from other regulated cell death (RCD) types, which include apoptosis, various necrosis types, and autophagy. Recent reports show that ferritin formation is correlated to many disorders, such as acute injury, infarction, inflammation, and cancer. Iron uptake disorders have also been associated with intestinal epithelial dysfunction, particularly inflammatory bowel disease (IBD). Studies of iron uptake disorders may provide new insights into the pathogenesis of IBD, thereby improving the efficacy of medical interventions. This review presents an overview of ferroptosis, elucidating its fundamental mechanisms and highlighting its significant involvement in IBD.

Molecular Mechanism Study of Dietary Fiber Lignin Intervention in Ulcerative Colitis through GPR37.

Lignin is dietary fiber from plant cell walls with multiple biological antioxidant and anti-inflammatory activities. However, whether lignin protects from ulcerative colitis (UC) and underlying mechanisms is unclear. Herein, UC mouse modeling was established with dextran sulfate sodium (DSS) and treatment with lignin for 1 week. Results showed that lignin inhibited the disease activity index (DAI), histological damage, and cell death in UC mice. We also found that lignin reversed the alterations of ferroptotic features in DSS-induced mice and ferroptotic cells, as evidenced by increased expression of GPX4 and 4-HNE and decreased transferrin expression, ameliorating the phenomenon of iron overload, GSH depletion, and ROS and MDA production. Furthermore, the increased expression of NRF2 was observed in IECs under lignin treatment. Also, the upstream regulatory molecule ERK of NRF2 was activated. Further research revealed that lignin can bind GPR37. Meanwhile, lignin was able to alleviate colitis by improving the composition of the intestinal flora in DSS mice and its effect was similar to that of 5-ASA. Taken together, these findings suggest that lignin protects against ferroptosis in UC by combining GPR37 and activating the ERK-NRF2-GPX4 signaling axis, which provides new ideas for clinical intervention in the treatment of UC.

DNA methylation-mediated ROS production contributes to seed abortion in litchi.

Although there is increasing evidence suggesting that DNA methylation regulates seed development, the underlying mechanisms remain poorly understood. Therefore, we aimed to shed light on this by conducting whole-genome bisulfite sequencing using seeds from the large-seeded cultivar 'HZ' and the abortive-seeded cultivar 'NMC'. Our analysis revealed that the 'HZ' seeds exhibited a hypermethylation level compared to the 'NMC' seeds. Furthermore, we found that the genes associated with differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were mainly enriched in the reactive oxygen species (ROS) metabolic pathway. To investigate this further, we conducted nitroblue tetrazolium (NBT) and 2,7-Dichlorodihydrofluorescein (DCF) staining, which demonstrated a significantly higher amount of ROS in the 'NMC' seeds compared to the 'HZ' seeds. Moreover, we identified that the gene LcGPX6, involved in ROS scavenging, exhibited hypermethylation levels and parallelly lower expression levels in 'NMC' seeds compared to 'HZ' seeds. Interestingly, the ectopic expression of LcGPX6 in Arabidopsis enhanced ROS scavenging and resulted in lower seed production. Together, we suggest that DNA methylation-mediated ROS production plays a significant role in seed development in litchi, during which hypermethylation levels of LcGPX6 might repress its expression, resulting in the accumulation of excessive ROS and ultimately leading to seed abortion.

Sustainable cellobionic acid biosynthesis from starch via artificial in vitro synthetic enzymatic biosystem.

Cellobionic acid (CBA), a kind of aldobionic acid, offers potential applications in the fields of pharmaceutical, cosmetic, food, and chemical industry. To tackle the high cost of the substrate cellobiose in CBA production using quinoprotein glucose dehydrogenase, this study developed a coenzyme-free and phosphate-balanced in vitro synthetic enzymatic biosystem (ivSEBS) to enable the sustainable CBA synthesis from cost-effective starch in one-pot via the CBA-synthesis module and gluconic acid-supply module. The metabolic fluxes of this artificial biosystem were strengthened using design-build-test-analysis strategy, which involved exquisite pathway design, meticulous enzyme selection, module validation and integration, and optimization of the key enzyme dosage. Under the optimized conditions, a remarkable concentration of 6.2 g/L CBA was achieved from initial 10 g/L maltodextrin with a starch-to-CBA molar conversion rate of 60 %. Taking into account that the biosystem simultaneously accumulated 3.6 g/L of gluconic acid, the maltodextrin utilization rate was calculated to be 93.3 %. Furthermore, a straightforward scaling-up process was performed to evaluate the industrial potential of this enzymatic biosystem, resulting in a yield of 21.2 g/L CBA from 50 g/L maltodextrin. This study presents an artificial ivSEBS for sustainable production of CBA from inexpensive starch, demonstrating an alternative paradigm for biomanufacturing of other aldobionic acids.

Increased DNA methylation of the splicing regulator SR45 suppresses seed abortion in litchi.

The gene regulatory networks that govern seed development are complex, yet very little is known about the genes and processes that are controlled by DNA methylation. Here, we performed single-base resolution DNA methylome analysis and found that CHH methylation increased significantly throughout seed development in litchi. Based on the association analysis of differentially methylated regions and weighted gene co-expression network analysis (WGCNA), 46 genes were identified as essential DNA methylation-regulated candidate genes involved in litchi seed development, including LcSR45, a homolog of the serine/arginine-rich (SR) splicing regulator SR45. LcSR45 is predominately expressed in the funicle, embryo, and seed integument, and displayed increased CHH methylation in the promoter during seed development. Notably, silencing of LcSR45 in a seed-aborted litchi cultivar significantly improved normal seed development, whereas the ectopic expression of LcSR45 in Arabidopsis caused seed abortion. Furthermore, LcSR45-dependent alternative splicing events were found to regulate genes involved in seed development. Together, our findings demonstrate that LcSR45 is hypermethylated, and plays a detrimental role in litchi seed development, indicating a global increase in DNA methylation at this stage.

Polydopamine-Modified 2D Iron (II) Immobilized MnPS3 Nanosheets for Multimodal Imaging-Guided Cancer Synergistic Photothermal-Chemodynamic Therapy.

Manganese phosphosulphide (MnPS3 ), a newly emerged and promising member of the 2D metal phosphorus trichalcogenides (MPX3 ) family, has aroused abundant interest due to its unique physicochemical properties and applications in energy storage and conversion. However, its potential in the field of biomedicine, particularly as a nanotherapeutic platform for cancer therapy, has remained largely unexplored. Herein, a 2D "all-in-one" theranostic nanoplatform based on MnPS3 is designed and applied for imaging-guided synergistic photothermal-chemodynamic therapy. (Iron) Fe (II) ions are immobilized on the surface of MnPS3 nanosheets to facilitate effective chemodynamic therapy (CDT). Upon surface modification with polydopamine (PDA) and polyethylene glycol (PEG), the obtained Fe-MnPS3 /PDA-PEG nanosheets exhibit exceptional photothermal conversion efficiency (η = 40.7%) and proficient pH/NIR-responsive Fenton catalytic activity, enabling efficient photothermal therapy (PTT) and CDT. Importantly, such nanoplatform can also serve as an efficient theranostic agent for multimodal imaging, facilitating real-time monitoring and guidance of the therapeutic process. After fulfilling the therapeutic functions, the Fe-MnPS3 /PDA-PEG nanosheets can be efficiently excreted from the body, alleviating the concerns of long-term retention and potential toxicity. This work presents an effective, precise, and safe 2D "all-in-one" theranostic nanoplatform based on MnPS3 for high-efficiency tumor-specific theranostics.

FK866 inhibits colorectal cancer metastasis by reducing NAD+ levels in cancer-associated fibroblasts.

BACKGROUND: Extraintestinal metastasis is the main therapeutic challenge for colorectal cancer, the third most common cancer worldwide. Various components of the tumor microenvironment, especially cancer-associated fibroblasts (CAFs), play important roles in tumor metastasis. NAMPT is often overexpressed in tumor tissues and is associated with poorer prognosis. However, the specific roles of NAMPT as well as NAD+ in tumor metastasis are relatively unknown. Therefore, we investigated the role of NAMPT and related NAD+ metabolism in cancer-associated fibroblasts mediated colorectal cancer metastasis. OBJECTIVE: This study sought to explore the molecular mechanism of FK866 in CAFs cell and colorectal cancer proliferation and metastasis. METHODS: The expression of NAMPT in clinical tissues were detected by immunohistochemically analysis. To investigate the role of NAMPT and NAD+ in the interactions between cancer cells and cancer-associated fibroblasts in tumor microenvironment, we isolated CAFs from normal and cancer tissues of clinical colorectal cancer patients. CAFs were treated with different concentrations of FK866, inhibitor of NAMPT, then the NAD+ content was detected using kits, the expression of CAFs activity and stemness indexes was assessed by Western blot and immunofluorescence. The secreted factors of these cells were analyzed by cellular inflammatory factor microarrays. The migration of SW480 after co-cultured with FK866-treated CAFs was detected by Transwell. Finally, high-throughput sequencing was performed to identify the proteins that are associated with the effect of altered NAD+ in CAFs on the migration of cancer cells. RESULTS: NAMPT expression is significantly higher in colorectal cancer tissues, especially in metastatic cancer patients, than that in normal tissues. Inhibition of NAMPT by FK866 in CAFs decreases the expression of activity indicators (α-SMA, PDGFRß), stemness indicators (BMI-1, OCT4), inflammatory factors and chemokines. Meanwhile, FK866 treatment inhibits the migration ability of SW480 cells co-cultured with CAFs. Finally, high-throughput sequencing reveals that PITX3 are down-regulated after NAD+ reduction in CAFs, which could be reversed by adding NAM, a raw material for NAD+ synthesis. CONCLUSION: Inhibition of the NAMPT-mediated NAD+ synthesis by FK866 may decrease the activation and stemness of CAFs, reduce the secretion of inflammatory and chemokines by suppressing the expression of PITX3, resulting in the suppression of colorectal cancer metastasis.

Niobium Diselenide Nanosheets: An Emerging Biodegradable Nanoplatform for Efficient Cancer Phototheranostics in the NIR-II Window.

As a prominent class of 2D transition metal dichalcogenides (TMDCs), niobium diselenide nanosheets (NbSe2 NSs) have garnered tremendous interest on account of promising applications pertaining to optoelectronics and energy storage. Although NbSe2 NSs have many unique advantages such as inherent biocompatibility and broad absorption in the NIR region, their biomedical applications have rarely been reported, especially as therapeutic agents for the second near-infrared (NIR-II) range. Herein, a biodegradable nanotherapeutic platform consisting of NbSe2 NSs is designed and demonstrated for NIR-II light-triggered photothermal therapy. NbSe2 NSs synthesized by grinding and liquid exfoliation exhibit superior photothermal conversion efficiency (48.3%) and remarkable photothermal stability in the NIR-II region. In vitro assessment demonstrates that NbSe2 NSs have favorable photothermal cell ablation efficiency and biocompatibility. After intravenous injection in vivo, the NbSe2 NSs accumulate passively in tumor sites to facilitate fluorescence imaging and tumor ablation by NIR-II illumination. Furthermore, as a result of gradual degradation in the physiological environment, NbSe2 NSs can be excreted from the body to avoid potential toxicity caused by long-term retention in vivo. The results reveal a promising NIR-II light-triggered PTT strategy with the aid of NbSe2 NSs and the platform is expected to have large potential in cancer theranostics.

Moxidectin induces autophagy arrest in colorectal cancer.

Colorectal cancer (CRC) is a cancer with a high morbidity and mortality worldwide. Hence, developing new therapeutic drugs for CRC is very important. Moxidectin (MOX) has shown good anti-glioblastoma effect both in vitro and in vivo. This study aimed to elucidate the anti-CRC effect of MOX and its potential mechanism by investigating the influence of MOX on the viability, apoptosis, necrosis and autophagy of colorectal cancer cells (HCT15 and SW620) and its underlying mechanisms. It was found that MOX can induce autophagy arrest, promote autophagy initiation, inhibit autophagic flux and cell proliferation, simultaneously PI3K-Akt-mTOR signaling pathway and microtubule acetylation. Furthermore, MOX suppressed the growth of xenograft tumors, which was consistent with the in vitro results.

Sugar Transport, Metabolism and Signaling in Fruit Development of Litchi chinensis Sonn: A Review.

Litchi chinensis Sonn. is an important evergreen fruit crop cultivated in the tropical and subtropical regions. The edible portion of litchi fruit is the aril, which contains a high concentration of sucrose, glucose, and fructose. In this study, we review various aspects of sugar transport, metabolism, and signaling during fruit development in litchi. We begin by detailing the sugar transport and accumulation during aril development, and the biosynthesis of quebrachitol as a transportable photosynthate is discussed. We then document sugar metabolism in litchi fruit. We focus on the links between sugar signaling and seed development as well as fruit abscission. Finally, we outline future directions for research on sugar metabolism and signaling to improve fruit yield and quality.

Photochemical Activity of Black Phosphorus for Near-Infrared Light Controlled In Situ Biomineralization.

The photochemical activity of black phosphorus (BP) in near-infrared (NIR) light controlled in situ biomineralization is investigated. Owing to the excellent NIR absorption, irradiation with NIR light not only promotes degradation of BP into PO4 3-, but also enhances the chemical activity to accelerate the reaction between PO4 3- and Ca2+ and promote in situ biomineralization. Mineralization of hydrogels is demonstrated by the preparation of BP incorporated hydrogel (BP@Hydrogel) which delivers greatly improved biomineralization performance under NIR illumination. The biomineralization process which can be controlled by modulating the light irradiation time and location has a high potential in controlling the mechanical properties and osteoinductive ability in tissue engineering. This study also provides insights into the degradation, photochemical activity, and new biological/biomedical applications of BP.

Biodegradable Bi2 O2 Se Quantum Dots for Photoacoustic Imaging-Guided Cancer Photothermal Therapy.

As new 2D layered nanomaterials, Bi2 O2 Se nanoplates have unique semiconducting properties that can benefit biomedical applications. Herein, a facile top-down approach for the synthesis of Bi2 O2 Se quantum dots (QDs) in a solution is described. The Bi2 O2 Se QDs with a size of 3.8 nm and thickness of 1.9 nm exhibit a high photothermal conversion coefficient of 35.7% and good photothermal stability. In vitro and in vivo assessments demonstrate that the Bi2 O2 Se QDs possess excellent photoacoustic (PA) performance and photothermal therapy (PTT) efficiency. After systemic administration, the Bi2 O2 Se QDs accumulate passively in tumors enabling efficient PA imaging of the entire tumors to facilitate imaging-guided PTT without obvious toxicity. Furthermore, the Bi2 O2 Se QDs which exhibit degradability in aqueous media not only have sufficient stability during in vivo circulation to perform the designed therapeutic functions, but also can be discharged harmlessly from the body afterward. The results reveal the great potential of Bi2 O2 Se QDs as a biodegradable multifunctional agent in medical applications.

Genome-wide identification and expression analysis of SWEET gene family in Litchi chinensis reveal the involvement of LcSWEET2a/3b in early seed development.

BACKGROUND: SWEETs (Sugar Will Eventually be Exported transporters) function as sugar efflux transporters that perform diverse physiological functions, including phloem loading, nectar secretion, seed filling, and pathogen nutrition. The SWEET gene family has been identified and characterized in a number of plant species, but little is known about in Litchi chinensis, which is an important evergreen fruit crop. RESULTS: In this study, 16 LcSWEET genes were identified and nominated according to its homologous genes in Arabidopsis and grapevine. Multiple sequence alignment showed that the 7 alpha-helical transmembrane domains (7-TMs) were basically conserved in LcSWEETs. The LcSWEETs were divided into four clades (Clade I to Clade IV) by phylogenetic tree analysis. A total of 8 predicted motifs were detected in the litchi LcSWEET genes. The 16 LcSWEET genes were unevenly distributed in 9 chromosomes and there was one pairs of segmental duplicated events by synteny analysis. The expression patterns of the 16 LcSWEET genes showed higher expression levels in reproductive organs. The temporal and spatial expression patterns of LcSWEET2a and LcSWEET3b indicated they play central roles during early seed development. CONCLUSIONS: The litchi genome contained 16 SWEET genes, and most of the genes were expressed in different tissues. Gene expression suggested that LcSWEETs played important roles in the growth and development of litchi fruits. Genes that regulate early seed development were preliminarily identified. This work provides a comprehensive understanding of the SWEET gene family in litchi, laying a strong foundation for further functional studies of LcSWEET genes and improvement of litchi fruits.

Facile mass production of self-supported two-dimensional transition metal oxides for catalytic applications.

We report a novel metal-corrosion route beyond traditional top-down or bottom-up strategies for the mass production of 2D TMOs with a self-supported structure. The self-supported 2D Co3O4, a typical TMO, exhibits excellent electrocatalytic activity and stability in the oxygen evolution reaction surpassing those of commercial precious metal RuO2 catalysts at high currents.

Electrostatic Self-Assembly of Ti3C2Tx MXene and Gold Nanorods as an Efficient Surface-Enhanced Raman Scattering Platform for Reliable and High-Sensitivity Determination of Organic Pollutants.

A reliable surface-enhanced Raman scattering (SERS) substrate composed of two-dimensional (2D) MXene (Ti3C2Tx) nanosheets and gold nanorods (AuNRs) is designed and fabricated for sensitive detection of organic pollutants. The AuNRs are uniformly distributed on the surface of the 2D MXene nanosheets because of the strong electrostatic interactions, forming abundant SERS hot spots. The MXene/AuNR SERS substrate exhibits high sensitivity and excellent reproducibility in the determination of common organic dyes such as rhodamine 6G, crystal violet, and malachite green. The detection limits are 1 × 10-12, 1 × 10-12, and 1 × 10-10 M, and relative standard deviations determined from 13 areas on each sample are 18.1, 10.1, and 15.6%, respectively. In the determination of more complex organic pesticides and pollutants, the substrate also shows excellent sensitivity and quantitative detection, and the detection limits for thiram and diquat of 1 × 10-10 and 1 × 10-8 M, respectively, are much lower than the contaminant levels stipulated by the US Environmental Protection Agency. The MXene/AuNR composite constitutes an efficient SERS platform for reliable and high-sensitivity environmental analysis and food safety monitoring.

Near-infrared light-triggered drug delivery system based on black phosphorus for in vivo bone regeneration.

A near-infrared (NIR) light-triggered drug delivery platform is produced by incorporating SrCl2 and BP nanosheets (BPs) into poly(lactic-co-glycolic acid) (PLGA) for bone regeneration. The fabricated BP-SrCl2/PLGA microspheres show efficient NIR absorption and photothermal effects due to the BPs. The NIR-triggered release behavior of Sr2+ by flawing the PLGA shells is investigated and the microspheres exhibit excellent cell viability and biodegradability. Implantation of the BP-SrCl2/PLGA microspheres into a rat femoral defect demonstrates good tissue compatibility and excellent bone regeneration capacity under NIR light irradiation. Our study indicates that local release of Sr2+ at optimal time periods controlled by NIR irradiation improves bone regeneration significantly and this NIR-triggered drug delivery system composed of BPs is suitable for therapies requiring precise control at specific time.

Black-Phosphorus-Incorporated Hydrogel as a Sprayable and Biodegradable Photothermal Platform for Postsurgical Treatment of Cancer.

Photothermal therapy (PTT) is a fledgling therapeutic strategy for cancer treatment with minimal invasiveness but clinical adoption has been stifled by concerns such as insufficient biodegradability of the PTT agents and lack of an efficient delivery system. Here, black phosphorus (BP) nanosheets are incorporated with a thermosensitive hydrogel [poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA: PLEL)] to produce a new PTT system for postoperative treatment of cancer. The BP@PLEL hydrogel exhibits excellent near infrared (NIR) photothermal performance and a rapid NIR-induced sol-gel transition as well as good biodegradability and biocompatibility in vitro and in vivo. Based on these merits, an in vivo PTT postoperative treatment strategy is established. Under NIR irradiation, the sprayed BP@PLEL hydrogel enables rapid gelation forming a gelled membrane on wounds and offers high PTT efficacy to eliminate residual tumor tissues after tumor removal surgery. Furthermore, the good photothermal antibacterial performance prevents infection and this efficient and biodegradable PTT system is very promising in postoperative treatment of cancer.

Biodegradable near-infrared-photoresponsive shape memory implants based on black phosphorus nanofillers.

In this paper, we propose a new shape memory polymer (SMP) composite with excellent near-infrared (NIR)-photoresponsive shape memory performance and biodegradability. The composite is fabricated by using piperazine-based polyurethane (PU) as thermo-responsive SMP incorporated with black-phosphorus (BP) sheets as NIR photothermal nanofillers. Under 808 nm light irradiation, the incorporated BP sheets with concentration of only 0.08 wt% enable rapid temperature increase over the glass temperature of PU and trigger the shape change of the composite with shape recovery rate of ∼100%. The in vitro and in vivo toxicity examinations demonstrate the good biocompatibility of the PU/BP composite, and it degrades naturally into non-toxic carbon dioxide and water from PU and non-toxic phosphate from BP. By implanting PU/BP columns into back subcutis and vagina of mice, they exhibit excellent shape memory activity to change their shape quickly under moderate 808 nm light irradiaiton. Such SMP composite enable the development of intelligent implantable devices, which can be easily controlled by the remote NIR light and degrade gradually after performing the designed functions in the body.