SIDERITE: Unveiling hidden siderophore diversity in the chemical space through digital exploration.

In this work, we introduced a siderophore information database (SIDERTE), a digitized siderophore information database containing 649 unique structures. Leveraging this digitalized data set, we gained a systematic overview of siderophores by their clustering patterns in the chemical space. Building upon this, we developed a functional group-based method for predicting new iron-binding molecules with experimental validation. Expanding our approach to the collection of open natural products (COCONUT) database, we predicted a staggering 3199 siderophore candidates, showcasing remarkable structure diversity that is largely unexplored. Our study provides a valuable resource for accelerating the discovery of novel iron-binding molecules and advancing our understanding of siderophores.

Effects of rearing systems (cage versus floor) on the microbial composition and transcriptome of goose ileum.

There is a gradual transition from water to dryland rearing of geese. In this study, we performed 16S rRNA sequencing (16S rRNA-seq) and transcriptome sequencing (RNA-seq) to reveal the effects of cage rearing (CR) and floor rearing (FR) systems on the microbial composition and transcriptome of the goose ileum. Through 16S rRNA-seq, Linear Discriminant Analysis Effect Size (LEfSe) analysis identified 2 (hgcI_clade and Faecalibacterium) and 14 (Bacteroides, Proteiniphilum, Proteiniclasticum, etc.) differential microbiota in CR and FR, respectively. The rearing system influenced 4 pathways including biosynthesis of amino acids in ileal microbiota. Moreover, we identified 1,198 differentially expressed genes (DEGs) in the ileum mucosa, with 957 genes up-regulated in CR and 241 genes up-regulated in FR. In CR, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the significant enrichment (p < 0.05) of 28 KEGG pathways, most of which were associated with amino acid metabolism. In FR, up-regulated DEGs were mainly enriched in KEGG pathways associated with cellular processes, including apoptosis, necroptosis, and cellular senescence. Spearman correlation analysis of differential microbiota and amino acid metabolism-related DEGs in CR showed a significant positive correlation. Additionally, differential microbiota of FR, Phascolarctobacterium and Sutterella, were positively correlated with FGF10 (p < 0.05) and PIK3R1 (p < 0.01), respectively. In conclusion, there might be differences in ileal amino acid metabolism levels between CR and FR geese, and the observed increase in harmful bacterial species in FR might impact the activity of ileal cells.

Effects of chlorophyll fluorescence on environment and gross primary productivity of moso bamboo during the leaf-expansion stage.

Chlorophyll fluorescence is the long-wave light released by the residual energy absorbed by vegetation after photosynthesis and dissipation, which can directly and non-destructively reflect the photosynthetic state of plants from the perspective of the mechanism of photosynthetic process. Moso bamboo has a substantial carbon sequestration ability, and leaf-expansion stage is an important phenological period for carbon sequestration. Gross primary production (GPP) is a key parameter reflecting vegetation carbon sequestration process. However, the ability of chlorophyll fluorescence in moso bamboo to explain GPP changes is unclear. The research area of this study is located in the bamboo forest near the flux station of Anji County, Zhejiang Province, where an observation tower is built to monitor the carbon flux and meteorological change of bamboo forest. The chlorophyll fluorescence physiological parameters (Fp) and fluorescence yield (Fy) indices were measured and calculated for the leaves of newborn moso bamboo (I Du bamboo) and the old leaves of 4- to 5-year-old moso bamboo (Ⅲ Du bamboo) during the leaf-expansion stage. The chlorophyll fluorescence in response to the environment and its effect on carbon flux were analyzed. The results showed that: Fv/Fm, Y(II) and α of Ⅰ Du bamboo gradually increased, while Ⅲ Du bamboo gradually decreased, and FYint and FY687/FY738 of Ⅰ Du bamboo were higher than those of Ⅲ Du bamboo; moso bamboo was sensitive to changes in air temperature(Ta), relative humidity(RH), water vapor pressure(E), soil temperature(ST) and soil water content (SWC), the Fy indices of the upper, middle and lower layers were significantly correlated with Ta, E and ST; single or multiple vegetation indices were able to estimate the fluorescence yield indices well (all with R2 greater than 0.77); chlorophyll fluorescence (Fp and Fy indices) of Ⅰ Du bamboo and Ⅲ Du bamboo could explain 74.4% and 72.7% of the GPP variation, respectively; chlorophyll fluorescence and normalized differential vegetation index of the canopy (NDVIc) could estimate GPP well using random forest (Ⅰ Du bamboo: r = 0.929, RMSE = 0.069 g C·m-2; Ⅲ Du bamboo: r = 0.899, RMSE = 0.134 g C·m-2). The results of this study show that chlorophyll fluorescence can provide a basis for judging the response of moso bamboo to environmental changes and can well explain GPP. This study has important scientific significance for evaluating the potential mechanisms of growth, stress feedback and photosynthetic carbon sequestration of bamboo.

Metal-free iodination of arylaldehydes for total synthesis of aristogins A-F and hernandial.

Iodine is one of the most effective sources for iodination of aromatic compounds; however, its electrophilicity is insufficient for direct iodination. The selection of appropriate environmentally friendly and cost-effective oxidants in combination with iodine for the iodination of aromatic rings, along with its application in the synthesis of natural products, holds significant importance. A highly efficient method utilizing I(III) as the initiator has been successfully developed for monoiodination of arylaldehydes. The method demonstrates good compatibility with a wide range of (hetero)aromatic aldehydes, resulting in moderate to excellent yields, without the need for any toxic, volatile or explosive reagents. The synthesis of seven natural products, namely aristogins A-F and hernandial, was achieved through this iodination followed by Ullmann-type coupling.

ESKtides: a comprehensive database and mining method for ESKAPE phage-derived antimicrobial peptides.

'Superbugs' have received increasing attention from researchers, such as ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.), which directly led to about 1 270 000 death cases in 2019. Recently, phage peptidoglycan hydrolases (PGHs)-derived antimicrobial peptides were proposed as new antibacterial agents against multidrug-resistant bacteria. However, there is still a lack of methods for mining antimicrobial peptides based on phages or phage PGHs. Here, by using a collection of 6809 genomes of ESKAPE isolates and corresponding phages in public databases, based on a unified annotation process of all the genomes, PGHs were systematically identified, from which peptides were mined. As a result, a total of 12 067 248 peptides with high antibacterial activities were respectively determined. A user-friendly tool was developed to predict the phage PGHs-derived antimicrobial peptides from customized genomes, which also allows the calculation of peptide phylogeny, physicochemical properties, and secondary structure. Finally, a user-friendly and intuitive database, ESKtides (http://www.phageonehealth.cn:9000/ESKtides), was designed for data browsing, searching and downloading, which provides a rich peptide library based on ESKAPE prophages and phages. Database URL:  10.1093/database/baae022.

Postbiotics: emerging therapeutic approach in diabetic retinopathy.

Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients that poses a serious risk as it can cause substantial visual impairment and even vision loss. Due to the prolonged onset of DR, lengthy treatment duration, and limited therapeutic effectiveness, it is extremely important to find a new strategy for the treatment of DR. Postbiotic is an emerging dietary supplement which consists of the inactivate microbiota and its metabolites. Numerous animal experiments have demonstrated that intervention with postbiotics reduces hyperglycemia, attenuates retinal peripapillary and endothelial cell damage, improves retinal microcirculatory dysfunction, and consequently delays the progression of DR. More strikingly, unlike conventional probiotics and prebiotics, postbiotics with small molecules can directly colonize the intestinal epithelial cells, and exert heat-resistant, acid-resistant, and durable for storage. Despite few clinical significance, oral administration with postbiotics might become the effective management for the prevention and treatment of DR. In this review, we summarized the basic conception, classification, molecular mechanisms, and the advances in the therapeutic implications of postbiotics in the pathogenesis of DR. Postbiotics present great potential as a viable adjunctive therapy for DR.

Postbiotics in colorectal cancer: intervention mechanisms and perspectives.

Colorectal cancer (CRC) is a common malignancy affecting the gastrointestinal tract worldwide. The etiology and progression of CRC are related to factors such as environmental influences, dietary structure, and genetic susceptibility. Intestinal microbiota can influence the integrity of the intestinal mucosal barrier and modulate intestinal immunity by secreting various metabolites. Dysbiosis of the intestinal microbiota can affect the metabolites of the microbial, leading to the accumulation of toxic metabolites, which can trigger chronic inflammation or DNA damage and ultimately lead to cellular carcinogenesis and the development of CRC. Postbiotics are preparations of inanimate microorganisms or their components that are beneficial to the health of the host, with the main components including bacterial components (e.g., exopolysaccharides, teichoic acids, surface layer protein) and metabolites (e.g., short-chain fatty acids, tryptophan metabolite, bile acids, vitamins and enzymes). Compared with traditional probiotics, it has a more stable chemical structure and higher safety. In recent years, it has been demonstrated that postbiotics are involved in regulating intestinal microecology and improving the progression of CRC, which provides new ideas for the prevention and diagnosis of CRC. In this article, we review the changes in intestinal microbiota in different states of the gut and the mechanisms of anti-tumor activity of postbiotic-related components, and discuss the potential significance of postbiotics in the diagnosis and treatment of CRC. This reviews the changes and pathogenesis of intestinal microbiota in the development of CRC, and summarizes the relevant mechanisms of postbiotics in resisting the development of CRC in recent years, as well as the advantages and limitations of postbiotics in the treatment process of CRC.

Full phenology cycle carbon flux dynamics and driving mechanism of Moso bamboo forest.

Introduction: Moso bamboo forests, widely distributed in subtropical regions, are increasingly valued for their strong carbon sequestration capacity. However, the carbon flux variations and the driving mechanisms of Moso bamboo forest ecosystems of each phenology period have not been adequately explained. Methods: Hence, this study utilizes comprehensive observational data from a Moso bamboo forest eddy covariance observation for the full phenological cycle (2011-2015), fitting a light response equation to elucidate the evolving dynamics of carbon fluxes and photosynthetic characteristics throughout the entire phenological cycle, and employing correlation and path analysis to reveal the response mechanisms of carbon fluxes to both biotic and abiotic factors. Results: The results showed that, First, the net ecosystem exchange (NEE) of Moso bamboo forest exhibits significant variations across six phenological periods, with LSOFF demonstrating the highest NEE at -23.85 ± 12.61 gC·m-2·5day-1, followed by LSON at -19.04 ± 11.77 gC·m-2·5day-1 and FGON at -17.30 ± 9.58 gC·m-2·5day-1, while NFOFF have the lowest value with 3.37 ± 8.24 gC·m-2·5day-1. Second, the maximum net photosynthetic rate (Pmax) and apparent quantum efficiency (α) fluctuated from 0.42 ± 0.20 (FGON) to 0.75 ± 0.24 mg·m-2·s-1 (NFOFF) and from 2.3 ± 1.3 (NFOFF) to 3.3 ± 1.8 µg·µmol-1 (LSOFF), respectively. Third, based on the path analysis, soil temperature was the most important driving factor of photosynthetic rate and NEE variation, with path coefficient 0.81 and 0.55, respectively, followed by leaf area index (LAI), air temperature, and vapor pressure difference, and precipitation. Finally, interannually, increased LAI demonstrated the potential to enhance the carbon sequestration capability of Moso bamboo forests, particularly in off-years, with the highest correlation coefficient with NEE (-0.59) among the six factors. Discussion: The results provide a scientific basis for carbon sink assessment of Moso bamboo forests and provide a reference for developing Moso bamboo forest management strategies.

Bubble-Mediated Production of Few-Layer Graphene via Vapor-Liquid Reaction between Carbon Dioxide and Magnesium Melt.

It is urgent to develop novel technologies to convert carbon dioxide to graphene. In this work, a bubble-mediated approach via a chemical reaction between carbon dioxide gas and magnesium melt to fabricate a few-layer graphene was illustrated. The morphology and defects of graphene can be regulated by manipulating the melt temperature. The preparation of graphene at 720 °C exhibited an excellent quality of surface and graphitization degree. The high-quality few-layer graphene can be grown under the combined effect of carbon dioxide bubbles and in-situ grown MgO. This preparation method possesses the advantages of high efficiency, low cost, and environmental protection, which may provide a new strategy for the recovery and reuse of greenhouse gases.

RPL35A promotes the progression of cholangiocarcinoma by mediating HSPA8 ubiquitination.

BACKGROUND: Cholangiocarcinoma (CCA) is a biliary epithelial malignant tumor with an increasing incidence worldwide. Therefore, further understanding of the molecular mechanisms of CCA progression is required to identify new therapeutic targets. METHODS: The expression of RPL35A in CCA and para-carcinoma tissues was detected by immunohistochemical staining. IP-MS combined with Co-IP identified downstream proteins regulated by RPL35A. Western blot and Co-IP of CHX or MG-132 treated CCA cells were used to verify the regulation of HSPA8 protein by RPL35A. Cell experiments and subcutaneous tumorigenesis experiments in nude mice were performed to evaluate the effects of RPL35A and HSPA8 on the proliferation, apoptosis, cell cycle, migration of CCA cells and tumor growth in vivo. RESULTS: RPL35A was significantly upregulated in CCA tissues and cells. RPL35A knockdown inhibited the proliferation and migration of HCCC-9810 and HUCCT1 cells, induced apoptosis, and arrested the cell cycle in G1 phase. HSPA8 was a downstream protein of RPL35A and overexpressed in CCA. RPL35A knockdown impaired HSPA8 protein stability and increased HSPA8 protein ubiquitination levels. RPL35A overexpression promoted CCA cell proliferation and migration. HSPA8 knockdown inhibited CCA cell proliferation and migration, and reversed the promoting effect of RPL35A. Furthermore, RPL35A promoted tumor growth in vivo. In contrast, HSPA8 knockdown suppressed tumor growth, while was able to restore the effects of RPL35A overexpression. CONCLUSION: RPL35A was upregulated in CCA tissues and promoted the progression of CCA by mediating HSPA8 ubiquitination.

Spatiotemporal patterns of net primary productivity of subtropical forests in China and its response to drought.

Net primary productivity (NPP) is an important indicator used to evaluate the carbon sequestration capacity of forest ecosystems. Subtropical forest ecosystems play an indispensable role in maintaining the global carbon balance, while frequently occurring drought events in recent years have seriously damaged their productivity. However, the spatiotemporal patterns of NPP, as well as its response to drought, remain uncertain. In this study, the multiscale drought characteristics in subtropical China during 1981-2015 were analyzed based on the standardized precipitation evapotranspiration index. Then, simulated and analyzed the spatiotemporal NPP of subtropical forests by the boreal ecosystem productivity simulator model. Finally, the response of NPP to drought was analyzed based on multiple statistical indices. The results show that most regions in subtropical China experienced mild and moderate drought during 1981-2015. In particular, the extent of drought severity has shown a noticeable increasing trend after 2000. The forest NPP ranged from 622.64 to 1323.82 gC·m-2·a-1, with an overall increase rate of 16.15 gC·m-2·a-1; in particular, the contribution of the western forest NPP became increasingly important. Drought stress has limited the growth of subtropical forest NPP in China, with summer and wet season time scales of drought having the greatest impact on forest NPP anomalies, followed by autumn time scales. The limitation is mostly because the drought duration continually increased, leading to differences in the impact of drought on forest NPP before and after 2000, with declines of 59.55 % and 82.45 %, respectively, mainly concentrated in southwestern regions, such as Yunnan, Guangxi, and Sichuan provinces. This study quantitatively analyzed the impact of drought on subtropical forest NPP, and provides scientific basis for subtropical forest response and adaptation to climate change.

Pathogens and antibiotic resistance genes during the landfill leachate treatment process: Occurrence, fate, and impact on groundwater.

Landfill leachate is an essential source of pathogens and antibiotic resistance genes (ARGs) in the environment. However, information on the removal behavior of pathogens and ARGs during the leachate treatment and the impact on surrounding groundwater is limited. In this study, we investigated the effects of leachate treatment on the removal of pathogens and ARGs with metagenomic sequencing, as well as the impact of landfill effluent on groundwater. It is shown that the leachate treatment could not completely remove pathogens and ARGs. Twenty-nine additional pathogens and twenty-nine ARGs were newly identified in the landfill effluent. The relative abundance of pathogens and multiple antibiotic resistance genes decreased after ultrafiltration but relative abundance increased after reverse osmosis. In addition, the relative abundances of Acinetobacter baumannii, Erwinia amylovora, Escherichia coli, Fusarium graminearum, Klebsiella pneumoniae, and Magnaporthe oryzae, as well as mdtH, VanZ, and blaOXA-53 increased significantly in the landfill effluent compared to the untreated leachate. The relative abundance of some mobile genetic elements (tniA, tniB, tnpA, istA, IS91) in leachate also increased after ultrafiltration and reverse osmosis. The size of pathogens, the size and properties of ARGs and mobile genetic elements, and the materials of ultrafiltration and reverse osmosis membranes may affect the removal effect of pathogens, ARGs and mobile genetic elements in leachate treatment process. Interestingly, the pathogens and ARGs in landfill effluent were transferred to groundwater according to SourceTracker. The ARGs, mobile genetic elements, and pathogens that are difficult to remove in the leachate treatment process, provide a reference for optimizing the leachate treatment process and improving the control of pathogens and ARGs. Furthermore, this study clarifies the effect of landfill leachate sources of pathogens and ARGs in groundwater.

Preparation of the Levo-Tetrahydropalmatine Liposome Gel and Its Transdermal Study.

Purpose: The aim of this study was to develop a liposome gel containing levo-tetrahydropalmatine (l-THP) and evaluate its transdermal properties. Methods: A L16 (43) orthogonal experiment was conducted to optimize the preparation of l-THP liposomes and assess their characterization and stability in a gel. The transdermal features were analyzed through in vivo and in vitro experiments on rats and Strat-M® membrane, respectively. The metabolism of l-THP in liver and skin S9 fractions was also studied. Results: The optimization of the orthogonal experiment revealed that the ideal mass ratio of phosphatidylcholine, cholesterol, and l-THP during preparation was 10:1:3. The resulting liposome exhibited a particle size of 68 nm, a PDI of 0.27, a drug loading of 4.33%, an encapsulation of 18.79%, and a zeta potential of -41.27 mV. Both the l-THP and its liposome-gel formulation were found to be stable for a duration of 45 days at 4 °C and 30 °C. During the in vivo transdermal study, the maximum concentration (Cmax) of l-THP from the liposome gel was 0.16 µg/mL, and the time to reach this maximum concentration (tmax) was 1.2 hours. The relative bioavailability of l-THP in the liposome gel was 233.8% compared to the emulsion. The concentration of l-THP (prepared in PBS) decreased at a rate of 0.0067 µg/mL/min in the liver S9 fraction and 0.0027 µg/mL/min in the skin S9 fraction, however, this difference was not observed when l-THP was encapsulated in liposomes. l-THP passed through the Strat-M® membrane at a rate of 0.0032 mg/cm2/h and 0.002 mg/cm2/h for the emulsion and liposome gel, respectively. Conclusion: The optimal process for the preparation of l-THP liposomes was obtained. Compared to the emulsion, the liposomes provided greater bioavailability when used transdermally. The liposomes also provided greater stability for l-THP during storage.

Survival benefit of perioperative locoregional adjuvant treatment for hepatocellular carcinoma with portal vein tumor thrombosis: A systematic review and Bayesian network meta-analysis.

BACKGROUND: To identify the optimal strategy for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) by comparing the oncological prognosis of different perioperative locoregional adjuvant treatments. METHODS: Electronic database were searched for relevant studies. Overall survival (OS) and recurrence-free survival (RFS) were pooled by pairwise and network meta-analysis. RESULTS: Fourteen eligible trials with 1927 patients and covering four adjuvant treatments were included. All adjuvant therapies in combination with surgery were shown to be superior to surgery alone. Adjuvant therapy with radiotherapy had the lowest hazard ratio (HR) for both OS (HR: 0.38, 95% CrI: 0.25-0.57) and RFS (HR: 0.27, 95% CrI: 0.11-0.65) compared with other combination treatments, with estimated surface under the cumulative ranking of 93.2% and 82.7%, respectively. CONCLUSIONS: Perioperative locoregional adjuvant therapy provides OS benefits and reduces the risk of recurrence for patients suffering from HCC with PVTT. Radiotherapy is likely to be the most effective adjuvant regimen.

LGALS1 regulates cell adhesion to promote the progression of ovarian cancer.

The present study aimed to explore the significance and molecular mechanisms of galectin-1 (LGALS1) in ovarian cancer (OC). Using the Gene Expression Omnibus database and The Cancer Genome Atlas database, the results of the present study demonstrated that LGALS1 mRNA expression was markedly increased in OC and associated with advanced tumor, lymphatic metastasis and residual lesions. In Kaplan-Meier analysis, patients who expressed LGALS1 highly had a poor prognosis. Furthermore, using The Cancer Genome Atlas database, differentially expressed genes that are potentially regulated by LGALS1 in OC were determined. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to build a biological network of upregulated differentially expressed genes. The results of the enrichment analysis revealed that the upregulated differentially expressed genes were primarily associated with 'ECM-receptor interaction', 'cell-matrix adhesion' and 'focal adhesion', which are closely associated with the metastasis of cancer cells. Subsequently, cell adhesion was selected for further analysis. The results demonstrated that LGALS1 was co-expressed with the candidate genes. Subsequently, the elevated expression levels of candidate genes were verified in OC tissues, and survival analysis indicated that high expression of candidate genes was associated with shortened overall survival of patients with OC. In the present study, OC samples were also collected to verify the high protein expression levels of LGALS1 and fibronectin 1. The results of the present study highlighted that LGALS1 may regulate cell adhesion and participate in the development of OC. Therefore, LGALS1 exhibits potential as a therapeutic target in OC.

Exploring right ovary degeneration in duck and goose embryos by histology and transcriptome dynamics analysis.

BACKGROUND: The development of asymmetric chick gonads involves separate developmental programs in the left and right gonads. In contrast to the left ovary developing into a fully functional reproductive organ, the right ovary undergoes gradual degeneration. However, the molecular mechanisms underlying the the degeneration of the right ovary remain incompletely understood. In the present study, we investigated the histomorphological and transcriptomic changes in the right ovary of ducks and geese during the the embryonic stage up to post-hatching day 1. RESULT: Hematoxylin-eosin stainings revealed that the right ovary developed until embryonic day 20 in ducks (DE20) or embryonic day 22 in geese (GE22), after which it started to regress. Further RNA-seq analyses revealed that both the differentially expressed genes (DEGs) in ducks and geese right ovary developmental stage were significantly enriched in cell adhesion-related pathway (ECM-receptor interaction, Focal adhesion pathway) and Cellular senescence pathway. Then during the degeneration stage, the DEGs were primarily enriched in pathways associated with inflammation, including Herpes simplex virus 1 infection, Influenza A, and Toll-like receptor signaling pathway. Moreover, duck-specific DEGs showed enrichment in Steroid hormone biosynthesis, Base excision repair, and the Wnt signaling pathway, while geese-specifically DEGs were found to be enriched in apoptosis and inflammation-related pathways, such as Ferroptosis, Necroptosis, RIG-I-like receptor signaling pathway, and NOD-like receptor signaling pathway. These findings suggest that the degeneration process of the right ovary in ducks occurs at a slower pace compared to that in geese. Additionally, the observation of the left ovary of the geese varying degeneration rates in the right ovary after hatching indicated that the development of the left ovary may be influenced by the degeneration of the right ovary. CONCLUSION: The data presented in this study provide valuable insights into the dynamic changes in histological structure and transcriptome during the degeneration of the right ovary in ducks and geese. In addition, through the analysis of shared characteristics in the degeneration process of the right ovary in both ducks and geese, we have uncovered the patterns of degradation and elucidated the molecular mechanisms involved in the regression of the right ovary in poultry. Furthermore, we have also made initial discoveries regarding the relationship between the degeneration of the right ovary and the development of the left ovary.

Mature cystic teratoma of the ovary with a grossly visible, completely developed intestinal loop: A case report and review of the literature.

RATIONALE: The mature cystic teratoma of the ovary (MCTO), is composed of mature differentiated elements, thus showing highly differentiated tissue and highly morphological heterogeneity. Although gastrointestinal epithelium can be identified in 7% to 13% of cases of MCTO, the occurrence of visible, functional, and fully developed loop tissue is rare in clinical practice. PATIENT CONCERNS: A 17-year-old female patient presented with persistent abdominal pain. DIAGNOSIS: The patient was diagnosed with MCTO where a visible, functional intestinal loop was observed during laparoscopic surgery. Microscopy of the intestinal structure indicated a well-organized, intact layer of intestinal wall. INTERVENTIONS: An emergency single-port laparoscopic excision of the right ovarian cyst and histopathology were performed. OUTCOMES: After 2 years of follow-up, there were no signs of recurrence in the patient. LESSONS: The immune signature of CK7-/CK20+ is characteristic of tumors of gastrointestinal origin and can be used to distinguish tumors associated with mature cystic teratoma. Besides, gynecologists should keep an eye on the possibility of malignant transformation malignant transformation of MCTO.

Rgl-exomiR-7972, a novel plant exosomal microRNA derived from fresh Rehmanniae Radix, ameliorated lipopolysaccharide-induced acute lung injury and gut dysbiosis.

Plant-derived exosome-like nanoparticles (ELNs) have been proposed as a novel therapeutic tool for preventing human diseases. However, the number of well-verified plant ELNs remains limited. In this study, the microRNAs in ELNs derived from fresh Rehmanniae Radix, a well-known traditional Chinese herb for treating inflammatory and metabolic diseases, were determined by using microRNA sequencing to investigate the active components in the ELNs and the protection against lipopolysaccharide (LPS)-induced acute lung inflammation in vivo and in vitro. The results showed that rgl-miR-7972 (miR-7972) was the main ingredient in ELNs. It exerted stronger protective activities against LPS-induced acute lung inflammation than catalpol and acteoside, which are two well-known chemical markers in this herb. Moreover, miR-7972 decreased the production of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide (NO) in LPS-exposed RAW264.7 cells, thereby facilitating M2 macrophage polarization. Mechanically, miR-7972 downregulated the expression of G protein-coupled receptor 161 (GPR161), activating the Hedgehog pathway, and inhibited the biofilm form of Escherichia coli via targeting virulence gene sxt2. Therefore, miR-7972 derived from fresh R. Radix alleviated LPS-induced lung inflammation by targeting the GPR161-mediated Hedgehog pathway, recovering gut microbiota dysbiosis. It also provided a new direction for gaining novel bioactivity nucleic acid drugs and broadening the knowledge on cross-kingdom physiological regulation through miRNAs.

Transformable nanodrugs for overcoming the biological barriers in the tumor environment during drug delivery.

Drug delivery systems have been studied massively with explosive growth in the last few decades. However, challenges such as biological barriers are still obstructing the delivery efficiency of nanomedicines. Reports have shown that the physicochemical properties, such as the morphologies of nanodrugs, could highly affect their biodistribution and bioavailability. Therefore, transformable nanodrugs that take advantage of different sizes and shapes allow for overcoming multiple biological barriers, providing promising prospects for drug delivery. This review aims to present an overview of the most recent developments of transformable nanodrugs in this emerging field. First, the design principles and transformation mechanisms which serve as guidelines for smart nanodrugs are summarized. Afterward, their applications in overcoming biological barriers, including the bloodstream, intratumoral pressure, cellular membrane, endosomal wrapping, and nuclear membrane, are highlighted. Finally, discussions on the current developments and future perspectives of transformable nanodrugs are given.

Hydrogel armed with Bmp2 mRNA-enriched exosomes enhances bone regeneration.

BACKGROUND: Sustained release of bioactive BMP2 (bone morphogenetic protein-2) is important for bone regeneration, while the intrinsic short half-life of BMP2 at protein level cannot meet the clinical need. In this study, we aimed to design Bmp2 mRNA-enriched engineered exosomes, which were then loaded into specific hydrogel to achieve sustained release for more efficient and safe bone regeneration. RESULTS: Bmp2 mRNA was enriched into exosomes by selective inhibition of translation in donor cells, in which NoBody (non-annotated P-body dissociating polypeptide, a protein that inhibits mRNA translation) and modified engineered BMP2 plasmids were co-transfected. The derived exosomes were named ExoBMP2+NoBody. In vitro experiments confirmed that ExoBMP2+NoBody had higher abundance of Bmp2 mRNA and thus stronger osteogenic induction capacity. When loaded into GelMA hydrogel via ally-L-glycine modified CP05 linker, the exosomes could be slowly released and thus ensure prolonged effect of BMP2 when endocytosed by the recipient cells. In the in vivo calvarial defect model, ExoBMP2+NoBody-loaded GelMA displayed great capacity in promoting bone regeneration. CONCLUSIONS: Together, the proposed ExoBMP2+NoBody-loaded GelMA can provide an efficient and innovative strategy for bone regeneration.