α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

Photocatalytic reduction of carbon dioxide by BiTeX (X = Cl, Br, I) under visible-light irradiation.

In this study, a series of BiTeX (X = Cl, Br, I) photocatalysts were successfully synthesized via a simple hydrothermal method. The synthesis process involved dissolving BiX3 and Te powder in toluene to identify the most efficient material for photocatalytic activity. The main objective of this approach is to facilitate the conversion of carbon dioxide into sustainable solar fuels, such as alcohols and hydrocarbons, offering an appealing solution to address environmental concerns and energy crises. The BiTeX photocatalysts demonstrated significant proficiency in converting CO2 into CH4, particularly BiTeCl exhibited a notable photocatalytic conversion rate of up to 0.51 µmolg-1h-1. The optimized BiTeX photocatalysts displayed a gradual and selective transition from CO2 to CH4, ultimately producing valuable hydrocarbons (C2+). Furthermore, owing to their ability to reduce CO2, these photocatalysts show promise as materials for mitigating environmental pollution.

Optimizing erectile function evaluation pattern in postoperative pelvic fracture-urethral injury patients: introducing PFUI pEF PROM.

PURPOSE: To establish a psychometric validated pelvic fracture-urethral injury postoperative erectile function patient reported outcome measure (PFUI pEF PROM). We also aim to explore PFUI patients' potential classification and suitable postoperative erectile function assessment pattern. METHODS: A total of 93 PFUI patients who treated by excision and primary anastomotic (EPA) urethroplasty from January 2020 to August 2022 were enrolled to this study. Patients who had intercourse completed the IIEF-5, those who had sexual stimulation other than intercourse finished PFUI pEF PROM, and those who performed both completed the IIEF-5, and PFUI pEF PROM. Erection Hardness Score (EHS) was completed by all patients. This PROM was performed psychometric validation and used to find PFUI patients potential classification through latent class analysis. Then, we determined the cut-off value though receiver-operating characteristic (ROC) curve and performed univariate analysis subgroups feature. RESULTS: The PFUI pEF PROM demonstrated high reliability and validity with a Cronbach's alpha of 0.928. It correlated significantly with IIEF-5 (r = 0.550, p < 0.001) and EHS (r = 0.909, p < 0.001). The latent class analysis identified three patient subgroups, with 14.5 as the subgroup cut-off value. Urethral stricture length, IIEF-5, and EHS score were identified as influence factors for maximal erection potential. An assessment pattern combining IIEF-5, EHS, and the PFUI pEF PROM covered 92.5% of patients. CONCLUSION: This PROM effectively addresses the current limitation in assessing erectile function in PFUI patients. This study provides a promising tool for stratified assessment, prediction erection recovery, and treatment guidance in the PFUI Erectile dysfunction field.

Effect of Spatter Behavior on Mechanical Properties and Surface Roughness of Printed Parts during PBF-LM of 316L.

The spatter generated by the interaction between laser and powder during Powder Bed Fusion-Laser Melting (PBF-LM) can significantly affect the quality of printed parts. A high-speed camera is used to observe the dynamic process of spatter's behavior under different layer thickness and laser powers during the printing process, and to analyze the printed samples' surface roughness, microstructure, and mechanical properties. In terms of spatter image processing, employing an optical flow approach to track and quantify the number of spatters efficiently eliminates statistical redundancy and improves statistical correctness. It is found that under the same laser power, the number of spatters produced by the laser scan direction with the gas flow (LSD-W) is more than that by the laser scan direction against the gas flow (LSD-A), and the number of spatters produced increases with the increase of laser power. Analyzing the mechanical properties and surface roughness of the printed samples under different process parameters quantitatively reveals that differences in the spatter amount generated under different process parameters in the PBF-LM process is not the determining factor affecting the difference in tensile strength of printed parts. During LSD-W, the number of spatters generated at laser power of 170 W and layer thickness of 0.03 mm is 87, and the tensile strength of the printed sample is 618 MPa. During LSD-W, the number of spatters generated at laser power of 320 W and layer thickness of 0.05 mm is 211, and the tensile strength of the printed sample is 680 MPa. Instead, spatter generation has a more direct impact on the surface roughness of printed parts. The layer thickness is 0.03 mm, the laser power is 170 W, and (Ra = 2.372 µm) is the surface roughness of the sample. The layer thickness is 0.05 mm, the laser power is 320 W, and (Ra = 8.163 µm) is the surface roughness of the sample.

The application value of LAVA-flex sequences in enhanced MRI scans of nasopharyngeal carcinoma: comparison with T1WI-IDEAL.

Introduction: Magnetic resonance imaging (MRI) staging scans are critical for the diagnosis and treatment of patients with nasopharyngeal cancer (NPC). We aimed to evaluate the application value of LAVA-Flex and T1WI-IDEAL sequences in MRI staging scans. Methods: Eighty-four newly diagnosed NPC patients underwent both LAVA-Flex and T1WI-IDEAL sequences during MRI examinations. Two radiologists independently scored the acquisitions of image quality, fat suppression quality, artifacts, vascular and nerve display. The obtained scores were compared using the Wilcoxon signed rank test. According to the signal intensity (SI) measurements, the uniformity of fat suppression, contrast between tumor lesions and subcutaneous fat tissue, and signal-to-noise ratio (SNR) were compared by the paired t-test. Results: Compared to the T1WI-IDEAL sequence, LAVA-Flex exhibited fewer artifacts (P<0.05), better visualization of nerves and vessels (P<0.05), and performed superior in the fat contrast ratio of the primary lesion and metastatic lymph nodes (0.80 vs. 0.52, 0.81 vs. 0.56, separately, P<0.001). There was no statistically significant difference in overall image quality, tumor signal-to-noise ratio (SNR), muscle SNR, and the detection rate of lesions between the two sequences (P>0.05). T1WI-IDEAL was superior to LAVA-Flex in the evaluation of fat suppression uniformity (P<0.05). Discussion: LAVA-Flex sequence provides satisfactory image quality and better visualization of nerves and vessels for NPC with shorter scanning times.

Dynamics of Puccinia striiformis f. sp. tritici Urediniospores and Its Relationship with Meteorological Factors in Mianyang, China.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the main diseases of wheat worldwide. Mianyang of Sichuan province in Southwest China is one of main regions for winter Pst inoculum production and spring epidemic and provides urediniospores for infecting wheat in the surrounding regions. Understanding the urediniospore dynamics is important to predict and manage stripe rust. In this study, spore trapping coupled with a TaqMan real-time quantitative PCR method was used to monitor airborne Pst urediniospores from December 2019 to December 2022 in Mianyang. Weather conditions (temperature, relative humidity, daily sunshine duration, and precipitation) were collected for the same period. These data were used to study the relationship of airborne urediniospore density with climatic conditions. The results showed that Pst urediniospores were captured all year round, and the annual peak of urediniospore densities occurred in the period from March to April in which the urediniospores accounted for the largest proportion of the annual total urediniospores. The density of urediniospores in the period of March to April was linearly related to the average sunshine duration of 20 days and average temperature of 15 days prior to the final day of a 7-day trapping period. This relationship needs to be tested in other regions where Pst can sporulate during the winter before it can be integrated with Pst infection conditions to predict rust development.

Bidirectionally promoting assembly order for ultrastiff and highly thermally conductive graphene fibres.

Macroscopic fibres assembled from two-dimensional (2D) nanosheets are new and impressing type of fibre materials besides those from one-dimensional (1D) polymers, such as graphene fibres. However, the preparation and property-enhancing technologies of these fibres follow those from 1D polymers by improving the orientation along the fibre axis, leading to non-optimized microstructures and low integrated performances. Here, we show a concept of bidirectionally promoting the assembly order, making graphene fibres achieve synergistically improved mechanical and thermal properties. Concentric arrangement of graphene oxide sheets in the cross-section and alignment along fibre axis are realized by multiple shear-flow fields, which bidirectionally promotes the sheet-order of graphene sheets in solid fibres, generates densified and crystalline graphitic structures, and produces graphene fibres with ultrahigh modulus (901 GPa) and thermal conductivity (1660 W m-1 K-1). We believe that the concept would enhance both scientific and technological cognition of the assembly process of 2D nanosheets.

In vitro and in vivo antibacterial studies of volatile oil from Atractylodis Rhizoma against Staphylococcus pseudintermedius and multidrug resistant Staphylococcus pseudintermedius strains from canine pyoderma.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodis Rhizoma is extensively employed in Traditional Chinese Medicine for the treatment of skin and gastrointestinal ailments. Its active components have been proven to demonstrate numerous beneficial properties, including antibacterial, antiviral, anti-inflammatory, anti-tumor, and anti-ulcer activities. Furthermore, the volatile oil from Atractylodis Rhizoma (VOAR) has been reported to effectively inhibit and eradicate pathogens such as Staphylococcus aureus, Escherichia coli and Candida albicans. Of particular concern is Staphylococcus pseudintermedius, the predominant pathogen responsible for canine pyoderma, whose increasing antimicrobial resistance poses a serious public health threat. VOAR merits further investigation regarding its antibacterial potential against Staphylococcus pseudintermedius. AIM OF THE STUDY: The study aims to verify the in vitro antibacterial activity of VOAR against Staphylococcus pseudintermedius. And a superficial skin infection model in mice was established to assess the in vivo therapeutic effect of VOAR. MATERIALS AND METHODS: Thirty strains of S. pseudintermedius were isolated from dogs with pyoderma, and the drug resistance was analyzed by disc diffusion method. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of VOAR were determined through the broth dilution method. The growth curve of bacteria in a culture medium containing VOAR was monitored using a UV spectrophotometer. Scanning electron microscopy was employed to observe the effects of VOAR on the microstructure of S. pseudintermedius. The impact of VOAR on the antibiotic resistance of S. pseudintermedius was assessed using the disc diffusion method. Twenty mice were randomly divided into four groups: the control group, the physiological saline group, the VOAR group, and the amikacin group. With the exception of the control group, the skin barrier of mice was disrupted by tap stripping, and the mice were subsequently inoculated with S. pseudintermedius to establish a superficial skin infection model. The modeled mice were treated with normal saline, VOAR, and amikacin for 5 days. Following the treatment period, the therapeutic effect of each group was evaluated based on the measures of body weight, skin symptoms, tissue bacterial load, tissue IL-6 content, and histopathological changes. RESULTS: The MIC and MBC of VOAR against 30 clinical isolates of S. pseudintermedius were found to be 0.005425% and 0.016875%, respectively. VOAR could exhibit the ability to delay the entry of bacteria into the logarithmic growth phase, disrupt the bacterial structure, and enhance the antibacterial zone in conjunction with antibiotic drugs. In the superficial skin infection model mice, VOAR significantly reduced the scores for skin redness (P < 0.0001), scab formation (P < 0.0001), and wrinkles (P < 0.0001). Moreover, VOAR markedly reduced the bacterial load (P < 0.001) and IL-6 content (P < 0.0001) in the skin tissues of mice. Histopathological observations revealed that the full-layer skin structure in the VOAR group was more complete, with clearer skin layers, and showed significant improvement in inflammatory cell infiltration and fibroblast proliferation compared to other groups. CONCLUSION: The results demonstrate that VOAR effectively inhibits and eradicates Staphylococcus pseudintermedius in vitro while also enhancing the pathogen's sensitivity to antibiotics. Moreover, VOAR exhibits a pronounced therapeutic effect in the superficial skin infection model mice.

Transcriptome analysis of the adenoma-carcinoma sequences identifies novel biomarkers associated with development of canine colorectal cancer.

The concept of adenoma-to-cancer transformation in human colorectal cancer (CRC) is widely accepted. However, the relationship between transcriptome features and adenoma to carcinoma transformation in canines is not clear. We collected transcriptome data from 8 normal colon tissues, 4 adenoma tissues, and 15 cancer tissues. Differential analysis was unable to determine the dynamic changes of genes but revealed that PFKFB3 may play a key role in this process. Enrichment analysis explained metabolic dysregulation, immunosuppression, and typical cancer pathways in canine colorectal tumors. MFuzz generated specific dynamic expression patterns of five differentially expressed genes (DEGs). Weighted correlation network analysis showed that DEGs in cluster 3 were associated with malignant tissues, revealing the key role of inflammatory and immune pathways in canine CRC, and the S100A protein family was also found to be involved in the malignant transformation of canine colorectal tumors. By comparing strategies between humans and dogs, we found five novel markers that may be drivers of CRC. Among them, GTBP4 showed excellent diagnostic and prognostic ability. This study was the first systematic exploration of transformation in canine CRC, complemented the molecular characteristics of the development and progression of canine CRC, and provided new potential biomarkers and comparative oncologic evidence for biomarker studies in human colorectal cancer.

Flexible in-cavity MRI receiving coil for ultra-high-resolution imaging of the pituitary gland.

OBJECTIVE: The objective of this study was the preclinical design and construction of a flexible intrasphenoid coil aiming for submillimeter resolution of the human pituitary gland. METHODS: Sphenoid sinus measurements determined coil design constraints for use in > 95% of adult patients. Temperature safety parameters were tested. The 2-cm-diameter coil prototype was positioned in the sphenoid sinus of cadaveric human heads utilizing the transnasal endoscopic approach that is used clinically. Signal-to-noise ratio (SNR) was estimated for the transnasal coil prototype compared with a standard clinical head coil. One cadaveric pituitary gland was explanted and histologically examined for correlation to the imaging findings. RESULTS: With the coil positioned directly atop the sella turcica at a 0° angle of the B0 static field, the craniocaudal distance (21.2 ± 0.8 mm) was the limiting constraint. Phantom experiments showed no detectable change in temperature at two sites over 15 minutes. The flexible coil was placed transnasally in cadaveric specimens using an endoscopic approach. The image quality was subjectively superior at higher spatial resolutions relative to that with the commercial 20-channel head coil. An average 17-fold increase in the SNR was achieved within the pituitary gland. Subtle findings visualized only with the transnasal coil had potential pathological correlation with immunohistochemical findings. CONCLUSIONS: A transnasal radiofrequency coil feasibly provides a 17-fold boost in the SNR at 3 T. The ability to safely improve the quality of pituitary imaging may be helpful in the identification and subsequent resection of small functional pituitary lesions.

High-Resolution 3D MRI With Deep Generative Networks via Novel Slice-Profile Transformation Super-Resolution.

High-resolution magnetic resonance imaging (MRI) sequences, such as 3D turbo or fast spin-echo (TSE/FSE) imaging, are clinically desirable but suffer from long scanning time-related blurring when reformatted into preferred orientations. Instead, multi-slice two-dimensional (2D) TSE imaging is commonly used because of its high in-plane resolution but is limited clinically by poor through-plane resolution due to elongated voxels and the inability to generate multi-planar reformations due to staircase artifacts. Therefore, multiple 2D TSE scans are acquired in various orthogonal imaging planes, increasing the overall MRI scan time. In this study, we propose a novel slice-profile transformation super-resolution (SPTSR) framework with deep generative learning for through-plane super-resolution (SR) of multi-slice 2D TSE imaging. The deep generative networks were trained by synthesized low-resolution training input via slice-profile downsampling (SP-DS), and the trained networks inferred on the slice profile convolved (SP-conv) testing input for 5.5x through-plane SR. The network output was further slice-profile deconvolved (SP-deconv) to achieve an isotropic super-resolution. Compared to SMORE SR method and the networks trained by conventional downsampling, our SPTSR framework demonstrated the best overall image quality from 50 testing cases, evaluated by two abdominal radiologists. The quantitative analysis cross-validated the expert reader study results. 3D simulation experiments confirmed the quantitative improvement of the proposed SPTSR and the effectiveness of the SP-deconv step, compared to 3D ground-truths. Ablation studies were conducted on the individual contributions of SP-DS and SP-conv, networks structure, training dataset size, and different slice profiles.

Transcriptomic analysis reveals immune infiltration status and potential biomarkers of canine colorectal cancer.

Colorectal cancer (CRC) in dogs has been shown to have similar molecular characteristics to human colorectal cancer. Although researchers have explored the pathogenesis and immune status of human CRC, the canine CRC has been far less studied. As a result, we analyzed canine colorectal tumors and normal canine intestinal samples by Gene Set Enrichment Analysis (GSEA) and found significant enrichment of immune-related pathways, including the TNF-α signaling pathway and IL6-STAT3 signaling pathway. In addition, the differential infiltration of naive B cells and regulatory T cells suggested that canine CRC was in a state of immunosuppression. Weighted gene co-expression network analysis (WGCNA) revealed the gene modules that contribute to differences in regulatory T cell inetfiltration, Further cross-validation of canine and human CRC differential genes obtained three core genes that are both species-conserved and differentially expressed, CD44, NAT10, and ETV4, of which NAT10 and ETV4 have been little studied in the immune status of colorectal cancer. Our findings may have implications for the pathogenesis and progression of CRC in dogs and could be a new potential therapeutic target for CMT and provide a bioinformatics foundation for later clinical experiment validation.

Tetramethylpyrazine-Rhein Derivative inhibits the migration of canine inflammatory mammary carcinoma cells by mitochondrial damage-mediated apoptosis and cadherins downregulation.

BACKGROUND: Canine inflammatory mammary carcinoma (CIMC) has a high incidence of metastasis, high lethality, and poor prognosis, which needs novel adjuvant agents. Tetramethylpyrazine-Rhein Derivative (TRD) has been shown to have antitumor activity, which is a potential research direction for CIMC. PURPOSE: This study evaluated the efficacy of TRD on CIMC in vitro and in vivo, and provided possibilities for the application of active compounds in traditional Chinese medicine. METHODS: In vitro, TRD cytotoxicity was measured with CCK-8. Flow cytometry and transmission electron microscope were used to detect the cell cycle, cell death, and changes in mitochondria. Wound-healing assay, cell invasion assay, and scanning electron microscope were used to evaluate the suppression of cell migration and invasion. Expression changes were detected by RT-qPCR and western blot assay. In vivo, the lung metastasis models were randomly divided into control, low-dose TRD, high-dose TRD, and positive groups. Each group was administered orally once a day for 18 days and took in vivo imaging photos. RESULTS: The IC50 of TRD in CHMp and MDCK were 42.59 and 79.37 µM, respectively. TRD mediated cell apoptosis by mitochondrial damage and caused S and G2/M phase arrest by downregulating cyclin B1. Moreover, TRD reduced filopodia and inhibited cell migration by downregulating cadherins. In CIMC lung metastasis models, TRD could effectively inhibit tumor growth (P < 0.001) in the lungs without significant toxicity. CONCLUSION: TRD showed potential activity to inhibit CIMC lung metastasis with multi-target and low toxicity.

Construction of a three-dimensional urothelium on-chip with barrier function based on urinary flow microenvironment.

The urothelium covers the inner surface of the urinary tract, forming a urinary tract barrier. Impairment of the integrity and dysfunction of the urinary tract barrier is associated with the occurrence and development of various diseases. The development of a three-dimensional model of the urothelium is critical for pathophysiological studies of this site, especially under physiological fluid shear stress stimulated by the urinary flow. In this study, a urothelium on-chip is fabricated with micromilling and replica molding techniques, which contains a microfluidic chip for cell culture and a pump-based fluid perfusion system. The mechanical properties of the human urinary tract are simulated by adjusting the concentration and degree of amino substitution of the gelatin methacrylate hydrogel. The matrix stiffness is similar to the natural urinary tract. Pulsatile flow and periodic flow are provided to simulate the fluid environment of the upper and lower urinary tracts, respectively. The results show that the physiological fluid shear stress could promote the differentiation and maturation of urothelial cells. The model could simulate the three-dimensional structure of urothelium and urinary flow microenvironment, showing morphological structure close to the natural urothelium, specific differentiation and maturation markers (uroplakin 2, cytokeratin 20), and urothelial barrier function.

Rapid and Sensitive Detection of Fungicide-Resistant Crop Fungal Pathogens Using an Isothermal Amplification Refractory Mutation System.

Fungicide abuse leads to the emergence of fungicide-resistant fungal pathogens, thus posing a threat to agriculture and food safety. Here, we developed an isothermal amplification refractory mutation system (termed iARMS) allowing us to resolve genetic mutations, enabling rapid, sensitive, and potentially field-applicable detection of fungicide-resistant crop fungal pathogens. iARMS yielded a limit of detection of 25 aM via a cascade signal amplification strategy of recombinase polymerase amplification (RPA) and Cas12a-mediated collateral cleavage at 37 °C within 40 min. Specificity for fungicide-resistant Puccinia striiformis (P. striiformis) detection was guaranteed by RPA primers and the flexible sequence of gRNA. The iARMS assay allowed us to detect as low as 0.1% cyp51-mutated P. striiformis that showed resistance to the demethylase inhibitor (DMI), which was 50 times more sensitive than the sequencing techniques. Thus, it is promising for the discovery of rare fungicide-resistant isolates. We applied iARMS to investigate the emergence of fungicide-resistant P. striiformis in western China and found that its proportion was over 50% in Qinghai, Sichuan, and Xinjiang Province. iARMS can serve as a molecular diagnostic tool for crop diseases and facilitate precision plant disease management.

Application of microfluidic chips in the simulation of the urinary system microenvironment.

The urinary system, comprising the kidneys, ureters, bladder, and urethra, has a unique mechanical and fluid microenvironment, which is essential to the urinary system growth and development. Microfluidic models, based on micromachining and tissue engineering technology, can integrate pathophysiological characteristics, maintain cell-cell and cell-extracellular matrix interactions, and accurately simulate the vital characteristics of human tissue microenvironments. Additionally, these models facilitate improved visualization and integration and meet the requirements of the laminar flow environment of the urinary system. However, several challenges continue to impede the development of a tissue microenvironment with controllable conditions closely resemble physiological conditions. In this review, we describe the biochemical and physical microenvironment of the urinary system and explore the feasibility of microfluidic technology in simulating the urinary microenvironment and pathophysiological characteristics in vitro. Moreover, we summarize the current research progress on adapting microfluidic chips for constructing the urinary microenvironment. Finally, we discuss the current challenges and suggest directions for future development and application of microfluidic technology in constructing the urinary microenvironment in vitro.

Comparison of tumor-derived total RNA and cell lysate on antitumor immune activity.

Tumor-derived total RNA (TdRNA) and cell lysate (TCL), with almost all the relevant tumor antigens, represent attractive alternative sources of antigens in antitumor immunotherapy. However, the comparison of their capacity to elicit immune responses against breast cancer is still lacking. In this study, the antitumor immune effects of TdRNA and TCL were systematically compared. We isolated TdRNA and TCL from 4T1 mouse breast cancer cells, and found that both sources of antigens could stimulate the maturation of dendritic cells (DCs) at the cellular and in vivo levels, and induce robust cellular immune responses, as evidenced by the increased percentages of both CD4+ and CD8+ T cells in the inguinal lymph nodes and spleen. But TdRNA performed stronger immunoactivities than TCL on the increase of T cell population through DCs activation. Additionally, the synergistic antitumor efficacy of paclitaxel (PTX) with TdRNA and TCL respectively was further evaluated in the murine 4T1 tumor model. Compared with TCL, TdRNA could inhibit tumor growth more effectively with low systemic toxicity when combined with PTX, which was, at least in part, attributable to the improvement of systemic immune function and tumor immune infiltration. Overall, TdRNA outperforms TCL in antitumor immunity, and is expected to be a promising candidate for application as the source of tumor antigens.

Nootkatone Supplementation Ameliorates Carbon Tetrachloride-Induced Acute Liver Injury via the Inhibition of Oxidative Stress, NF-κB Pathways, and the Activation of Nrf2/HO-1 Pathway.

Acute liver injury is a type of liver diseases, and it has raised concerns worldwide due to the lack of effective therapies. The aim of this study is to investigate the protective effects of nootkatone (NOOT) on carbon tetrachloride (CCl4)-caused acute liver injury in mice. Mice were randomly divided into control, CCl4 model, NOOT, and NOOT (5, 10, and 20 mg/kg/day) plus CCl4 groups, respectively. Mice in the CCl4 plus NOOT groups were orally administrated with NOOT at 5, 10, and 20 mg/kg/days for seven days prior to 0.3% CCl4 injection at 10 mL/kg body weight, respectively. Our results showed that NOOT supplementation significantly ameliorated CCl4-induced increases of serum AST and ALT levels, hepatocyte necrosis, inflammatory response, oxidative stress, and caspases-9 and -3 activities in the livers of mice. Moreover, NOOT supplementation significantly upregulated the expression of Nrf2 and HO-1 mRNAs but downregulated the expression of NF-κB mRNAs and the levels of IL-1ß, IL-6, and TNF-α proteins in the liver tissues, compared to those in the CCl4 model group. In conclusion, for the first time, our results reveal that NOOT could offer protective effects against CCl4-caused oxidative stress and inflammatory response via the opposite regulation of Nrf2/HO-1 pathway and NF-κB pathway.

Polysaccharides of Plantago asiatica enhance antitumor activity via regulating macrophages to M1-like phenotype.

Monocyte-derived macrophages can be polarized into antitumor M1 phenotype, which inhibited the growth of tumors, and immune-suppressive M2 phenotype, which promoted the development and metastasis of tumors. Plantain polysaccharide (PLP), extracted from the Plantago asiatica, has shown its various biological activities. However, the ability of PLP involved in immune regulation was still obscure. Accordingly, we aimed to investigate whether PLP could polarize macrophages and further inhibit 4T1 tumor cells in vivo and in vitro. In this research, in vitro results showed that PLP displayed the potential in polarizing RAW264.7 macrophages into M1 phenotype and indirect inhibiting migratory effect on 4T1 cells. Furthermore, the phagocytosis and the release of reactive oxygen species (ROS) of macrophages were enhanced. In vivo anti-tumor results demonstrated that PLP could effectively inhibit the growth of 4T1 breast tumors by promoting accumulation of macrophages and T cells in the spleen and lymph node. In conclusion, these findings indicated that PLP inhibited the proliferation and progression of breast tumors by accumulating CD4+, CD8+ T cells and M1-like macrophages in lymph node and spleen, and therefore provided an experimental basis for PLP as a potential antitumor adjunctive therapy in preclinical and clinical trials.

RNADisease v4.0: an updated resource of RNA-associated diseases, providing RNA-disease analysis, enrichment and prediction.

Numerous studies have shown that RNA plays an important role in the occurrence and development of diseases, and RNA-disease associations are not limited to noncoding RNAs in mammals but also exist for protein-coding RNAs. Furthermore, RNA-associated diseases are found across species including plants and nonmammals. To better analyze diseases at the RNA level and facilitate researchers in exploring the pathogenic mechanism of diseases, we decided to update and change MNDR v3.0 to RNADisease v4.0, a repository for RNA-disease association (http://www.rnadisease.org/ or http://www.rna-society.org/mndr/). Compared to the previous version, new features include: (i) expanded data sources and categories of species, RNA types, and diseases; (ii) the addition of a comprehensive analysis of RNAs from thousands of high-throughput sequencing data of cancer samples and normal samples; (iii) the addition of an RNA-disease enrichment tool and (iv) the addition of four RNA-disease prediction tools. In summary, RNADisease v4.0 provides a comprehensive and concise data resource of RNA-disease associations which contains a total of 3 428 058 RNA-disease entries covering 18 RNA types, 117 species and 4090 diseases to meet the needs of biological research and lay the foundation for future therapeutic applications of diseases.