Detoxification of Mycotoxin Patulin by the Yeast Kluyveromyces marxianus YG-4 in Apple Juice.

Patulin (PAT) is a mycotoxin produced by Penicillium species, which often contaminates fruit and fruit-derived products, posing a threat to human health and food safety. This work aims to investigate the detoxification of PAT by Kluyveromyces marxianus YG-4 (K. marxianus YG-4) and its application in apple juice. The results revealed that the detoxification effect of K. marxianus YG-4 on PAT includes adsorption and degradation. The adsorption binding sites were polysaccharides, proteins, and some lipids on the cell wall of K. marxianus YG-4, and the adsorption groups were hydroxyl groups, amino acid side chains, carboxyl groups, and ester groups, which were combined through strong forces (ion interactions, electrostatic interactions, and hydrogen bonding) and not easily eluted. The degradation active substance was an intracellular enzyme, and the degradation product was desoxypatulinic acid (DPA) without cytotoxicity. K. marxianus YG-4 can also effectively adsorb and degrade PAT in apple juice. The contents of organic acids and polyphenols significantly increased after detoxification, significantly improving the quality of apple juice. The detoxification ability of K. marxianus YG-4 toward PAT would be a novel approach for the elimination of PAT contamination.

Solvent and monomer regulation synthesis of core-shelled magnetic ß-cyclodextrin microporous organic network for efficient extraction of estrogens in biological samples prior to HPLC analysis.

The abnormal estrogens levels in human body can cause many side effects and diseases, but the quantitative detection of the trace estrogens in complex biological samples still remains great challenge. Here we reported the fabrication of a novel core-shell structured magnetic cyclodextrin microporous organic network (Fe3O4@CD-MON) for rapid magnetic solid phase extraction (MSPE) of four estrogens in human serum and urine samples prior to HPLC-UV determination. The uniform spherical core-shell Fe3O4@CD-MONs was successfully regulated by altering the reactive monomers and solvents. The Fe3O4@CD-MONs owned high specific surface area, good hydrophobicity, large superparamagnetism, and abundant extraction sites for estrogens. Under optimal conditions, the proposed MSPE-HPLC-UV method provided wide linearity range (2.0-400 µg L-1), low limits of detection (0.5-1.0 µg L-1), large enrichment factors (183-198), less adsorbent consumption (3 mg), short extraction time (3 min), and good stability and reusability (at least 8 cycles). The established method had also been successfully applied to the enrichment and detection of four estrogens in serum and urine samples with a recovery of 88.4-105.1 % and a relative standard deviation of 1.0-5.9 %. This work confirmed the feasibility of solvent and monomer regulation synthesis of Fe3O4@CD-MON composites, and revealed the great prospects of magnetic CD-MONs for efficient enrichment of trace estrogens in complex biological samples.

Magnesium oxide nanoparticles reduce clubroot by regulating plant defense response and rhizosphere microbial community of tumorous stem mustard (Brassica juncea var. tumida).

Clubroot, caused by Plasmodiophora brassicae, is a major disease that significantly impairs the yield of cruciferous crops and causes significant economic losses across the globe. The prevention of clubroot, especially in tumorous stem mustard (without resistant varieties), are is limited and primarily relies on fungicides. Engineered nanoparticles have opened up new avenues for the management of plant diseases, but there is no report on their application in the prevention of clubroot. The results showed that the control efficacy of 500 mg/L MgO NPs against clubroot was 54.92%. However, when the concentration was increased to 1,500 and 2,500 mg/L, there was no significant change in the control effect. Compared with CK, the average fresh and dry weight of the aerial part of plants treated with MgO NPs increased by 392.83 and 240.81%, respectively. Compared with the F1000 treatment, increases were observed in the content of soil available phosphorus (+16.72%), potassium (+9.82%), exchangeable magnesium (+24.20%), and water-soluble magnesium (+20.64%) in the 1,500 mg/L MgO NPs treatment. The enzyme-linked immune sorbent assay (ELISA) results showed that the application of MgO NPs significantly increased soil peroxidase (POD, +52.69%), alkaline protease (AP, +41.21%), alkaline phosphatase (ALP, +79.26%), urease (+52.69%), and sucrase (+56.88%) activities; And also increased plant L-phenylalanine ammonla-lyase (PAL, +70.49%), polyphenol oxidase (PPO, +36.77%), POD (+38.30%), guaiacol peroxidase (POX, +55.46%) activities and salicylic acid (SA, +59.86%) content. However, soil and plant catalase (CAT, -27.22 and - 19.89%, respectively), and plant super oxidase dismutase (SOD, -36.33%) activities were significantly decreased after the application of MgO NPs. The metagenomic sequencing analysis showed that the MgO NPs treatments significantly improved the α-diversity of the rhizosphere soil microbial community. The relative abundance of beneficial bacteria genera in the rhizosphere soil, including Pseudomonas, Sphingopyxis, Acidovorax, Variovorax, and Bosea, was significantly increased. Soil metabolic functions, such as oxidative phosphorylation (ko00190), carbon fixation pathways in prokaryotes (ko00720), indole alkaloid biosynthesis (ko00901), and biosynthesis of various antibiotics (ko00998) were significantly enriched. These results suggested that MgO NPs might control clubroot by promoting the transformation and utilization of soil nutrients, stimulating plant defense responses, and enriching soil beneficial bacteria.

Health information-seeking experience in people with head and neck neoplasms undergoing treatment: a qualitative study.

PURPOSE: To describe the health information-seeking experience and its influencing factors of people with head and neck neoplasms undergoing treatment. METHODS: This was a descriptive phenomenology study. Participants were recruited by purposive sampling. The semistructured interviews and all observation results were recorded. The data were analysed using Colaizzi's method. RESULTS: Fourteen participants were selected. We identified four themes that illustrate factors that influence the health information-seeking behaviour of participants: patients' awareness of health information needs, patients' competence, doctor-patient communication, and online advertising interference. We also determined the value of different types of information and patients' information needs and sources. CONCLUSION: These findings can help professionals understand patients' behaviours and think about how to deliver practical information support in a network environment to guide patients in continuous information seeking while taking specific factors into account.

Predicting isocitrate dehydrogenase genotype, histological phenotype, and Ki-67 expression level in diffuse gliomas with an advanced contrast analysis of magnetic resonance imaging sequences.

Background: The present study aimed to establish a robust predictive model based on a machine learning (ML) algorithm providing preoperative noninvasive diagnosis and to further explore the contribution of each magnetic resonance imaging (MRI) sequence to the classification to help select images for future model development. Methods: This was a retrospective cross-sectional study, and consecutive patients with histologically confirmed diffuse gliomas in our hospital from November 2015 to October 2019 were recruited. The participants were grouped into a training and testing set based on a ratio of 8:2. Five MRI sequences were employed to develop the support vector machine (SVM) classification model. An advanced contrast analysis of single-sequence-based classifiers was performed, according to which different sequence combinations were tested, and the best one was selected to form an ultimate classifier. Patients whose MRIs were acquired with other types of scanners formed an additional, independent validation set. Results: A total of 150 patients with gliomas were used in the present study. Contrast analysis revealed that the contribution of the apparent diffusion coefficient (ADC) was the most significant [accuracies were as follows: histological phenotype, 0.640; isocitrate dehydrogenase (IDH) status, 0.656; and Ki-67 expression, 0.699] and that of T1 weighted imaging was limited (accuracies were as follows: histological phenotype, 0.521; IDH status, 0.492; and Ki-67 expression, 0.556). The ultimate classifiers for IDH status, histological phenotype, and Ki-67 expression achieved promising performances with area under the curve (AUC) values of 0.88, 0.93, and 0.93, respectively. The classifiers for the histological phenotype, IDH status, and Ki-67 expression correctly predicted 3 of 5 subjects, 6 of 7 subjects, and 9 of 13 subjects in the additional validation set, respectively. Conclusions: The present study showed satisfactory performance in predicting the IDH genotype, histological phenotype, and Ki-67 expression level. The contrast analysis revealed the contribution of different MRI sequences and suggested that the combination of all the acquired sequences was not the optimal strategy to build the radiogenomics-based classifier.

Pelvic floor dysfunction and its influencing factors during radiotherapy in cervical cancer survivors: A cross-sectional study.

PURPOSE: Radiotherapy can negatively affect the pelvic floor function of patients with cervical cancer; however, the impact of different radiotherapy times and other related factors on pelvic floor function in cervical cancer survivors during radiotherapy remains unclear. We aimed to investigate the status of pelvic floor dysfunction (PFD) in cervical cancer survivors during radiotherapy and to analyze the factors influencing PFD. METHODS: In this cross-sectional study, a convenience sampling method was used to recruit cervical cancer survivors undergoing radiotherapy from January 2022 to July 2022 at a tertiary first-class hospital located in northeastern China. The Pelvic Floor Distress Inventory-Short Form 20 was used for participants' self-report of their PFD during radiotherapy. RESULTS: Data from 120 cervical cancer survivors were included in this study. The results showed that the mean PFDI-20 total score was 32.69 ± 7.76. Multiple stepwise linear regression analysis showed that 56.9% of the variance in PFD was explained by age (ß = 0.25, p < 0.001), body mass index (ß = 0.32, p < 0.001), recurrence (ß = 0.29, p < 0.001), number of radiotherapy sessions (ß = 0.39, p < 0.001), and number of deliveries (ß = 0.35, p < 0.001). CONCLUSION: It is important to pay more attention to the PFD status of cervical cancer survivors receiving radiotherapy. Future therapeutic approaches should involve early identification of relevant risk factors early to provide patients with personalized care at different stages of radiotherapy for reducing their discomfort and improving their health-related quality of life.

Psychosocial adjustment and its influencing factors among head and neck cancer survivors after radiotherapy: A cross-sectional study.

PURPOSE: Psychosocial adjustment is an important issue in patients' long-term survival. Understanding psychosocial adjustment and its influencing factors in head and neck cancer survivors after radiotherapy is essential to help them return to society and lead a normal life. The purpose of this study was to describe the level of psychosocial adjustment and explore its influencing factors in head and neck cancer patients. METHODS: Between May 2019 and May 2022, 253 head and neck cancer survivors at a tertiary hospital in northeast China were enrolled in a cross-sectional study. The research instruments comprised the Demographic and Clinical Characteristics Questionnaire, the Self-report Psychosocial Adjustment to Illness Scale (PAIS-SR), the General Self-efficacy Scale (GSES), the Social Support Rating Scale (SSRS) and the M.D. Anderson Symptom Survey-head and neck Questionnaire (MDASI-H&N). RESULTS: The mean PAIS-SR score was 42.31 ± 16.70 (moderate). The multiple regression model revealed that 73.2% of the variance in psychosocial adjustment was explained by marital status (ß = -0.114, P = 0.005), return to work or not (ß = -0.275, P < 0.01), self-efficacy (ß = -0.327, P < 0.01), subjective support (ß = -0.106, P = 0.043), utilization of support (ß = -0.172, P < 0.01), and trouble with symptoms in daily life (ß = 0.138, P = 0.021). CONCLUSION: The psychosocial adjustment of head and neck cancer survivors after radiotherapy is an issue that needs to be addressed, and medical staff should develop effective, individualized interventions to improve their psychosocial adjustment by increasing their social support, improving their self-efficacy and strengthening symptom management according to their actual situation.

Synthesis of crown ether-based microporous organic networks: A new type of efficient adsorbents for chlorophenols.

Microporous organic networks (MONs) are a booming class of functional materials in elimination of environmental pollutants. However, the limit varieties of MONs still restrict their broad applications. Here we report the synthesis of a novel type of crown ether (CE)-based MONs via the coupling between brominated 18-crown-6 ether and different aromatic alkynyls. The constructed CE-based MONs integrates the good conjugation property of MONs and the inherent host-guest binding sites of CE, allowing the ultrafast and efficient adsorption and removal of a typical environmental priority pollutant 2,4,6-trichlorophenol (2,4,6-TCP). The hydrophobic CE-based MONs can also address the recovery challenge of unstable discrete CE in most organic and inorganic solvents. All CE-based MONs displayed fast adsorption kinetics (< 3 min) and large adsorption capacities (229.1-341.7 mg g-1) for 2,4,6-TCP. The CE-based MONs also gave stable adsorption capacities for 2,4,6-TCP in pH range of 4.0-6.0, NaCl concentration of 0-40 mg L-1, HA concentration of 0-30 mg L-1, or H2O2 ratio of < 5 %. Density functional theory calculation, Fourier transform infrared and X-ray photoelectron spectra evaluation revealed adsorption process involved hydrophobic, π-π and hydrogen bonding interactions. The CE-based MONs also showed favorable reusability and good adsorption for other toxic chlorophenols. This work highlights the potential of CE-based MONs in contaminants elimination.

Effects of Baduanjin exercise in nasopharyngeal carcinoma patients after chemoradiotherapy: a randomized controlled trial.

OBJECTIVE: To evaluate the effects of traditional Chinese Baduanjin Qigong exercises on the physical and psychological recovery of patients with nasopharyngeal carcinoma after chemoradiotherapy. METHODS: Eighty-eight nasopharyngeal carcinoma patients who had completed chemoradiotherapy were randomly divided into the Baduanjin intervention group (n = 44) and the control group (n = 44). Patients in the intervention group practised Baduanjin exercise for 12 weeks, with the frequency of 40 min a day and 5 days a week after discharge from the hospital. Participants in the control group received usual care. Outcome indicators included quality of life (QOL), complications, cancer-related fatigue (CRF), sleep quality, anxiety, and depression. The intention-to-treat and per-protocol populations were compared using univariate analysis of variance. Partial eta squared was used as a measure of the effect size. RESULTS: A total of 75 patients completed the study. In the intention-to-treat analysis, after 12 weeks of exercise intervention, there were significant increases in the global FACT-H&N (95% CI = 2.09 to 11.47, ηp2 = 0.088), social/family well-being (95% CI = 0.13 to 2.26, ηp2 = 0.055), emotional well-being (95% CI = 0.34 to 2.44, ηp2 = 0.074), and head and neck cancer subscale scores (95% CI = 0.17 to 3.86, ηp2 = 0.052) in the Baduanjin group compared with the control group at the 12th week. In the per-protocol analysis, there were significant increases in the global FACT-H&N (95% CI = 4.11 to 11.75, ηp2 = 0.190), physical well-being (95% CI: 0.50 to 3.04, ηp2 = 0.096), social/family well-being (95% CI: 0.32 to 2.15, ηp2 = 0.090), emotional well-being (95% CI: 0.60 to 2.53, ηp2 = 0.125), functional well-being (95% CI: 0.25 to 2.49, ηp2 = 0.075), and head and neck cancer subscale (95% CI: 1.08 to 4.08, ηp2 = 0.139) scores in the Baduanjin group compared with the control group at the 12th week. CONCLUSION: The findings in this study indicate that Baduanjin exercise is an effective and appropriate intervention for improving quality of life and is worthy of recommendation and implementation by oncology nurses in the rehabilitation process of patients with nasopharyngeal carcinoma.

APETALA2/ethylene responsive factor in fruit ripening: Roles, interactions and expression regulation.

Insects and animals are attracted to, and feed on ripe fruit, thereby promoting seed dispersal. As a vital vitamin and nutrient source, fruit make up an indispensable and enjoyable component of the human diet. Fruit ripening involves a series of physiological and biochemical changes in, among others, pigmentation, chlorophyll (Chl) degradation, texture, sugar accumulation, and flavor. Growing evidence indicates that the coordinated and ordered trait changes during fruit ripening depend on a complex regulatory network consisting of transcription factors, co-regulators, hormonal signals, and epigenetic modifications. As one of the predominant transcription factor families in plants and a downstream component of ethylene signaling, more and more studies are showing that APETALA2/ethylene responsive factor (AP2/ERF) family transcription factors act as critical regulators in fruit ripening. In this review, we focus on the regulatory mechanisms of AP2/ERFs in fruit ripening, and in particular the recent results on their target genes and co-regulators. We summarize and discuss the role of AP2/ERFs in the formation of key fruit-ripening attributes, the enactment of their regulatory mechanisms by interaction with other proteins, their role in the orchestration of phytohormone-signaling networks, and the epigenetic modifications associated with their gene expression. Our aim is to provide a multidimensional perspective on the regulatory mechanisms of AP2/ERFs in fruit ripening, and a reference for understanding and furthering research on the roles of AP2/ERF in fruit ripening.

Copper phyllosilicate-derived ultrafine copper nanoparticles with plenty of Cu0and Cu+ for the enhanced catalytic performance of ethylene carbonate hydrogenation to methanol.

The hydrogenation of CO2-derived carbonates to methanol is an alternative route for the indirect utilization of abundant C1 sources. Various Cu/SiO2catalysts with different copper loading content prepared by using an ammonia evaporation hydrothermal method are implemented to evaluate the catalytic performance of ethylene carbonate (EC) hydrogenation to methanol and ethylene glycol (EG). The Cu loading content was identified to significantly affect the Cu nanoparticles (NPs) size and metal-support interaction. Highly dispersed Cu NPs restricted and embedded in copper phyllosilicate presented a smaller average particle size than the impregnated Cu/SiO2-IM catalyst. ThexCu/SiO2catalyst with ultrafine Cu NPs showed abundant Cu-O-Si interfaces, acidic sites, and coherent Cu0and Cu+species. The 5Cu/SiO2catalyst achieved methanol yield of 76% and EG yield of 98% at EC conversion of 99%, and no obvious deactivation was observed after long-term operation. The superior catalytic performance of the 5Cu/SiO2catalyst is attributed to the synergetic effect between the appropriate Cu0surface area which provides sufficient active hydrogen, and the atomic ratio of Cu+for the polarization and activation of carbon-oxygen bonds.

Genome-Wide Analysis and Expression Profiles of Ethylene Signal Genes and Apetala2/Ethylene-Responsive Factors in Peanut (Arachis hypogaea L.).

Peanut is an important oil and economic crop widely cultivated in the world. It has special characteristics such as blooming on the ground but bearing fruits underground. During the peg penetrating into the ground, it is subjected to mechanical stress from the soil at the same time. It has been proved that mechanical stress affects plant growth and development by regulating the ethylene signaling-related genes. In this study, we identified some genes related to ethylene signal of peanut, including 10 ethylene sensors, two constitutive triple responses (CTRs), four ethylene insensitive 2 (EIN2s), four ethylene insensitive 3 (EIN3s), six EIN3-binding F-box proteins (EBFs), and 188 Apetala2/ethylene-responsive factors (AP2/ERFs). One hundred and eighty-eight AP2/ERFs were further divided into four subfamilies, 123 ERFs, 56 AP2s, 6 Related to ABI3/VP1 (RAVs), and three Soloists, of them one hundred and seventy AP2/ERF gene pairs were clustered into segmental duplication events in genome of Arachis hypogaea. A total of 134, 138, 97, and 150 AhAP2/ERF genes formed 210, 195, 166, and 525 orthologous gene pairs with Arachis duranensis, Arachis ipaensis, Arabidopsis thaliana, and Glycine max, respectively. Our transcriptome results showed that two EIN3s (Arahy.J729H0 and Arahy.S7XF8N) and one EBFs (Arahy.G4JMEM) were highly expressed when mechanical stress increased. Among the 188 AhAP2/ERF genes, there were 31 genes with the fragments per kilobase of exon model per million mapped fragments (FPKM) ≥ 100 at least one of the 15 samples of Tifrunner. Among them, three AhAP2/ERFs (Arahy.15RATX, Arahy.FAI7YU, and Arahy.452FBF) were specifically expressed in seeds and five AhAP2/ERFs (Arahy.HGAZ7D, Arahy.ZW7540, Arahy.4XS3FZ, Arahy.QGFJ76, and Arahy.AS0C7C) were highly expressed in the tissues, which responded mechanical stress, suggesting that they might sense mechanical stress. Mechanical stress simulation experiment showed that three AhAP2/ERFs (Arahy.QGFJ76, Arahy.AS0C7C, and Arahy.HGAZ7D) were sensitive to mechanical stress changes and they all had the conservative repressor motif (DLNXXP) in the C-terminus, indicated that they might transmit mechanical stress signals through transcriptional inhibition. This study reveals the regulatory landscape of ethylene signal-related genes in peanut, providing valuable information for the mining of target genes for further study.

6:2 Chlorinated polyfluoroalkyl ether sulfonate as perfluorooctanesulfonate alternative in the electroplating industry and the receiving environment.

Electroplating industry is an important application field of per- and polyfluoroalkyl substances (PFASs) as the chromium mist suppressants. 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFAES) and perfluorooctanesulfonate (PFOS) have been the two widely used mist suppressants, and after the ban of PFOS, 6:2 Cl-PFAES will become the dominant suppressant. The behavior and mechanisms of 6:2 Cl-PFAES in the electroplating industry and the receiving environment were studied and compared with PFOS. 6:2 Cl-PFAES behaved similarly with PFOS due to their similar chemical structure. However, some difference exists for the relatively stronger hydrophobicity of 6:2 Cl-PFAES. Up to 35.7 mg/L of PFOS and 13.4 mg/L of 6:2 Cl-PFAES were found in the industrial wastewater influents, and were effectively reduced to 0.3-0.8 mg/L by the interaction with chromium hydroxide through hydrophobic interaction and ligand exchange. The stronger hydrophobicity of 6:2 Cl-PFAES than PFOS resulted in its accumulation in the surface of foams and comparable or less removal during the industrial and municipal wastewater treatment. 6:2 Cl-PFAES exhibited higher bioaccumulation potential than PFOS in the surface water. 6:2 Cl-PFAES emitted by both mists and water may pose health risks to humans. More attentions towards 6:2 Cl-PFAES are needed after the replacement of PFOS by it in the electroplating industry as a global contaminant of emerging concerns.

Knockdown of circ_0003928 ameliorates high glucose-induced dysfunction of human tubular epithelial cells through the miR-506-3p/HDAC4 pathway in diabetic nephropathy.

BACKGROUND: Previous data have indicated the importance of circular RNA (circRNA) in the pathogenesis of diabetic nephropathy (DN). The study is designed to investigate the effects of circ_0003928 on oxidative stress and apoptosis of high glucose (HG)-treated human tubular epithelial cells (HK-2) and the underlying mechanism. METHODS: The DN cell model was established by inducing HK-2 cells using 30 mmol/L D-glucose. RNA expression of circ_0003928, miR-506-3p and histone deacetylase 4 (HDAC4) was detected by quantitative real-time polymerase chain reaction. Cell viability and proliferation were investigated by cell counting kit-8 and 5-Ethynyl-29-deoxyuridine (EdU) assays, respectively. Oxidative stress was evaluated by commercial kits. Caspase 3 activity and cell apoptotic rate were assessed by a caspase 3 activity assay and flow cytometry analysis, respectively. Protein expression was detected by Western blotting analysis. The interactions among circ_0003928, miR-506-3p and HDAC4 were identified by dual-luciferase reporter and RNA pull-down assays. RESULTS: Circ_0003928 and HDAC4 expression were significantly upregulated, while miR-506-3p was downregulated in the serum of DN patients and HG-induced HK-2 cells. HG treatment inhibited HK-2 cell proliferation, but induced oxidative stress and cell apoptosis; however, these effects were reversed after circ_0003928 depletion. Circ_0003928 acted as a miR-506-3p sponge, and HDAC4 was identified as a target gene of miR-506-3p. Moreover, the circ_0003928/miR-506-3p/HDAC4 axis regulated HG-induced HK-2 cell dysfunction. CONCLUSION: Circ_0003928 acted as a sponge for miR-506-3p to regulate HG-induced oxidative stress and apoptosis of HK-2 cells through HDAC4, which suggested that circ_0003928 might be helpful in the therapy of DN.

A Novel Role of Nogo Proteins: Regulating Macrophages in Inflammatory Disease.

Nogo proteins, also known as Reticulon-4, have been identified as myelin-derived inhibitors of neurite outgrowth in the central nervous system (CNS). There are three Nogo variants, Nogo-A, Nogo-B and Nogo-C. Recent studies have shown that Nogo-A/B is abundant in macrophages and may have a wider effect on inflammation. In this review, we focus mainly on the possible roles of Nogo-A/B on polarization and recruitment of macrophages and their involvement in a variety of inflammatory diseases. We then discuss the Nogo receptor1 (NgR1), a common receptor for Nogo proteins that is also abundant in microglia/macrophage in the CNS. Interaction of Nogo and NgR1 in microglia/macrophage may affect the adhesion and polarization of macrophages that are involved in multiple neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis. Overall, this review provides insights into the roles of Nogo proteins in regulating macrophage functions and suggests that, potentially, Nogo proteins maybe a new target in the treatment of inflammatory diseases.

Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. AIM OF THE STUDY: To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. MATERIALS AND METHODS: Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. RESULTS: Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1ß, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. CONCLUSION: These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases.

lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p.

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was reported as an oncogene in many tumors including retinoblastoma (RB). This research mainly focused on the functions and mechanism of MALAT1 in RB. MALAT1 was upregulated in RB tissues and cells, and it served as a competing endogenous RNA (ceRNA) and inhibited miRNA-655-3p (miR-655-3p) expression, which eventually regulated the expression of miR-655-3p downstream target ATPase Family AAA Domain Containing 2 (ATAD2). The level of ATAD2 significantly increased, while that of miR-655-3p remarkably decreased in RB tissues and cells. MALAT1 depletion inhibited cell proliferation, metastasis, and epithelial-mesenchymal transition (EMT), but promoted apoptosis in vitro and blocked xenograft tumor growth in vivo. MALAT1 exerted its oncogenic functions in RB by regulating miR-655-3p/ATAD2 axis.

Papain-Like Cysteine Protease Gene Family in Fig (Ficus carica L.): Genome-Wide Analysis and Expression Patterns.

The papain-like cysteine proteases (PLCPs) are the most abundant family of cysteine proteases in plants, with essential roles in biotic/abiotic stress responses, growth and senescence. Papain, bromelain and ficin are widely used in food, medicine and other industries. In this study, 31 PLCP genes (FcPCLPs) were identified in the fig (Ficus carica L.) genome by HMM search and manual screening, and assigned to one of nine subfamilies based on gene structure and conserved motifs. SAG12 and RD21 were the largest subfamilies with 10 and 7 members, respectively. The FcPCLPs ranged from 1,128 to 5,075 bp in length, containing 1-10 introns, and the coding sequence ranged from 624 to 1,518 bp, encoding 207-505 amino acids. Subcellular localization analysis indicated that 24, 2, and 5 PLCP proteins were targeted to the lysosome/vacuole, cytoplasm and extracellular matrix, respectively. Promoter (2,000 bp upstream) analysis of FcPLCPs revealed a high number of plant hormone and low temperature response elements. RNA-seq revealed differential expression of 17 FcPLCPs in the inflorescence and receptacle, and RD21 subfamily members were the major PLCPs expressed in the fruit; 16 and 5 FcPLCPs responded significantly to ethylene and light, respectively. Proteome analyses revealed 18 and 5 PLCPs in the fruit cell soluble proteome and fruit latex, respectively. Ficins were the major PLCP in fig fruit, with decreased abundance in inflorescences, but increased abundance in receptacles of commercial-ripe fruit. FcRD21B/C and FcALP1 were aligned as the genes encoding the main ficin isoforms. Our study provides valuable multi-omics information on the FcPLCP family and lays the foundation for further functional studies.

Predictive Role of the Apparent Diffusion Coefficient and MRI Morphologic Features on IDH Status in Patients With Diffuse Glioma: A Retrospective Cross-Sectional Study.

PURPOSE: To evaluate isocitrate dehydrogenase (IDH) status in clinically diagnosed grade II~IV glioma patients using the 2016 World Health Organization (WHO) classification based on MRI parameters. MATERIALS AND METHODS: One hundred and seventy-six patients with confirmed WHO grade II~IV glioma were retrospectively investigated as the study set, including lower-grade glioma (WHO grade II, n = 64; WHO grade III, n = 38) and glioblastoma (WHO grade IV, n = 74). The minimum apparent diffusion coefficient (ADCmin) in the tumor and the contralateral normal-appearing white matter (ADCn) and the rADC (ADCmin to ADCn ratio) were defined and calculated. Intraclass correlation coefficient (ICC) analysis was carried out to evaluate interobserver and intraobserver agreement for the ADC measurements. Interobserver agreement for the morphologic categories was evaluated by Cohen's kappa analysis. The nonparametric Kruskal-Wallis test was used to determine whether the ADC measurements and glioma subtypes were related. By univariable analysis, if the differences in a variable were significant (P<0.05) or an image feature had high consistency (ICC >0.8; κ >0.6), then it was chosen as a predictor variable. The performance of the area under the receiver operating characteristic curve (AUC) was evaluated using several machine learning models, including logistic regression, support vector machine, Naive Bayes and Ensemble. Five evaluation indicators were adopted to compare the models. The optimal model was developed as the final model to predict IDH status in 40 patients with glioma as the subsequent test set. DeLong analysis was used to compare significant differences in the AUCs. RESULTS: In the study set, six measured variables (rADC, age, enhancement, calcification, hemorrhage, and cystic change) were selected for the machine learning model. Logistic regression had better performance than other models. Two predictive models, model 1 (including all predictor variables) and model 2 (excluding calcification), correctly classified IDH status with an AUC of 0.897 and 0.890, respectively. The test set performed equally well in prediction, indicating the effectiveness of the trained classifier. The subgroup analysis revealed that the model predicted IDH status of LGG and GBM with accuracy of 84.3% (AUC = 0.873) and 85.1% (AUC = 0.862) in the study set, and with the accuracy of 70.0% (AUC = 0.762) and 70.0% (AUC = 0.833) in the test set, respectively. CONCLUSION: Through the use of machine-learning algorithms, the accurate prediction of IDH-mutant versus IDH-wildtype was achieved for adult diffuse gliomas via noninvasive MR imaging characteristics, including ADC values and tumor morphologic features, which are considered widely available in most clinical workstations.