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Abstract Dental pulp regeneration is significantly aided by human dental pulp stem cells (hDPSCs). An increasing number of studies have demonstrated that circular RNAs (circRNAs) are crucial in the multidirectional differentiation of many mesenchymal stem cells, but their specific functions and mechanisms remain unknown. This work aimed at elucidating the molecular mechanism by which hsa_circ_0001599 works in hDPSCs during odontogenic differentiation. The expression of hsa_circ_0001599 in hDPSCs and dental pulp tissue was determined by using quantitative real-time PCR (qRT‒PCR). The role of hsa_circ_0001599 in the odontogenic differentiation of hDPSCs and its mechanism were studied using a variety of in vivo and in vitro assessments. The odontogenic differentiation of hDPSCs was facilitated by the overexpression of hsa_circ_0001599, which activated the PI3K/AKT signalling pathway in vitro. In vivo, hsa_circ_0001599 can promote the formation of new dentin-like structures. Mechanistically, hsa_circ_0001599 enhanced ITGA2 expression by sponging miR-889-3p. Furthermore, hsa_circ_0001599 interacts with the methylation reader hnRNPA2B1, promoting hnRNPA2B1 translocation from the nucleus to the cytoplasm and increasing ITGA2 mRNA stability. This research revealed the important role of hsa_circ_0001599 in odontogenic differentiation. Thus, hDPSCs engineered with hsa_circ_0001599 have the potential to be effective therapeutic targets for dental pulp repair and regeneration.

Abstract Effective antibacterial therapy while accelerating the repair of bone defects is crucial for the treatment of osteomyelitis. Inspired by the protective mechanism of Andrias davidianus, we constructed an antibacterial hydrogel scaffold with excellent rigidity and long-term slow-release activity. While retaining the toughness of the skin secretion of Andrias davidianus (SSAD), the rigidity of the hydrogel material is increased by incorporating hydroxyapatite to meet the demands of bone-defect-filling materials. It also exerted antibacterial effects via the slow-release of vancomycin from local osteomyelitis lesions. Notably, the hydrogel can also carry a high stable recombinant miR-214-3p inhibitor (MSA-anti214). By the delivery of nano vector polyvinylamine, the long-term slow-release of MSA-anti214 is achieved to promote bone repair, making this composite hydrogel a potential SSAD-based osteomyelitis alleviator (SOA). In vitro and vivo results verified that the SOA effectively eliminated Staphylococcus aureus and repaired bone defects, ultimately mitigating the progression of osteomyelitis. This composite hydrogel extends the economic application prospects of A. davidianus and has provided new insights for the treatment of osteomyelitis. The study also explored new insights for the bone filling materials of bone defection and other skeletal system diseases.

ABSTRACT Aim This study was to establish a scientific and sensitive index system of the biosafety incident response competence for clinical nursing staff to provide a reference for the evaluation of nurses' biosafety incident response competence. Design A modified recommendation for the conducting and reporting of Delphi studies was used to guide this study. Methods According to the literature review, preliminary biosafety incident response competence indicators for nursing staff were established, and an expert survey questionnaire was designed. The evaluation system for clinical nurses' biosafety incident response competence indicators was determined using the Delphi method. Results After two‐round Delphi survey, 28 nursing specialists from six provinces and cities around China, with expertise in three prevention research, epidemiology, military health service and biosafety incident rescue, established the index system of the biosafety incident response competence for nursing staff from April to May 2023. The final index system of the biosafety incident response competence was composed of four primary indicators, namely, biosafety incident preparedness, monitoring competence, protection ability and nursing disposal abilities; 10 secondary indicators and 49 tertiary indicators. The effective recovery rates of the two rounds of expert survey questionnaires were 93.33% and 100%, respectively. The authority coefficient, judgement coefficient and familiarity degree of Delphi experts were 0.877, 0.911 and 0.843, respectively. The Kendall's harmony coefficients of the two rounds of expert consultation were 0.301–0.384 and 0.401–0.424, respectively, with statistical significance (p

[This corrects the article DOI: 10.1371/journal.pone.0283137.].

Biomass-related airborne fine particulate matter (PM2.5) is an important risk factor for chronic obstructive pulmonary disease (COPD). Macrophage polarization has been reported to be involved in PM2.5-induced COPD, but the dynamic characteristics and underlying mechanism of this process remain unclear. Our study established a PM2.5-induced COPD mouse model and revealed that M2 macrophages predominantly presented after 4 and 6 months of PM2.5 exposure, during which a notable increase in MMP12 was observed. Single cell analysis of lung tissues from COPD patients and mice further revealed that M2 macrophages were the dominant macrophage subpopulation in COPD, with MMP12 being involved as a hub gene. In vitro experiments further demonstrated that PM2.5 induced M2 polarization and increased MMP12 expression. Moreover, we found that PM2.5 increased IL-4 expression, STAT6 phosphorylation and nuclear translocation. Nuclear pSTAT6 then bound to the MMP12 promoter region. Furthermore, the inhibition of STAT6 phosphorylation effectively abrogated the PM2.5-induced increase in MMP12. Using a coculture system, we observed a significantly reduced level of E-cadherin in alveolar epithelial cells cocultured with PM2.5-exposed macrophages, while the decrease in E-cadherin was reversed by the addition of an MMP12 inhibitor to the co-culture system. Taken together, these findings indicated that PM2.5 induced M2 macrophage polarization and MMP12 upregulation via the IL-4/STAT6 pathway, which resulted in alveolar epithelial barrier dysfunction and excessive extracellular matrix (ECM) degradation, and ultimately led to COPD progression. These findings may help to elucidate the role of macrophages in COPD, and suggest promising directions for potential therapeutic strategies.

Background: Esophageal cancer (ESCA) is a prevalent malignancy with a high incidence of morbidity and mortality, particularly in Asia. Telomeric Repeat-binding Factor 2 (TERF2) is a crucial component of the telomere-binding protein complex that maintains telomere stability. Aberrant TERF2 expression has been implicated in tumorigenesis, however, its specific role in ESCA remains largely unexplored. Methods: The expression levels of TERF2 were assessed in esophageal squamous cell carcinoma (ESCC) samples using RT-PCR, IHC, and Western blotting (WB). Serum tumor marker concentrations were determined via electrochemiluminescence immunoassay (ECLIA) and chemiluminescent microparticle immunoassay (CMIA). Bioinformatics analyses were employed to elucidate TERF2's function in EC. The impact of TERF2 on ESCC cell proliferation was evaluated through cell counting kit-8 (CCK8) assays and flow cytometry. Results: TERF2 protein and mRNA expression were elevated in ESCC tissues and correlated with age, sex, cancer stage, tumor grade, lymph node metastasis (LNM), and tumor histology. Univariate Cox regression analysis indicated TERF2 was an independent prognostic factor for overall survival (OS). TERF2 mRNA levels were associated with serum levels of carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and tissue polypeptide antigen (TPA) in patients with ESCC. Immune infiltration and chemokine profiles were linked to TERF2 expression in ESCA. TERF2 is involved in regulating ESCC cell proliferation may through the DDR/P53 signaling way. Conclusions: TERF2 is overexpressed in ESCA and contributes to ESCC cell proliferation may via DDR/TP53 signaling pathway. These results suggest that TERF2 may serve as a potential target for developing treatments and diagnostic biomarker for ESCA.

Abstract The DNA‐guided (gDNA) Argonaute from Thermus thermophilus (TtAgo) has little potential for nucleic acid detection and gene editing due to its poor dsDNA cleavage activity at relatively low temperature. Herein, the dsDNA cleavage activity of TtAgo is enhanced by using 2′‐fluorine (2′F)‐modified gDNA and developes a novel nucleic acid testing strategy. This study finds that the gDNA with 2′F‐nucleotides at the 3′‐end (2′F‐gDNA) can promote the assembly of the TtAgo‐guide‐target ternary complex significantly by increasing its intermolecular force to target DNA and TtAgo, thereby providing ≈40‐fold activity enhancement and decreasing minimum reaction temperature from 65 to 60 °C. Based on this outstanding advance, a novel nucleic acid testing strategy is proposed, termed FAST, which is performed by using the 2′F‐gDNA/TtAgo for target recognition and combining it with Bst DNA polymerase for nucleic acid amplification. By integrating G‐quadruplex and Thioflavin T, the FAST assay achieves one‐pot real‐time fluorescence analysis with ultra‐sensitivity, providing a limit of detection up to 5 copies (20 µL reaction mixture) for miR‐21 detection. In summary, an atom‐modification‐based strategy has been developed for enhancing the cleavage activity of TtAgo efficiently, thereby improving its practicability and establishing a TtAgo‐based nucleic acid testing technology with ultra‐sensitivity and high‐specificity.

Abstract With an estimated one million new cases reported annually, gastric cancer (GC) ranks as the fifth most diagnosed malignancy worldwide. The early detection of GC remains a major challenge, and the prognosis worsens either when patients develop resistance to chemotherapy or radiotherapy or when the cancer metastasizes. The precise pathogenesis underlying GC is not well understood, which further complicates its treatment. Circular RNAs (circRNAs), a recently discovered class of noncoding RNAs that originate from parental genes through “back-splicing”, have been shown to play a key role in various biological processes in both eukaryotes and prokaryotes. CircRNAs have been linked to cardiovascular diseases, diabetes, hypertension, Alzheimer's disease, and the occurrence and progression of tumors. Prior studies have established that circRNAs play a crucial role in GC, impacting tumorigenesis, diagnosis, progression, and therapy resistance. This review aims to summarize how circRNAs contribute to GC tumorigenesis and progression, examine their roles in the development of drug resistance, discuss their potential as biotechnological drugs, and summarize their response to therapeutic drugs and microorganism in GC.

Abstract Background The molecular mechanisms underlying the onset and progression of irreversible pulpitis have been studied for decades. Many studies have indicated a potential correlation between autophagy and this disease. Against the background of the competing endogenous RNA (ceRNA) theory, protein-coding RNA functions are linked with long noncoding RNAs (lncRNAs) and microRNAs (miRNAs). This mechanism has been widely studied in various fields but has rarely been reported in the context of irreversible pulpitis. The hub genes selected under this theory may represent the key to the interaction between autophagy and irreversible pulpitis. Results Filtering and differential expression analyses of the GSE92681 dataset, which contains data from 7 inflamed and 5 healthy pulp tissue samples, were conducted. The results were intersected with autophagy-related genes (ARGs), and 36 differentially expressed ARGs (DE-ARGs) were identified. Functional enrichment analysis and construction of the protein‒protein interaction (PPI) network of DE-ARGs were performed. Coexpression analysis was conducted between differentially expressed lncRNAs (DElncRNAs) and DE-ARGs, and 151 downregulated and 59 upregulated autophagy-related DElncRNAs (AR-DElncRNAs) were identified. StarBase and multiMiR were then used to predict related microRNAs of AR-DElncRNAs and DE-ARGs, respectively. We established ceRNA networks including 9 hub lncRNAs (HCP5 and AC112496.1 ↑; FENDRR, AC099850.1, ZSWIM8-AS1, DLX6-AS1, LAMTOR5-AS1, TMEM161B-AS1 and AC145207.5 ↓), which were validated by a qRT‒PCR analysis of pulp tissue from patients with irreversible pulpitis. Conclusion We constructed two networks consisting of 9 hub lncRNAs based on the comprehensive identification of autophagy-related ceRNAs. This study may provide novel insights into the interactive relationship between autophagy and irreversible pulpitis and identifies several lncRNAs that may serve as potential biological markers.

At present, artificial intelligence is in a period of rapid development, and deep learning has begun to be applied in various fields. Data, as a key part of the deep learning, its efficiency and stability, will directly affect the performance of the model, so it is valued by people. In order to make the dataset efficient, many active learning methods have been proposed, the dataset containing independent identically distribution (IID) samples is reduced with excellent performance; in order to make the dataset more stable, it should be solved that the model encounters out-of-distribution (OOD) samples to improve generalization performance. However, the current active learning method design and the method of adding OOD samples lack guidance, and people do not know what samples should be selected and which OOD samples will be added to better improve the generalization performance. In this paper, we propose a dataset containing a variety of elements called a dataset with Complete Sample Elements(CSE), the labels such as rotation angle and distance in addition to the common classification labels. These labels can help people analyze the distribution characteristics of each element of an efficient dataset, thereby inspiring new active learning methods; we also construct a corresponding OOD test set, which can not only detect the generalization performance of the model, but also helps explore metrics between OOD samples and existing dataset to guide the selected method of OOD samples, so that it can improve generalization efficiently. In this paper, we explore the distribution characteristics of efficient datasets in terms of angle element, and confirm that an efficient dataset tends to contain samples with different appearance. At the same time, experiments have proved the positive influence of the addition of OOD samples on the generalization performance of dataset.

Long non-coding RNAs (LncRNAs) play essential roles in multiple physiological processes including bone formation. Investigators have revealed that LncRNAs regulated bone formation through various signaling pathways and micro RNAs (miRNAs). However, several problems exist in current research studies on osteogenic LncRNAs, including sophisticated techniques, high cost for in vivo experiment, as well as low homology of LncRNAs between animal model and human, which hindered translational medicine research. Moreover, compared with gene editing, LncRNAs would only lead to inhibition of target genes rather than completely knocking them out. As the studies on osteogenic LncRNA gradually proceed, some of these problems have turned osteogenic LncRNA research studies into slump. This review described some new techniques and innovative ideas to address these problems. Although investigations on osteogenic LncRNAs still have obtacles to overcome, LncRNA will work as a promising therapeutic drug for osteoporosis in the near future.

Abstract Background Blueberry is one of the most important fruit crops worldwide. Anthocyanin is an important secondary metabolites that affects the appearance and nutritive quality of blueberries. However, few studies have focused on the molecular mechanism underlying anthocyanin accumulation induced by light intensity in blueberries. Results The metabolic analysis revealed that there were 134 significantly changed metabolites in the natural light compared to the control, and flavone, flavonol, and anthocyanins were the most significantly increased. Transcriptome analysis found 6 candidate genes for the anthocyanin synthesis pathway. Quantitative reverse transcription PCR (qRT-PCR) results confirmed changes in the expression levels of genes encoding metabolites involved in the flavonoid synthesis pathways. The flavonoid metabolic flux in the light intensity-treatment increased the accumulation of delphinidin-3-O-arabinoside compared to under the shading-treatment. Furthermore, we performed qRT-PCR analysis of anthocyanin biosynthesis genes and predicted that the gene of VcF3’5’H4 may be a candidate gene for anthocyanin accumulation and is highly expressed in light intensity-treated fruit. Through the co-expression analysis of transcription factors and anthocyanin synthesis pathway genes, we found that the VcbHLH004 gene may regulate VcF3’5’H4, and then we transformed VcbHLH004 heterologously into tomato to verify its function. Conclusion These results provide novel insights into light intensity regulation of blueberry anthocyanin accumulation and represent a valuable data set to guide future functional studies and blueberry breeding.

Abstract With the rise of artificial intelligence, deep learning is gradually applied to the field of agriculture and plant science. However, the excellent performance of deep learning needs to be established on massive numbers of samples. In the field of plant science and biology, it is not easy to obtain a large amount of labeled data. The emergence of few-shot learning solves this problem. It imitates the ability of humans’ rapid learning and can learn a new task with only a small number of labeled samples, which greatly reduces the time cost and financial resources. At present, the advanced few-shot learning methods are mainly divided into four categories based on: data augmentation, metric learning, external memory, and parameter optimization, solving the over-fitting problem from different viewpoints. This review comprehensively expounds on few-shot learning in smart agriculture, introduces the definition of few-shot learning, four kinds of learning methods, the publicly available datasets for few-shot learning, various applications in smart agriculture, and the challenges in smart agriculture in future development.

Abstract Background Particular matter 2.5 (PM2.5) is one of the most important air pollutant, and it is positively associated with the development of chronic obstructive pulmonary disease (COPD). However, the precise underlying mechanisms through which PM2.5 promotes the development of COPD remains largely unknown. Methods Mouse alveolar destruction were determined by histological analysis of lung tissues and lung function test. Alveolar type II cells (AT2) to alveolar type I cells (AT1) transition in PM2.5-induced COPD mouse model was confirmed via immunofluorescence staining and qPCR analysis. The differentially expressed genes in PM2.5-induced COPD mouse model were identified by RNA-sequencing of alveolar epithelial organoids and generated by bioinformatics analysis. Results In this study, we found that 6 months exposure of PM2.5 induced a significantly decreased pulmonary compliance and resulted in pulmonary emphysema in mice. We showed that PM2.5 exposure significantly reduced the AT2 to AT1 cell transition in vitro and in vivo. In addition, we found a reduced expression of the intermediate AT2-AT1 cell process marker claudin 4 (CLDN4) at day 4 of differentiation in mouse alveolar organoids treated with PM2.5, suggesting that PM2.5 exposure inhibited AT2 cells from entering the transdifferentiation process. RNA-sequencing of mouse alveolar organoids showed that several key signaling pathways that involved in the AT2 to AT1 cell transition were significantly altered including the Wnt signaling, MAPK signaling and signaling pathways regulating pluripotency of stem cells following PM2.5 exposure. Conclusions In summary, these data demonstrate a critical role of AT2 to AT1 cell transition in PM2.5-induced COPD mouse model and reveal the signaling pathways that potentially regulate AT2 to AT1 cell transition during this process. Our findings therefore advance the current knowledge of PM2.5-induced COPD and may lead to a novel therapeutic strategy to treat this disease.

BackgroundLow temperature is conducive to the survival of COVID-19. Some studies suggest that cold-chain environment may prolong the survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and increase the risk of transmission. However, the effect of cold-chain environmental factors and packaging materials on SARS-CoV-2 stability remains unclear.MethodsThis study aimed to reveal cold-chain environmental factors that preserve the stability of SARS-CoV-2 and further explore effective disinfection measures for SARS-CoV-2 in the cold-chain environment. The decay rate of SARS-CoV-2 pseudovirus in the cold-chain environment, on various types of packaging material surfaces, i.e., polyethylene plastic, stainless steel, Teflon and cardboard, and in frozen seawater was investigated. The influence of visible light (wavelength 450 nm-780 nm) and airflow on the stability of SARS-CoV-2 pseudovirus at -18°C was subsequently assessed.ResultsExperimental data show that SARS-CoV-2 pseudovirus decayed more rapidly on porous cardboard surfaces than on nonporous surfaces, including polyethylene (PE) plastic, stainless steel, and Teflon. Compared with that at 25°C, the decay rate of SARS-CoV-2 pseudovirus was significantly lower at low temperatures. Seawater preserved viral stability both at -18°C and with repeated freeze−thaw cycles compared with that in deionized water. Visible light from light-emitting diode (LED) illumination and airflow at -18°C reduced SARS-CoV-2 pseudovirus stability.ConclusionOur studies indicate that temperature and seawater in the cold chain are risk factors for SARS-CoV-2 transmission, and LED visible light irradiation and increased airflow may be used as disinfection measures for SARS-CoV-2 in the cold-chain environment.

Abstract Parental RNAi (pRNAi) is a response of RNA interference in which treated insect pests progenies showed a gene silencing phenotypes. pRNAi of CmGNA gene has been studied in Cnaphalocrocis medinalis via injection. Our results showed significant reduction in ovulation per female that was 26% and 35.26% in G1 and G2 generations, respectively. Significant reduction of hatched eggs per female were observed 23.53% and 45.26% as compared to control in G1–G2 generations, respectively. We also observed the significant variation in the sex ratio between female (40% and 53%) in G1–G2 generations, and in male (65%) in G1 generation as compared to control. Our results also demonstrated the significant larval mortality (63% and 55%) and pupal mortality (55% and 41%), and significant reduction of mRNA expression level in G1 and G2 generations. Our findings have confirmed that effectiveness of pRNAi induced silencing on the CmGNA target gene in G1–G2 generations of C. medinalis. These results suggested the potential role of pRNAi in insect pest resistance management strategies.

Objective: To analyze the differential expression and prognostic value of Mitochondrial ribosomal protein L52 (MRPL52) in hepatocellular carcinoma using bioinformatics, and to explore the prognostic value and role of the MRPL52 in the immune regulation of hepatocellular carcinoma. Methods: Hepatocellular Carcinoma Database (HCCDB) and Tumor Immune Estimation Resource (TIMER) databases were used in analyzing the differential expression of MRPL52 in hepatocellular carcinoma tissue and normal paracancerous tissues; UALCAN database was used to analyze the correlation between levels of MRPL52 expression and levels of DNA methylation vs. clinical phenotypes, including tumor grade, tumor stage, and metastasis, Kaplan–Meier plotter database was used in analyzing the relationship between MRPL52 expression and hepatocellular carcinoma survival; LinkedOmics database was used in analyzing MRPL52 co-expression genes, target miRNAs and transcription factors; GENEMANIA database was used to construct the protein interaction network; DiseaseMeth database and MEXPRESS database were used to analyze the level of MRPL52 DNA methylation and changes in methylation sites, and TIMER database was used in analyzing the relationship between MRPL52 and immune infiltration of hepatocellular carcinoma. Results: MRPL52 was highly expressed in hepatocellular carcinoma and was positively correlated with clinical phenotypes, including tumor grade, tumor stage, and distant metastasis; high expression of MRPL52 was associated with poor prognosis of hepatocellular carcinoma; co-expression analysis showed that MRPL52 co-expression genes were enriched in multiple cancer-related signal pathways, and methylation analysis showed that the DNA methylation level of MRPL52 reduced significantly in hepatocellular carcinoma. Additionally, significant changes were found in methylation sites cg07436208 and cg04556361, which were negatively correlated with the expression level of MRPL52, and K–M survival analysis showed that the cg04556361 methylation site was negatively correlated with the overall survival of hepatocellular carcinoma; MRPL52 was associated with immune cell infiltration of hepatocellular carcinoma, and Cox multivariate regression analysis showed that MRPL52 could increase the risk of overall survival (OS) by 1.435-fold in the absence of immune cells. Conclusion: The expression level of MRPL52 in patients with hepatocellular carcinoma is increased, which is related closely to poor prognosis, suggesting that MRPL52 is expected to become a prognostic marker and a new target for the treatment of hepatocellular carcinoma.

Through the application ratio of nitrogen (N), phosphorus (P) and potassium (K) in the field, L9 (33) orthogonal experimental design was used to study the effects of different N, P and K ratios on the yield and quality of blueberry fruit, aiming to optimize the amount of supplied fertilizers. The results showed that N, P and K fertilizer had different effects on fruit yield and quality, among which K fertilizer was the most important factor. Fertilization could significantly improve the yield and fruit quality of blueberry, and the average yield of fertilization treatment was 37.78% higher than that of the control group (CK). Even the treatment with the worst results F6 (N2P3K1), its single fruit weight, anthocyanins, total phenols, soluble solids and soluble protein content were 1.09, 1.32, 1.23, 1.08 and 1.21 times higher than the control (CK), respectively. Based on the comprehensive evaluation of principal component analysis and multi factor analysis of variance, the best fertilization combination for high-yield and good-quality blueberries was N1P2K2 (F2), that is, the best fertilization effect was that including N 100 g/plant, P2O5 25 g/plant, K2O 25 g/plant, applied in the form of ammonium sulfate (472 g/plant), superphosphate (41 g/plant) and potassium sulfate (40 g/plant), respectively.

Fruit color is an important economic character of blueberry, determined by the amount of anthocyanin content. Anthocyanin synthesis within the blueberry fruits is significantly affected by light. To reveal the physiological response mechanism of anthocyanin synthesis in blueberry fruits in different light intensities, four light intensities (100% (CK), 75%, 50% and 25%) were set for the 'O'Neal' southern highbush blueberry as the experimental material in our study. The relationship between endogenous hormones content, associated enzyme activities, and variations with the anthocyanin content in blueberry fruits under various light intensities during the white fruit stage (S1), purple fruit stage (S2), and blue fruit stage (S3) were studied. The results showed that adequate light could significantly promote anthocyanin synthesis in blueberry fruits (P < 0.05). Blueberry fruits had an anthocyanin content that was 1.76~24.13 times higher under 100% light intensity than it was under non-full light intensity. Different light intensities significantly affected the content of endogenous hormones and the activity of associated enzymes in anthocyanin synthesis pathway (P < 0.05). Among them, the JA (jasmonic acid) content and PAL (phenylalanine ammonia lyase) activity of fruits under 100% light intensity were 2.49%~41.83% and 2.47%~48.48% higher than those under other light intensity, respectively. And a significant correlation was found between the variations in anthocyanin content in fruits and the content or activities of JA, ABA (abscisic acid), ETH (ethylene), GA3 (gibberellin 3), IAA (indoleacetic acid), PAL, CHI (chalcone isomerase), DFR (dihydroflavonol reductase) and UFGT (UDP-glucose: flavonoid 3-glucosyltransferase) (P < 0.05). It indicated that 100% light intensity significantly promoted anthocyanin synthesis in blueberry fruits by affecting endogenous hormones content and associated enzyme activities in the anthocyanin synthesis pathway. This study will lay a foundation for further research on the molecular mechanism of light intensity regulating anthocyanin synthesis in blueberry.

Gout is a common inflammatory disease. The activation of NLRP3 inflammasome induced by monosodium urate (MSU) crystals has a critical role in gout, and its prevention is beneficial for patients. Lipoxin A4 (LXA4) is an endogenous lipoxygenase-derived eicosanoid mediator with powerful anti-inflammatory properties. However, whether LXA4 can suppress NLRP3 inflammasome activation induced by MSU crystals remains unclear. This study aimed to investigate the protective effect of LXA4 on MSU-crystal-induced NLRP3 inflammasome activation and its underlying molecular mechanisms. We found that LXA4 inhibited MSU-crystal-induced NLRP3 inflammasome activation, interleukin (IL)-1β maturation, and pyroptosis. More specifically, LXA4 suppressed the assembly of the NLRP3 inflammasome, including oligomerization and speck formation of ASC, and ASC-NLRP3 interaction. Furthermore, LXA4 suppressed oxidative stress, the upstream events for NLRP3 inflammasome activation, as evidenced by the fact that LXA4 eliminated total reactive oxygen species (ROS) generation and alleviated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and mitochondrial dysfunction. However, LXA4 also depressed the Nrf2 activation, a critical molecule in the antioxidant pathway, and then exerted an inhibitory impact on Klf9 expression and promotional impact on TXNRD2 expression, two molecules located downstream of Nrf2 in sequence. Knockdown of TXNRD2 reversed the LXA4-induced depression of ROS and NLRP3 inflammasome. Moreover, LXA4 alleviated joint inflammation and decreased the production of cleaved caspase-1 and matured IL-1β in gouty arthritis rats. Taken together, our findings demonstrate that LXA4 can attenuate MSU-crystal-induced NLRP3 inflammasome activation, probably through suppressing Nrf2 activation to increase TXNRD2 expression. The present study highlights the potential of LXA4 as an attractive new gout treatment candidate.

ObjectiveSelf-injurious behavior (SIB) is a clinically challenging problem in the general population and several clinical disorders. However, the precise molecular mechanism of SIB is still not clear. In this paper, the systematic investigation of the genesis and development of SIB is conducted based on behavioral and pathophysiology studies in mink (Neovison vison) models.MethodThe night-vision video was used to observe the mink behavior, and the duration was a month. HE stain was performed to characterize the pathology change in the brain of a mink. IHC assay was performed to conduct the protein level detection of Iba-1, p-CREB, CBP, and p300 in the brain tissues. Elisa assay was used to examine the levels of NfL and NfH in serum and CSF of mink. The qRT-PCR assay was used to detect the expression of Bcl-2, NOR1, FoxO4, c-FOS, CBP, and p300 in brain tissues. Western blot was used to detect the protein levels of p-CREB, CBP, and p300 in brain tissues. We also used Evans Blue as a tracer to detect whether the blood-brain barrier was impaired in the brain of mink.ResultThe behavioral test, histopathological and molecular biology experiments were combined in this paper, and the results showed that CBP was related to SIB. Mechanism analysis showed that the dysregulation of CBP in brain-activated CREB signaling will result in nerve damage of the brain and SIB symptoms in minks. More importantly, the CBP-CREB interaction inhibitor might help relieve SIB and nerve damage in brain tissues.ConclusionOur results illustrate that the induction of CBP and the activation of CREB are novel mechanisms in the genesis of SIB. This finding indicates that the CBP-CREB axis is critical for SIB and demonstrates the efficacy of the CBP-CREB interaction inhibitor in treating these behaviors.

Amino acid balance is central to improving the efficiency of feed protein utilization and for reducing environmental pollution caused by intensive farming. In previous studies, supplementation with limiting amino acids has been shown to be an effective means of improving animal nutrient utilization and performance. In this experiment, the effects of methionine on the apparent digestibility of nutrients, antler nutrient composition, rumen fluid amino acid composition, fecal volatile fatty acids and intestinal bacteria in antler-growing sika deer were investigated by randomly adding different levels of methionine to the diets of three groups of four deer at 0 g/day (CON), 4 g/day (LMet) and 6 g/day (HMet). Methionine supplementation significantly increased the apparent digestibility of organic matter, neutral detergent fiber (NDF) and acid detergent fiber (ADF) in the LMet group (p < 0.05). The crude protein and collagen protein of antlers were significantly higher in the LMet and HMet groups compared to the CON group and also significantly higher in the HMet group compared to the LMet group, while the calcium content of antlers was significantly lower in the HMet group (p < 0.05). Ruminal fluid free amino acid composition was altered in the three groups of sika deer, with significant changes in aspartic acid, citrulline, valine, cysteine, methionine, histidine and proline. At the phylum level, Firmicutes and Bacteroidetes were highest in the rectal microflora. Unidentified bacterial abundance was significantly decreased in the HMet group compared to the CON group. Based on the results of principal coordinate analysis (PCoA) and Adonis analysis, there was a significant difference in the composition of the intestinal flora between the CON and HMet groups (p < 0.05). At the genus level, compared with the CON group, the abundance of Rikenellaceae_RC9_gut_group and Lachnospiraceae_UCG-010 in the LMet group increased significantly (p < 0.05), the abundance of dgA-11_gut_group in the HMet group decreased significantly (p < 0.05) and the abundance of Lachnospiraceae_UCG-010, Saccharofermentans and Lachnospiraceae_NK3A20_group increased significantly. Taken together, the results showed that methionine supplementation was beneficial in increasing the feed utilization efficiency and improving antler quality in sika deer, while affecting the composition of fecal bacteria.

Abstract To explore the effects of urea dissociation on reducing false-positive results of the Elecsys HIV combi PT assay. A retrospective analysis was used to evaluate the false-positive rate of the Elecsys HIV combi PT assay. Six false-positive sera, six positive sera and six sera from patients with early HIV infection were collected. Dissociation was performed using 1 mol/L, 2 mol/L, 4 mol/L, 6 mol/L, or 8 mol/L urea, and HIV screening assay were then detected to select the appropriate concentration of urea dissociation. Next, 55 false-positive sera and 15 sera from early HIV infection were used to verify the best concentration of urea to achieve dissociation. Retrospective analysis showed that the COI of the Elecsys HIV combi PT assay in false-positive sera ranged from 1.0 to 200.0, and approximately 97.01%(227/234) of false-positive sera were in the range of 1.0–15.0. The avidity index (AI) in positive and false-positive sera decreased as the urea dissociation concentration increased. When the dissociation concentration was 6 mol/L, the AI of false-positive serum was between 0.0234 and 0.2567, and the AI of early HIV infection sera was between 0.4325 and 0.5017. The difference in AI between false-positive and positive samples was significant. When negativity was defined as an AI of less than 0.3970, the sensitivity and specificity were 100.0% and 100.0%, respectively. Urea-mediated dissociation could significantly reduce the false-positive rate of the Elecsys HIV combi PT assay with a low COI. Our findings provided a reference for distinguishing positive and false-positive of the Elecsys HIV combi PT assay.

Peel colour is an important economic trait in blueberries (Vaccinium spp.) and is determined by the composition and concentration of anthocyanins. Anthocyanin accumulation within the blueberry peel is significantly affected by light. In the present study, the response mechanism of blueberry anthocyanin synthesis to various light intensities was explored in an effort to identify candidate genes involved in anthocyanin content changes using transcriptomic analysis. The analysis results indicated that a total of 671 differential genes were found, including 53 transcription factors. Among the 16 gene families of the anthocyanin synthesis pathway, 428 genes have certain expression. A total of 6,004 transcription factors in blueberry were identified following the analysis, and divided into 58 transcription factor families of which the largest was the MYB family (510). Co-expression analysis of transcription factors and anthocyanin synthesis pathway genes revealed that 36 genes (16 families) in the anthocyanin synthesis pathway are co-expressed with 66 transcription factors. The quantitative real-time polymerase chain reaction analysis results were consistent with the transcriptomic results. Six of these genes likely play an important role in the anthocyanin synthesis pathway, and further evaluation of these candidate genes is necessary. This study provides a foundation for further research on the mechanism of light-induced anthocyanin synthesis in blueberry. Supplemental data for this article is available online at https://doi.org/10.1080/13102818.2021.1924078 .

Nearly half of human cancers harbor p53 mutations, and mutant p53 (mutp53) promotes carcinogenesis, metastasis, tumor recurrence and chemoresistance. mutp53 is observed in 30% of breast carcinomas, including triple‐negative breast cancer (TNBC), and thus mutp53 is a promising target for treatment of TNBC. In this study, we investigated the effect of a phosphatidylinositide 3 kinase/mammalian target of rapamycin dual inhibitor, NVP‐BEZ235 (BEZ235), on two TNBC cell lines with mutp53: MDA‐MB‐231 and MDA‐MB‐468. Cell growth, migration and colony‐formation abilities were detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide, scratch assay, transwell and soft agar assay, revealing that BEZ235 can inhibit the growth, migration and colony‐formation abilities of TNBC cells. In addition, BEZ235 caused degradation of mutp53 in these cells. We investigated the underlying mechanism by inhibiting proteasome function using MG132 and inhibiting autophagy using 3‐methyladenine and shRNAs. We observed that BEZ235 may induce autophagy through repression of the Akt/mammalian target of rapamycin signaling pathway. The observed interplay between mutp53 and autophagy in TNBC cells was examined further by knockdown of ATG5 and ATG7, revealing that degradation of mutp53 induced by BEZ235 may be independent of the ubiquitin–proteasome pathway and autophagy mediated by ATG5 and ATG7. Moreover, we found evidence of positive feedback between mutp53 and autophagy in TNBC cells. In conclusion, BEZ235 may exert antitumor effects against TNBC cells by targeting mutp53, and this may have implications for the development of future therapies.

Abstract Background Dihydroartemisinin (DHA), a derivate of artemisinin, is an effective antimalarial agent. DHA has been shown to exert anticancer activities to numerous cancer cells in the past few years, while the exact molecular mechanisms remain to be elucidated, especially in esophageal cancer. Methods Crystal violet assay was conducted to determine the cell viability of human esophageal cancer cell line Eca109 treated with DHA. Tumor-bearing nude mice were employed to evaluate the anticancer effect of DHA in vivo. Soft agar and crystal violet assays were used to measure the tumorigenicity of Eca109 cells. Flow cytometry was performed to evaluate ROS or cell cycle distribution. GFP-LC3 plasmids were delivered into Eca109 cells to visualize autophagy induced by DHA under a fluorescence microscope. The mRNA and protein levels of each gene were tested by qRT-PCR and western blot, respectively. Results Our results proved that DHA significantly reduced the viability of Eca109 cells in a dose- and time-dependent manner. Further investigation showed that DHA evidently induced cell cycle arrest at the G2/M phase in Eca109 cells. Mechanistically, DHA induced intracellular ROS generation and autophagy in Eca109 cells, while blocking ROS by an antioxidant NAC obviously inhibited autophagy. Furthermore, we found that telomere shelterin component TRF2 was down-regulated in Eca109 cells exposed to DHA through autophagy-dependent degradation, which could be rescued after autophagy was blocked by ROS inhibition. Moreover, the DNA damage response (DDR) was induced obviously in DHA treated cells. To further explore whether ROS or autophagy played a vital role in DHA induced cell cycle arrest, the cell cycle distribution of Eca109 cells was evaluated after ROS or autophagy blocking, and the results showed that autophagy, but not ROS, was essential for cell cycle arrest in DHA treated cells. Conclusion Taken together, DHA showed anticancer effect on esophageal cancer cells through autophagy-dependent cell cycle arrest at the G2/M phase, which unveiled a novel mechanism of DHA as a chemotherapeutic agent, and the degradation of TRF2 followed by DDR might be responsible for this cell phenotype.

Plant anthocyanin is a secondary metabolite widely distributed in the roots, stems, leaves, flowers and fruits of plants, and its synthesis is significantly affected by light intensity. To reveal the physiological response mechanism of anthocyanin synthesis in blueberry leaves at different light intensities, four light intensities (100% (CK), 75%, 50% and 25%) were set for the ‘O’Neal’ southern highbush blueberry as the experimental material in our study. The relationship between endogenous hormone contents, key enzyme activities, and variations in the anthocyanin content in blueberry leaves under various light intensities during the white fruit stage (S1), purple fruit stage (S2) and blue fruit stage (S3) of fruit development were studied. The results showed that the anthocyanin content of blueberry leaves increased first and then decreased, and decreased first and then increased with the increase in light intensity and development stage, respectively. The appropriate light intensity could significantly promote the synthesis of anthocyanin, and the anthocyanin content in leaves treated with 75% light intensity was 1.09~4.08 times that of other light intensity treatments. The content or activities of gibberellin (GA3), indoleacetic acid (IAA), jasmonic acid (JA), abscisic acid (ABA), ethylene (ETH), phenylalanine ammonia lyase (PAL), chalcone isomerase (CHI), dihydroflavonol reductase (DFR) and UDP-glucose: flavonoid 3-glucosyltransferase (UFGT) were significantly or extremely significantly correlated with the content of anthocyanin in leaves. This indicated that light intensity significantly promoted anthocyanin synthesis in blueberry leaves by affecting endogenous hormone contents and key enzyme activities in the anthocyanin synthesis pathway. This study lays a foundation for further research on the molecular mechanism of light intensity regulating anthocyanin synthesis in blueberry leaves.

Objective. To investigate the expression of Yin-Yang-1 (YY1) in esophageal carcinoma (ESCA) and its effect on glutamine metabolism in ESCA. Methods. The expression and roles of YY1 in ESCA were investigated using a series of bioinformatics databases and tools. The expression of YY1 between ESCA tissues with the corresponding adjacent tissues was validated using real-time PCR, western blot, and immunohistochemical staining method. Furthermore, the effects of YY1 on ESCC cell proliferation and migration were examined. The correlation between the YY1 and glutamine metabolism was evaluated by western blot. Results. YY1 gene was highly conserved in evolution and upregulated in ESCA tissues and ESCC cell lines (ECA109 and TE-1). In addition, YY1 may affect the level of immune cell infiltration and promote tumor cell immune escape. Functional enrichment analysis found that YY1 involved in many biological processes, such as cell division and glutathione and glutamine metabolism. After siRNA knockdown of YY1 in ECA109 and TE-1, the proliferation and the migration of ECA109 and TE-1 were suppressed. The glutamine consumption and glutamate production were significantly decreased. The protein expression of alanine-, serine-, cysteine-preferring transporter 2 (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLUD1) was significantly downregulated. Conclusion. YY1 is highly expressed in ESCA and may promote glutamine metabolism of ESCC cells, indicating it may be as a diagnostic biomarker for ESCA.

Background:TP53 family members play an indispensable role in various human cancers, while the gene expression profiles, prognostic value, and potential mechanism in esophageal cancer (ESCA) are yet unclear.Methods: The expression and roles of TP53 family members in ESCA were investigated using the Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER), Kaplan–Meier plotter, gene set enrichment analysis (GSEA), and UALCAN databases. The expression of TP53 between ESCA and the corresponding adjacent tissues was validated using qRT-PCR. Furthermore, the effects of TP53 on esophageal squamous cell carcinoma (ESCC) cell migration and proliferation were examined using the Transwell assay, scratch test, and crystal violet assay. The correlation between TP53 and mTOR pathways was evaluated by Western blotting.Results: This study showed a correlation between high mRNA expression of TP53 members (TP53, TP63, and TP73) and clinical cancer stages and nodal metastasis status in ESCA patients. Moreover, the expression of TP53 was significantly associated with the overall survival (OS) of ESCA patients. Additional experiments verified that the mRNA of TP53 was upregulated in ESCC patients. Moreover, the downregulated expression of TP53 significantly retarded ESCC cell migration and proliferation and might activate the mTOR signaling pathway and inhibit TP53-dependent autophagy.Conclusion:TP53 has a prognostic value in ESCA and may be a leading factor in promoting ESCA pathogenesis.

Objective: To elucidate the oncogenic role of human telomerase reverse transcriptase (hTERT) in esophageal squamous cancer and unravel the therapeutic role and molecular mechanism of dihydroartemisinin (DHA) by targeting hTERT.Methods: The expression of hTERT in esophageal squamous cancer and the patients prognosis were analyzed by bioinformatic analysis from TCGA database, and further validated with esophageal squamous cancer tissues in our cohort. The Cell Counting Kit-8 (CCK8) and colony formation assay were used to evaluate the proliferation of esophageal squamous cancer cell lines (Eca109, KYSE150, and TE1) after hTERT overexpression or treated with indicated concentrations of DHA. Transwell migration assay and scratch assay were employed to determine the migration abilities of cancer cells. Fluorescence microscopy and flow cytometry were conducted to measure the intracellular reactive oxygen species (ROS) levels in cancer cells after treated with DHA. Moreover, RT-PCR and Western blot were performed to test the alteration of associated genes on mRNA and protein level in DHA treated esophageal squamous cancer cell lines, respectively. Furthermore, tumor-bearing nude mice were employed to evaluate the anticancer effect of DHA in vivo.Results: We found that hTERT was significantly upregulated in esophageal squamous cancer both from TCGA database and our cohort also. Overexpression of hTERT evidently promoted the proliferation and migration of esophageal squamous cancer cells in vitro. Moreover, DHA could significantly inhibit the proliferation and migration of esophageal cancer cell lines Eca109, KYSE150, and TE1 in vitro, and significantly down-regulate the expression of hTERT on both mRNA and protein level in a time- and dose-dependent manner as well. Further studies showed that DHA could induce intracellular ROS production in esophageal cancer cells and down-regulate SP1 expression, a transcription factor that bound to the promoter region of hTERT gene. Moreover, overexpression of SP1 evidently promoted the proliferation and migration of Eca109 and TE1 cells. Intriguingly, rescue experiments showed that inhibiting ROS by NAC alleviated the downregulation of SP1 and hTERT in cells treated with DHA. Furthermore, overexpression of SP1 or hTERT could attenuate the inhibition effect of DHA on the proliferation and migration of Eca109 cells. In tumor-bearing nude mice model, DHA significantly inhibited the growth of esophageal squamous cancer xenografts, and downregulated the expression of SP1 and hTERT protein, while no side effects were observed from heart, kidney, liver, and lung tissues by HE stain.Conclusion: hTERT plays an oncogenic role in esophageal squamous cancer and might be a therapeutic target of DHA through regulating ROS/SP1 pathway.

Background: Smell and taste dysfunctions are common and have been reported as an early indicator of COVID-19. The prevalence of smell and taste dysfunctions among children with COVID-19 varies greatly across studies, which remains to be summarized quantitatively. This review aimed at examining the pooled prevalence of smell or taste dysfunctions among children with COVID-19, summarizing possible causes of the inconsistencies in the current estimates.Methods: Systematic searches of databases were conducted for literature published until 12 January 2021. Statistical analyses were performed using R software, the pooled prevalence was combined using random effects model. The Loney criteria were used for quality assessment.Results: A total of 18 eligible studies were included. The results showed that the pooled prevalence of smell dysfunction among children with COVID-19 was 15.97% (95% CI: 8.18–23.77%), the pooled prevalence of taste dysfunction among children with COVID-19 was 9.20% (95% CI: 4.25–14.16%), the pooled prevalence of smell or taste dysfunction among children with COVID-19 was 15.50% (95% CI: 10.30–20.70%) and the pooled prevalence of smell and taste dysfunction among children with COVID-19 was 20.21% (95% CI: 14.14–26.28%). Higher smell or taste dysfunction rates were associated with being female, younger age, smaller sample size, patients in Asia, and with comorbidities.Conclusions: Evidence suggests that smell or taste dysfunctions were common among children with COVID-19. Further research is needed to identify effective strategies for preventing and treating smell and taste dysfunctions among children with COVID-19.

Methionine is the first or second limiting amino acid for ruminants, such as sika deer, and has a variety of biological functions such as antioxidant activity, immune response, and protein synthesis. This study aimed to investigate the effects of methionine supplementation on antler growth, serum biochemistry, rumen fermentation, and the bacterial community of sika deer during the antler-growing period. Twelve 4-year-old male sika deer were randomly assigned to three dietary groups supplemented with 0 g/day (n = 4, CON), 4.0 g/day (n = 4, LMet), and 6.0 g/day (n = 4, HMet) methionine. No significant difference (p > 0.05) was found in the production performance between the three groups, but antler weight was higher in both the LMet and HMet groups than in the CON group. Methionine supplementation significantly increased the serum glutathione peroxidase activity (p < 0.05). The serum immunoglobulin G level was significantly higher in the HMet group than in the other two groups (p < 0.05). No significant effect was found on the apparent amino acid digestibility of the three groups, but cysteine and methionine digestibility were higher in the LMet group. The serum hydroxylysine level was significantly lower in the LMet and HMet groups, whereas the serum lysine level was significantly lower in the HMet group compared with the CON group (p < 0.05). The LMet group had the highest but a nonsignificant total volatile fatty acid content and significantly higher microbial protein content in the rumen than the CON group (p < 0.05). The phyla Bacteroidetes, Firmicutes, and Proteobacteria were dominant in the rumen of the sika deer. The principal coordinate analysis (PCoA) and analysis of similarities (ANOSIM) results showed a significant change in the bacterial composition of the three groups (p < 0.05). The relative abundance of Prevotella and Rikenellaceae-RC9 was significantly higher in the LMet group compared with the CON group and CON and HMet groups, respectively. These results revealed that methionine supplementation improved the antioxidant activity and immune status, affecting amino acid metabolism and rumen microbial composition of the sika deer.

Silk fibroin gels, formed with electric fields, have been studied and potential utility in medical materials. However, silk electrogels with controllable nanofiber network morphology have rarely been reported. In this work, low voltage electric field was developed to control the nanofiber network morphology formation and resulting electrogelation of silk fibroin aqueous solution, inducing a transition from an overall protein structure that is initially rich in random coil to one that is rich in β-sheet. Under low voltage (3–24 V), solution concentration (≤5.0 wt%), and neutral, alkaline conditions, silk fibroin fibrous electrogels were easily formed. At the same time, compression test result exhibited the compressive stress of silk fibroin fibrous electrogels was 250.17 ± 16.50 kPa at dry state, which formed from silk fibroin concentration 3.0 wt%. Moreover, the recovery rate of electrogels can reach more than 50% after 10 compression-recovery circles, exhibiting excellent flexibility. In addition, silk fibroin electrogels loaded cefixime drugs have obvious antibacterial effect against Staphylococcus aureus and Escherichia coli than commercial medical band-aids. Drug-loaded silk fibroin fibrous electrogels supported mouse embryonic fibroblasts 3 T3 cells attachment and proliferation over 7 days. This study offers an effective approach to design and synthesis of new dressings.

Understanding the impact of irrigation and fertilizer on rabbiteye blueberry (Vaccinium virgatum) physiology is necessary for its precision planting. Here, we applied varied irrigation and fertilizer under completely randomized experimental design to see its impact on the physiological characteristics and bush growth of rabbiteye blueberries. A comprehensive evaluation of the membership function was used to establish the best water-fertilizer coupling regimes. Rabbiteye blueberry enhanced the net photosynthetic rate, stomatal conductance and transpiration rate of leaf and improved its photosynthetic capacity at maximum level of irrigation water and fertilizer application (F3W4). The high fertilizer-medium water treatment (F3W3) increased leaf-soluble protein contents. The medium fertilizer-medium water treatment (F2W3, F2W2) increased leaf- soluble sugar, superoxide dismutase, and chlorophyll contents; decreased the malondialdehyde content; and enhanced leaf resistance and metabolism. It also promoted the growth of flower buds and new shoots. Combined membership function and cluster analyses revealed that the optimal water and fertilizer conditions for promoting rabbiteye blueberry plant growth were the medium fertilizer-medium water [(NH4)2SO4:Ca(H2PO4)2:K2SO4 at 59:10:20 g plant-1; 2.5 L water plant-1], medium fertilizer-medium-high water [(NH4)2SO4:Ca(H2PO4)2:K2SO4 at 59:10:20 g plant-1; 3.75 L water plant-1], and high fertilizer-medium-high water [(NH4)2SO4:Ca(H2PO4)2:K2SO4 at 118:20:40 g plant-1; 3.75 L water plant-1] treatments. The findings of this study could be used in improving the precision and efficacy of rabbiteye blueberry planting in Guizhou, China. Such an approach can increase the productivity and profitability for local fruit farmers.

We aimed to determine whether the average mean arterial pressure (aMAP) in the first 24 hours of hospital admission is useful in predicting short-term outcomes of patients with intermediate- and high-risk pulmonary embolism (PE). We conducted a single-center retrospective study. From May 2012 to April 2019, 122 patients with intermediate- and high-risk PE were included. The primary outcome was in-hospital mortality. The secondary outcome was adverse events. Receiver operating characteristic (ROC) curves and cutoff values for aMAP predicting in-hospital death were computed. According to cutoff values, we categorized 5 groups defined as follows: group 1: aMAP < 70 mm Hg; group 2: 70 mm Hg ≤ aMAP < 80 mm Hg; group 3: 80 mm Hg ≤ aMAP < 90 mm Hg; group 4: 90 mm Hg ≤ aMAP

Background/Aims: MicroRNAs (miRNAs) play a crucial role in erythropoiesis. MiR-23a∼27a∼24-2 clusters have been proven to take part in erythropoiesis via some proteins. CDC25B (cell division control Cdc2 phosphostase B) is also the target of mir-27a; whether it regulates erythropoiesis and its mechanism are unknown. Methods: To evaluate the potential role of miR-27a during erythroid differentiation, we performed miR-27a gain- and loss-of-function experiments on hemin-induced K562 cells. We detected miR-27a expression after hemin stimulation at different time points. At the same time, the γ-globin gene also was measured via real-time PCR. According to the results of the chips, we screened the target protein of miR-27a through a dual-luciferase reporter assay and identified it via Western blot analyses. To evaluate the function of CDC25B, benzidine staining and flow cytometry were employed to detect the cell differentiation and cell cycle. Results: We found that miR-27a promotes hemin-induced erythroid differentiation of human K562 cells by targeting cell division cycle 25 B (CDC25B). Overexpression of miR-27a promotes the differentiation of hemin-induced K562 cells, as demonstrated by γ-globin overexpression. The inhibition of miR-27a expression suppresses erythroid differentiation, thus leading to a reduction in the γ-globin gene. CDC25B was identified as a new target of miR-27a during erythroid differentiation. Overexpression of miR-27a led to decreased CDC25B expression after hemin treatment, and CDC25B was up-regulated when miR-27a expression was inhibited. Moreover, the inhibition of CDC25B affected erythroid differentiation, as assessed by γ-globin expression. Conclusion: This study is the first report of the interaction between miR-27a and CDC25B, and it improves the understanding of miRNA functions during erythroid differentiation.

Abstract Background The bronchial epithelium serves as the first defendant line of host against respiratory inhaled pathogens, mainly through releasing chemokines (e.g. interleukin-8 (IL-8), interferon-induced protein 10 (IP-10) etc.) responsible for neutrophil or lymphocyte recruitment to promote the clearance of inhaled pathogens including Streptococcus pneumoniae (S. pneumoniae). Previous studies have shown that IL-8 expression is induced by pneumococcal virulence factors (e.g. pneumolysin, peptidoglycan-polysaccharides, pneumococcal surface protein A (PspA) etc.), which contributes to the pathogenesis of pneumonia. Whether other pneumococcal virulence factors are involved in inducing chemokines expression in epithelium is still unknown. Results We studied the effect of PepO, a widely expressed and newly discovered pneumococcal virulence protein, on the release of proinflammatory cytokines, IL-8 and IP-10, from human bronchial epithelial cell line BEAS-2B and identified the relevant signaling pathways. Incubation of BEAS-2B with PepO resulted in increased synthesis and release of IL-8 and IP-10 in a dose and time independent manner. We also detected the increased and sustained expression of TLR2 and TLR4 transcripts in BEAS-2B stimulated by PepO. PepO activation leaded to the phosphorylation of MAPKs, Akt and p65. Pharmacologic inhibitors of MAPKs, PI3K and IκB-α phosphorylation attenuated IL-8 release, while IP-10 production was just suppressed by inhibitors of IκB-α phosphorylation, PI3K and P38 MAPK. Conclusion These results suggest that PepO enhances IL-8 and IP-10 production in BEAS-2B in a MAPKs-PI3K/Akt-p65 dependent manner, which may play critical roles in the pathogenesis of pneumonia.

PARP1, in addition to its role in DNA repair, has a role in regulating gene transcription via PARylation of target proteins. Here the authors show that HuR is targeted after lipopolysaccharide exposure to regulate the inflammatory gene expression at post-transcriptional level.

Currently, no therapeutic options exist for castration-resistant prostate cancer (CRPC) patients who have developed resistance to the second generation anti-androgen receptor (AR) axis therapy. Here we report that co-deletion of Pten and p53 in murine prostate epithelium, often observed in human CRPC, leads to AR-independent CRPC and thus confers de novo resistance to second generation androgen deprivation therapy (ADT) in multiple independent yet complementary preclinical mouse models. In contrast, mechanism-driven co-targeting hexokinase 2 (HK2)-mediated Warburg effect with 2-deoxyglucose (2-DG) and ULK1-dependent autophagy with chloroquine (CQ) selectively kills cancer cells through intrinsic apoptosis to cause tumor regression in xenograft, leads to a near-complete tumor suppression and remarkably extends survival in Pten−/p53-deficiency-driven CRPC mouse model. Mechanistically, 2-DG causes AMPK phosphorylation, which in turn inhibits mTORC1-S6K1 translation signaling to preferentially block anti-apoptotic protein MCL-l synthesis to prime mitochondria-dependent apoptosis while simultaneously activates ULK1-driven autophagy for cell survival to counteract the apoptotic action of anti-Warburg effect. Accordingly, inhibition of autophagy with CQ sensitizes cancer cells to apoptosis upon 2-DG challenge. Given that 2-DG is recommended for phase II clinical trials for prostate cancer and CQ has been clinically used as an anti-malaria drug for many decades, the preclinical results from our proof-of-principle studies in vivo are imminently translatable to clinical trials to evaluate the therapeutic efficacy by the combination modality for a subset of currently incurable CRPC harboring PTEN and TP53 mutations.

The serological detection of antibodies to Treponema pallidum is essential to the diagnosis of syphilis. However, for the presence of cross-reaction, the specific antibody tests [e.g., enzyme-linked immunosorbent assay (ELISA)] always have false-positive results. In this study, we derived and validated the dissociation of urea in an attempt to alleviate the situation of false-positive antibodies to T. pallidum detected by ELISA. Six serum samples that were false-positive antibodies to T. pallidum detected by ELISA, and 16 control serum samples (8 sera positive for both specific IgG and IgM, and 8 IgG-positive and IgM-negative sera) were collected to select the appropriate dissociated concentration and time of urea. Our goal was to establish improved an ELISA method based on the original detection system of ELISA. The sensitivity of the improved ELISA was evaluated by 275 serum samples with class IgM-positive antibodies to T. pallidum. At 6 mol/L with 10 minutes dissociation of urea, 6 samples with false-positive antibodies to T. pallidum were converted to negative, and compared with true-positive antibodies to T. pallidum. The sensitivity of the improved ELISA was 100% by detecting the class IgM-positive antibodies to T. pallidum in sera of patients with syphilis. Considering the importance at the diagnosis of syphilis, antibodies to T. pallidum in serum samples should be retested by the improved ELISA method to avoid false-positive results.

Accumulating evidence suggests that codeletion of the tumor suppressor genes Pten and p53 plays a crucial role in the development of castration-resistant prostate cancer in vivo. However, the molecular mechanism underlying Pten-/p53-deficiency-driven prostate tumorigenesis remains incompletely understood. Building upon insights gained from our studies with Pten-/p53-deficient mouse embryonic fibroblasts (MEFs), we report here that hexokinase 2 (HK2) is selectively upregulated by the combined loss of Pten and p53 in prostate cancer cells. Mechanistically, Pten deletion increases HK2 mRNA translation through the activation of the AKT-mTORC1-4EBP1 axis, and p53 loss enhances HK2 mRNA stability through the inhibition of miR143 biogenesis. Genetic studies demonstrate that HK2-mediated aerobic glycolysis, known as the Warburg effect, is required for Pten-/p53-deficiency-driven tumor growth in xenograft mouse models of prostate cancer. Our findings suggest that HK2 might be a therapeutic target for prostate cancer patients carrying Pten and p53 mutations.

High-altitude deacclimatization syndrome (HADAS) is emerging as a severe public health issue that threatens the quality of life of individuals who return to lower altitude from high altitude. In this study, we measured serum levels of SOD, MDA, IL-17A, IL-10, TNF-α, and HADAS score in HADAS subjects at baseline and 50th and 100th days and to evaluate the relationship between interleukins, including IL-17A, and HADAS. Our data showed that and the serum IL-17A levels and HADAS score decreased over time in the HADAS group, and serum IL-17A levels were significantly higher in the HADAS group at baseline and 50th day compared with controls (p

Nature Communications 8 Article number:14632 (2017); Published: 8 March 2017; Updated: 31 March 2017 The original version of this Article contained an error in the spelling of post-transcriptional in the title of the paper. This has now been corrected in both the PDF and HTML versions of the Article.