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Plant adaptation to drought stress is essential for plant survival and crop yield. Recently, harnessing drought memory, which is induced by repeated stress and recovery cycles, was suggested as a means to improve drought resistance at the transcriptional level. However, the genetic mechanism underlying drought memory is unclear. Here, we carried out a quantitative analysis of alternative splicing (AS) events in rice memory under drought stress, generating 12 transcriptome datasets. Notably, we identified exon skipping (ES) as the predominant AS type (>80%) in differential alternative splicing (DAS) in response to drought stress. Applying our analysis pipeline to investigate DAS events following drought stress in six other plant species revealed variable ES frequencies ranging from 9.94% to 60.70% depending on the species, suggesting that the relative frequency of DAS types in plants is likely to be species-specific. The dinucleotide sequence at AS splice sites in rice following drought stress was preferentially GC-AG and AT-AC. Since U12-type splicing uses the AT-AC site, this suggests that drought stress may increase U12-type splicing, and thus increase ES frequency. We hypothesize that multiple isoforms derived from exon skipping may be induced by drought stress in rice. We also identified 20 transcription factors and three highly connected hub genes with potential roles in drought memory that may be good targets for plant breeding.

Long-chain non-coding RNA ASB16-AS1 has been proven to be an oncogene for many cancer types. However, the relationship between ASB16-AS1 and immunity is still under studied. This study aims to explore the expression and prognostic potential of ASB16-AS1, and to visualize the relationship between ASB16-AS1 expression and immune infiltration in pan-cancer. We clarified ASB16-AS1 expression patterns in pan-cancer and its relationship with prognosis through multi-platform and multi-database sources (TCGA, GEO, GTEx, ArrayExpress, and SRA), and verified the function of ASB16-AS1 in liver hepatocellular carcinoma (LIHC). Then, a variety of immune cell content evaluation methods were used to mutually verify the correlation between ASB16-AS1 and immune infiltration. Finally, the relationships between ASB16-AS1 and some molecular characteristics (immune checkpoints, tumor mutation burden, microsatellite instability, oncogenic signaling pathways) were further explored. In terms of comprehensive analysis, compared with non-tumor tissues, ASB16-AS1 was highly expressed in tumor tissues, and indicated the value of poor prognosis in multiple cancer types. Functional assays, such as CCK8 assay, transwell assay and wound scratch assay, verified that high ASB16-AS1 expression promoted tumor progression in LIHC. ASB16-AS1 was positively correlated with B cells, T cell CD4+ and T cell CD8+ in most cancer types, and negatively correlated with macrophages, dendritic cells and neutrophils in some cancer types, especially in neutrophils. In addition, there were different interaction modes between ASB16-AS1 and molecular features, such as the relationship with oncogenic signaling pathways, showing that the high ASB16-AS1 expression was related to alterations in oncogenic signaling pathways. Our study emphasizes that ASB16-AS1 is a potential pan-cancer prognostic marker, whichs is associated with the immune infiltration in multiple cancer types.

The biological mechanism by which maternal undernutrition increases the metabolic disorder risk of skeletal muscles in offspring is not fully understood. We hypothesize that maternal intake restriction influences metabolic signals in the skeletal muscles of offspring via a glucagon-mediated pathway. Twenty-four pregnant goats were assigned to the control group (100% of the nutrients requirement, n = 12) and restricted group (60% of the control feed allowance from pregnant days 45 to 100, n = 12). Blood and Longissimus thoracis muscle were sampled from dams (100 d of gestation), fetuses (100 d of gestation), and kids (90 d after birth) in each group. The data were analyzed using the linear MIXED model, with the multiple comparison method of SIDAK applied. Intake restriction reduced (P

Tongue squamous cell carcinoma (TSCC) is the most common oral cavity malignancy. The role of the microbial community in TSCC development and progression is unclear. In the present study, 23 patients with TSCC were recruited. Tissue DNA was extracted from cancer and paracancerous normal tissues from all participants. Next-generation 16S rDNA amplicon sequencing and functional prediction were applied for taxonomic analysis. Alpha diversity measurements using the Shannon and Simpson diversity indexes indicated a significant increase in the microbiotic diversity of cancer samples (Shannon index: P = 0.001, Simpson index: P = 0.015); otherwise, no differences were found when using observed operational taxonomic units (OTUs) and Chao1 index (observed OTUs: P = 0.261, Chao1 index: P = 0.054). The dominant phyla of the microbiota included Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, and Fusobacteria. Multivariate analysis of variance (Adonis) and nonparametric analysis of similarities (ANOSIM) based on unweighted unifrac distances demonstrated differences in the bacterial community structure between the two groups (P = 0.001 for Adonis, P = 0.001 for ANOSIM). Compared with the normal samples, Neisseria, Streptococcus, and Actinomyces levels decreased significantly in cancer samples. Co-occurrence network analysis implied that the bacterial community in cancer was more conserved than that in normal tissue. Matched-pair analysis of cancer and control samples revealed a significant alteration in the relative abundance of specific taxa. These findings will enrich our knowledge of the association between the oral microbial community and TSCC. Further experiments should investigate the potential carcinogenic mechanism of microbial community alterations in TSCC. • Microbial community role in tongue squamous cell carcinoma. • Significant alteration of microbiome found between cancer and normal tissues. • Microbial community alteration and potential carcinogenic mechanism.

Erwinia amylovora causes fire blight on rosaceous plants. One of the major entry points of E. amylovora into hosts is flowers, where E. amylovora proliferates epiphytically on stigmatic and hypanthium surfaces and, subsequently, causes endophytic infection at the hypanthium. The type III secretion system (T3SS) is an important virulence factor in E. amylovora. Although the role of T3SS during endophytic infection is well characterized, its expression during epiphytic colonization and role in the subsequent infection is less understood. Here, we investigated T3SS gene expression in epiphytic E. amylovora on stigma and hypanthium of apple flowers under different relative humidities (RH). On stigma surfaces, T3SS was expressed in a high percentage of E. amylovora cells, and its expression promoted epiphytic growth. On hypanthium surfaces, however, T3SS was expressed in fewer E. amylovora cells than on the stigma, and displayed no correlation with epiphytic growth, even though T3SS expression is essential for infection. E. amylovora cells grown on stigmatic surfaces and then flushed down to the hypanthium displayed a higher level of T3SS expression than cells grown on the hypanthium surface alone. Furthermore, E. amylovora cells precultured on stigma had a higher potential to infect flowers than E. amylovora cells precultured in a T3SS-repressive medium. This suggests that T3SS induction during the stigmatic epiphytic colonization may be beneficial for subsequent infection. Finally, epiphytic expression of T3SS was influenced by RH. Higher percentage of stigmatic E. amylovora cells expressed T3SS under high RH than under low RH. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Background Norovirus (NoV) is the main cause of non-bacterial acute gastroenteritis (AGE) outbreaks worldwide. From September 2015 through August 2018, 203 NoV outbreaks involving 2500 cases were reported to the Shenzhen Center for Disease Control and Prevention. Methods Faecal specimens for 203 outbreaks were collected and epidemiological data were obtained through the AGE outbreak surveillance system in Shenzhen. Genotypes were determined by sequencing analysis. To gain a better understanding of the evolutionary characteristics of NoV in Shenzhen, molecular evolution and mutations were evaluated based on time-scale evolutionary phylogeny and amino acid mutations. Results A total of nine districts reported NoV outbreaks and the reported NoV outbreaks peaked from November to March. Among the 203 NoV outbreaks, 150 were sequenced successfully. Most of these outbreaks were associated with the NoV GII.2[P16] strain (45.3%, 92/203) and occurred in school settings (91.6%, 186/203). The evolutionary rates of the RdRp region and the VP1 sequence were 2.1 × 10–3 (95% HPD interval, 1.7 × 10–3–2.5 × 10–3) substitutions/site/year and 2.7 × 10–3 (95% HPD interval, 2.4 × 10–3–3.1 × 10–3) substitutions/site/year, respectively. The common ancestors of the GII.2[P16] strain from Shenzhen and GII.4 Sydney 2012[P16] diverged from 2011 to 2012. The common ancestors of the GII.2[P16] strain from Shenzhen and previous GII.2[P16] (2010–2012) diverged from 2003 to 2004. The results of amino acid mutations showed 6 amino acid substitutions (*77E, R750K, P845Q, H1310Y, K1546Q, T1549A) were found only in GII.4 Sydney 2012[P16] and the GII.2[P16] recombinant strain. Conclusions This study illustrates the molecular epidemiological patterns in Shenzhen, China, from September 2015 to August 2018 and provides evidence that the epidemic trend of GII.2[P16] recombinant strain had weakened and the non-structural proteins of the recombinant strain might have played a more significant role than VP1.

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.

Background Hepatocellular carcinoma (HCC) remains one of the most common malignant neoplasms. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a key role in the lipid remodelling and is correlated with various neoplasms. Nonetheless, the biological functions and molecular mechanisms of LPCAT1 underlying HCC remain obscure. Methods In the present study, we investigated the role of LPCAT1 in the progression of HCC. In-house RT-qPCR, tissue microarrays, and immunohistochemistry were performed to detect the expression levels and the clinical value of LPCAT1 in HCC. External datasets were downloaded to confirm the results. Proliferation, migration, invasiveness, cell cycle, and apoptosis assays were conducted to reveal the biological effects LPCAT1 has on SMMC-7721 and Huh7 cells. HCC differentially expressed genes and LPCAT1 co-expressed genes were identified to explore the molecular mechanisms underlying HCC progression. Results LPCAT1 showed upregulated expression in 3715 HCC specimens as opposed to 3105 non-tumour specimens. Additionally, LPCAT1 might be an independent prognostic factor for HCC. LPCAT1-knockout hampered cellular proliferation, migration, and metastasis in SMMC-7721 and Huh7 cells. More importantly, the cell cycle and chemical carcinogenesis were the two most enriched signalling pathways. Conclusions The present study demonstrated that increased LPCAT1 correlated with poor prognosis in HCC patients and fuelled HCC progression by promoting cellular growth, migration, and metastasis.

Endemic selenium (Se) deficiency is a major worldwide nutritional challenge. Organic Se can be synthesized through physical and chemical methods that are conducive to human absorption, but its high production cost and low output cannot meet the actual demand for Se supplementation. Some microbes are known to convert inorganic Se into organic forms of high nutritional value and Se-enriched probiotics are the main representatives. The aim of the present review is to describe the characteristics of Se-enriched yeast, lactic acid bacteria, bifidobacteria and discuss their Se enrichment mechanisms. Se products metabolized by Se-enriched probiotics have been classified, such as Se nanoparticles (SeNPs) and selenoprotein, and their bioactivities have been assessed. The factors affecting the Se enrichment capacity of probiotics and their application in animal feed, food additives, and functional food production have been summarized. Moreover, a brief summary and the development of Se-enriched probiotics, particularly their potential applications in the field of biomedicine have been provided. In conclusion, Se-enriched probiotics not just have a wide range of applications in the food industry but also have great potential for application in the field of biomedicine in the future.

Background The antimicrobial peptide LL37 is produced by white blood cells (mainly neutrophils) and various epithelial cells, and has the outstanding advantages of participating in immune regulation, causing chemotaxis of immune cells and promoting wound healing. However, the central domain of LL37 needs to be improved in terms of antimicrobial activity. Results In this study, the amino acid substitution method was used to improve the antimicrobial activity of the LL37 active center, and a dimeric design with a better selection index was selected. A flexible linker was selected and combined with the 6 × His-SUMO tag and LG was successfully expressed using Pichia pastoris as a host. Recombinant LG displayed strong antimicrobial activity by destroying the cell membrane of bacteria but had low hemolytic activity. In addition, compared with monomeric peptide FR, rLG had improved ability to tolerate salt ions. Conclusion This research provides new ideas for the production of modified AMPs in microbial systems and their application in industrial production.

Human serum albumin (HSA) is a non-glycosylated, negatively charged, single-chain polypeptide composed of 585 amino acid residues with a relative molecular mass of 66.438 kD. It is synthesized by the liver at a rate of approximately 200 mg·kg−1·day−1, with a half-life of 21 days, and subjected to catabolism in the muscles, liver, and kidneys at a rate of 4% per day.[1] Albumin, accounting for 60% of the total plasma protein, has various physiological functions,[2] such as maintaining 70% to 80% of effective plasma colloid osmotic pressure, coordinating vascular endothelial integrity, anti-oxidant and anti-inflammatory activities, maintaining the acid-base balance, and participating in the transport, distribution, and metabolism of a variety of endogenous and exogenous substances. The normal concentration of plasma albumin is 35 to 50 g/L. In clinical practice, hypoalbuminemia often occurs because of reduced albumin synthesis due to liver dysfunction, redistribution of serum albumin due to capillary leakage, or increased loss via the intestinal and renal routes. Hypoalbuminemia (defined as a serum albumin concentration less than 35 g/L) reportedly has an incidence of 24% to 87% in critically ill patients,[3] while severe hypoalbuminemia (a serum albumin concentration less than 25 g/L) has an incidence of 5.0–9.6%.[4] Hypoalbuminemia is an independent risk factor for increased short- and long-term mortality and an increased incidence of acute kidney injury (AKI) in patients with acute conditions such as trauma, cardiogenic shock, and sepsis.[5] A meta-analysis showed that for every 10 g/L decrease in the serum albumin concentration in critically ill patients, there was a 137% increase in in-hospital mortality, an 89% increase in the incidence of comorbidities, and a 72% increase in the length of hospital stay.[6] Hypoalbuminemia can also alter the pharmacokinetics of antibiotics, leading to either insufficient or excessively high blood concentrations, thereby resulting in treatment failure or excessive toxicity.[7] HSA is mainly used for fluid resuscitation and the treatment of hypoproteinemia in critically ill patients.[2] Existing studies have shown controversial results regarding whether the use of albumin in critically ill patients improves their clinical prognosis.[8] Albumin consumption varies greatly among countries,[9] and its inappropriate use is frequently seen, with 40% to 90% of reported HSA applications failing to follow clinical guidelines.[10] A tertiary hospital in China reported that hypoproteinemia was the most common indication for the use of HSA (35.6%); however, it was also used in 11.8% of patients with serum albumin concentrations more than 40 g/L. The reason for its use was not documented in 22% of cases.[11] In clinical practice, guidelines and consensus are lacking regarding the selection of HSA concentration, the timing of administration, dosage, and target concentration. Inappropriate use of HSA will cause adverse effects and increase medical costs inevitably, whereas guidance from clinical pharmacists or hospital standards can help reduce inappropriate HSA use by 30% and decrease medical costs without affecting patient prognosis.[12] To further strengthen the standardized application of HSA in critically ill patients and achieve optimal clinical outcomes, the Chinese Society of Critical Care Medicine convened a panel of relevant experts who reviewed and summarized data on the clinical use of HSA, outlined 11 relevant clinical problems, and formulated the “Expert Consensus on the Use of Human Serum Albumin in Critically Ill Patients” using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Hepatoblastoma is a kind of extreme malignancy frequently diagnosed in children. Although surgical resection is considered as the first-line treatment for hepatoblastoma, a relatively large population of patients have lost the preferred opportunity for surgery. Administration of locoregional ablation enables local tumor control but with the deficiency of insufficient ablation, residual tumor, and rapid progression. In this study, we integrated 219 hepatoblastoma and 121 non-cancer liver tissues to evaluate the expression of NR2F6, from which a higher NR2F6 level was found in hepatoblastoma compared with non-cancer livers with a standard mean difference (SMD) of 1.04 (95% CI: 0.79, 1.29). The overexpression of NR2F6 also appeared to be an efficient indicator in distinguishing hepatoblastoma tissues from non-cancer liver tissues from the indication of a summarized AUC of 0.90, with a pooled sensitivity of 0.76 and a pooled specificity of 0.89. Interestingly, nude mouse xenografts provided direct evidence that overexpressed NR2F6 was also detected in residual tumor compared to untreated hepatoblastoma. Chromatin immunoprecipitation-binding data in HepG2 cells and transcriptome analysis of HepG2 xenografts were combined to identify target genes regulated by NR2F6. We finally selected 150 novel target genes of NR2F6 in residual tumor of incomplete ablation, and these genes appeared to be associated with the biological regulation of lipid metabolism-related pathway. Accordingly, targeting NR2F6 holds a therapeutic promise in treating residual recurrent hepatoblastoma after incomplete ablation., GRAPHICAL ABSTRACT

BACKGROUND A twin pregnancy can carry greater risks than singleton pregnancies. About 60 in 100 twin pregnancies result in spontaneous birth before 37 wk, which is associated with several complications in the premature babies. Clinical detection of biomarkers may help to predict the possibility of premature birth so that corresponding interventions can be given to the pregnant women in a timely manner, in order to reduce the risk of preterm birth and improve the outcomes of the newborn infants. AIM To explore the clinical value of transvaginal ultrasound measurement of cervical length combined with insulin-like growth factor binding protein-1 (IGFBP-1) hyperphosphorylation in cervical secretions as predictors of preterm delivery in twin pregnancies. METHODS A total of 254 pregnant women with twin pregnancies, who were admitted to Hainan General Hospital and underwent maternity examination, were selected as the study subjects from January 2015 to December 2018. All participants received transvaginal ultrasound measurement of cervical length and phosphorylated IGFBP-1 (phIGFBP-1) test between 24 and 34 wk gestation. The pregnancy outcomes were analyzed. RESULTS Of the women with a positive phIGFBP-1 test result, preterm birth rate was higher in those with a cervical length ≤ 25 mm than those with a cervical length > 25 mm (all P < 0.05). Similarly, in women with a negative phIGFBP-1 test result, preterm birth rate was higher in those with a cervical length ≤ 25 mm than those with a cervical length > 25 mm (all P < 0.05). The sensitivity, specificity, and positive and negative predictive values of the phIGFBP-1 test combined with the cervical length test were 95.71%, 91.21%, 95.12% and 92.22%, respectively, for the prediction of preterm birth. CONCLUSION Cervical length combined with phIGFBP-1 tests is of value for the prediction of outcomes of preterm delivery in twin pregnancies.

The BCL-2 family of proteins (including the prosurvival proteins BCL-2, BCL-XL, and MCL-1) is an important target for the development of novel anticancer therapeutics. Despite the challenges of targeting protein-protein interaction (PPI) interfaces with small molecules, a number of inhibitors (called BH3 mimetics) have entered the clinic and the BCL-2 inhibitor, ABT-199/venetoclax, is already proving transformative. For BCL-XL, new validated chemical series are desirable. Here, we outline the crystallography-guided development of a structurally distinct series of BCL-XL/BCL-2 inhibitors based on a benzoylurea scaffold, originally proposed as α-helix mimetics. We describe structure-guided exploration of a cryptic "p5" pocket identified in BCL-XL. This work yields novel inhibitors with submicromolar binding, with marked selectivity toward BCL-XL. Extension into the hydrophobic p2 pocket yielded the most potent inhibitor in the series, binding strongly to BCL-XL and BCL-2 (nanomolar-range half-maximal inhibitory concentration (IC50)) and displaying mechanism-based killing in cells engineered to depend on BCL-XL for survival.

Based on a three-month toll transaction data set that includes an anonymized unique identifier for each vehicle, this paper presents an in-depth analysis of traffic volumes and tolls on the I-66 High-Occupancy Toll (HOT) express lanes in Northern Virginia. The unique identifiers allow quantification of how frequently each vehicle travels through the corridor. Vehicles observed in selected time intervals are categorized into frequent and non-frequent groups based on the total number of trips made by each vehicle. For the morning commute, the analyses show that those traveling frequently on the HOT lanes are more sensitive to high tolls and typically travel earlier in the morning to avoid higher tolls. In other words, when tolls are relatively high (e.g., over $20), the fraction of frequent users in the traffic is much smaller as compared with that of non-frequent users (e.g., 25% versus 75%). To estimate how much toll the HOT-lane users are paying per unit of travel time saved, that is, value of travel time saving (VTTS), speeds on alternative routes parallel to the I-66 corridor are computed from probe data and compared with those on I-66 express lanes. The results show that the mean VTTS is $45.37 and $61.78 for frequent and non-frequent users, respectively, during the morning peak period. Whereas for the afternoon peak, the mean VTTS is $38.14 and $37.64 for frequent and non-frequent users. The implications of the difference in these value of time distributions for dynamic tolling are discussed.

There is emerging evidence that dysregulation of long non-coding RNAs (lncRNAs) is associated with hepatocellular carcinoma (HCC). Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) functions as an oncogenic regulator in various malignancies. Nonetheless, the potential role of ZEB1-AS1 in HCC remains poorly elucidated. Herein, qRT-PCR was employed for examining ZEB1-AS1, miR-299-3p and E2F transcription factor 1 (E2F1) mRNA expressions in HCC cells and tissues. MTT assay was performed to evaluate cell proliferation. Transwell assay was utilized for evaluating cancer cell migration and invasion. Western blot was employed for measuring E2F1 protein expression. What’s more, dual-luciferase reporter assay was utilized for verifying the targeting relationships between ZEB1-AS1 and miR-299-3p, as well as E2F1 and miR-299-3p. It was demonstrated that, in HCC tissues and cells, ZEB1-AS1 expression was markedly increased, and meanwhile, its high expression level is related to the unfavourable clinicopathologic indicators. ZEB1-AS1 overexpression facilitated HCC cell proliferation, migration and invasion, while its knockdown led to the opposite effects. In terms of mechanism, we discovered that ZEB1-AS1 could decoy miR-299-3p and upregulate E2F1 expression. This work reveals the functions and mechanism of ZEB1-AS1 in HCC tumourigenesis and progression, which provides novel biomarkers and therapeutic targets for HCC.

Grass carp hemorrhagic disease is a fatal disease caused by the grass carp reovirus (GCRV). The aberrant regulation of transcripts has been implicated in many types of diseases. In the present study, we characterized mRNA and miRNA transcriptomes of different virulent GCRVs using RNA sequencing (RNA-Seq). One hundred eighteen miRNAs were identified as being differentially expressed between different virulent viruses in grass carp fibroblasts. Eight miRNAs were selected to verify the RNA-Seq results using RT-PCR and mRNA methods. In total, 996 differentially expressed mRNA genes were identified in grass carp fibroblasts, while 901 miRNA-mRNA target pairs were observed to be inversely regulated in grass carp fibroblasts. Integrated mRNA/miRNA expression profiling analysis results showed that the most influenced processes were the immune response and cell death. Three miRNAs were shown to exhibit the same expression patterns when two different methods were used and had important functions during viral infection. These results provide insights into the miRNA-mediated regulation of mRNA and valuable resources on transcript variation and regulation during GCRV infection, which are potentially useful for mechanistic and drug studies.

The fall armyworm (FAW), Spodoptera frugiperda Smith (Lepidoptera: Noctuidae) is an important agricultural pest that invaded China in the middle of December 2018. As a polyphagous pest, FAW is identified as a serious threat to agricultural production and food security in China. Pepper (Capsicum annuum L.), tomato (Solanum lycopersicum Mill.) and eggplant (Solanum melongena L.) are three of dominant solanaceous vegetables of this country. To our knowledge, the effects of these plants on the performances of FAW have not been well studied. In this study we assessed the fitness of this pest to these three plants. Results showed that FAW can complete its life cycle when fed with tomato and pepper, but not on eggplant. The population parameters of FAW fed with maize (Zea mays L.) and the three solanaceous vegetables were compared using the age-stage, two-sex life table method. Developmental duration was significantly different in the larval stage, but not in the pupae stage. FAW fed with pepper had the longest pre-adult period (41.73 d) and the lightest pupal weight (0.1134 g); the survival rate was lower than FAW fed with tomato. Significant differences were observed in the mean fecundity of female, with the highest (943.95 eggs) laid by FAW fed with tomato. FAW had the shortest mean generation time (T), the highest intrinsic rate of increase (r) and finite rate of increase (λ) on maize, and the highest net reproductive rate (R0) on tomato. Overall, FAW fitness on the three solanaceous vegetables was: tomato>pepper>eggplant. This study provides the foundation for further assessment of FAW risk to solanaceous vegetables and for establishing corresponding control strategies in China.

Camptotheca Decaisne, an endemic genus with three species confined in central and southern China, is medically important for its anticancer effects. Fossil records indicate extinct genera Amersinia...

N6-methyladenosine (m6A), and its reader protein YTHDF1, play a pivotal role in human tumorigenesis by affecting nearly every stage of RNA metabolism. Autophagy activation is one of the ways by which cancer cells survive hypoxia. However, the possible involvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma (HCC). In this study, specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing, -knockout, and -knockdown HCC cells, HCC organoids, and HCC patient-derived xenograft (PDX) murine models. YTHDF1 expression and hypoxia-induced autophagy were significantly correlated in vitro; significant overexpression of YTHDF1 in HCC tissues was associated with poor prognosis. Multivariate cox regression analysis identified YTHDF1 expression as an independent prognostic factor in patients with HCC. Multiple HCC models confirmed that YTHDF1 deficiency inhibited HCC autophagy, growth, and metastasis. Luciferase reporter assays and chromatin immunoprecipitation demonstrated that HIF-1α regulated YTHDF1 transcription by directly binding to its promoter region under hypoxia. The results of methylated RNA immunoprecipitation sequencing, proteomics, and polysome profiling indicated that YTHDF1 contributed to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modified ATG2A and ATG14 mRNA, thus facilitating autophagy and autophagy-related malignancy of HCC. Taken together, HIF-1α-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent manner. Our findings suggest that YTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.

The living fossil Craigia consists only two species Craigia yunnanensis W.W. Smith et W.E. Evans and Craigia kwangsiensis H.H. Hsue, endemic to East Asia. Craigia is a typical palaeoendemic genus, ...

Background The mechanism of body growth in mammals is poorly understood. Here, we investigated the regulatory networks involved in body growth through transcriptomic analysis of pituitary and epiphyseal tissues of smaller sized Debao ponies and Mongolian horses at the juvenile and adult stages. Results We found that growth hormone receptor (GHR) was expressed at low levels in long bones, although growth hormone (GH) was highly expressed in Debao ponies compared with Mongolian horses. Moreover, significant downregulated of the GHR pathway components m-RAS and ATF3 was found in juvenile ponies, which slowed the proliferation of bone osteocytes. However, WNT2 and PLCβ2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of the bone extracellular matrix. Furthermore, we found that the WNT/Ca2+ pathway may be responsible for regulating body growth. GHR was demonstrated by q-PCR and Western blot analyses to be expressed at low levels in long bones of Debao ponies. Treatment with WNT antagonistI decreased the expression of WNT pathway components (P GHR pathway components (P IGF-1 gene in the liver was lower in Debao ponies than in Mongolian horses at the juvenile and adult stages. Detection of plasma hormone concentrations showed that Debao ponies expressed higher levels of IGF-1 as juveniles and higher levels of GH as adults than Mongolian horses, indicating that the hormone regulation in Debao ponies differs from that in Mongolian horses. Conclusion Our work provides insights into the genetic regulation of short stature growth in mammals and can provide useful information for the development of therapeutic strategies for small size.

Bursaphelenchus xylophilus (B. xylophilus) is a dangerous plant pest which could result in Pine Wild Disease (PWD). To investigate the physiological activity of B. xylophilus and utilize the fluorescent properties of quantum dots, carbon quantum dots (CQDs) using glucose as precursor were synthesized through a hydrothermal reaction. The properties of the CQDs strongly depended on the reaction temperature and reaction time. The transcriptome analysis was implemented to study the molecular toxicology mechanism of CQDs on B. xylophilus. Based on the analysis results, it can be concluded that CQDs have the potential to stimulate the detoxification process and fatty acid degradation mechanism of B. xylophilus. Through observing the biodistribution of CQDs, lifespan, locomotion and egg-laying behavior of B. xylophilus, the intestine was the main target organ of the CQDs, and the CQDs could affect the locomotion and reproduction activities of B. xylophilus.

Splicing factors (SFs) have been increasingly documented to perturb the genome of cancers. However, little is known about the alterations of SFs in hepatocellular carcinoma (HCC). This study comprehensively delineated the genomic and epigenomic characteristics of 404 SFs in HCC based on the multi-omics data from the Cancer Genome Atlas database. The analysis revealed several clinically relevant SFs that could be effective biomarkers for monitoring the onset and prognosis of HCC (such as, HSPB1, DDX39A, and NELFE, which were the three most significant clinically relevant SFs). Functional enrichment analysis of these indicators showed the enrichment of pathways related to splicing and mRNA processes. Furthermore, the study found that SF copy number variation is common in HCC and could be a typical characteristic of hepato-carcinogenesis; the complex expression regulation of SFs was significantly affected by copy number variant and methylation. Several SFs with significant mutation patterns were identified (such as, RNF213, SF3B1, SPEN, NOVA1, and EEF1A1), and the potential regulatory network of SFs was constructed to identify their potential mechanisms for regulating clinically relevant alternative splicing events. Therefore, this study established a foundation to uncover the broad molecular spectrum of SFs for future functional and therapeutic studies of HCC., Graphical abstract

Xanthomonas oryzae pathovars oryzae (Xoo) and oryzicola (Xoc) infect rice, causing bacterial blight and bacterial leaf streak, respectively, which are two economically important bacterial diseases in paddy fields. The interactions of Xoo and Xoc with rice can be used as models for studying fundamental aspects of bacterial pathogenesis and host tissue specificity. However, an improved vector system for gene expression analysis is desired for Xoo and Xoc because some broad host range vectors that can replicate stably in X. oryzae pathovars are low‐copy number plasmids. To overcome this limitation, we developed a modular plasmid assembly system to transfer the functional DNA modules from the entry vectors into the pHM1‐derived backbone vectors on a high‐copy number basis. We demonstrated the feasibility of our vector system for protein detection, and quantification of virulence gene expression under laboratory conditions and in association with host rice and nonhost tobacco cells. This system also allows execution of a mutant complementation equivalent to the single‐copy chromosomal integration system and tracing of pathogens in rice leaf. Based on this assembly system, we constructed a series of protein expression and promoter‐probe vectors suitable for classical double restriction enzyme cloning. These vector systems enable cloning of all genes or promoters of interest from Xoo and Xoc strains. Our modular assembly system represents a versatile and highly efficient toolkit for gene expression analysis that will accelerate studies on interactions of X. oryzae with rice., We developed a modular plasmid assembly system to transfer DNA modules from entry vectors into high‐copy number pHM1‐derived vectors and use it for protein detection, mutant complementation, and tracing pathogens in leaves.

Arsenic is an established human carcinogen that can induce DNA damage; however, the precise mechanism remains unknown. Histone modification is of great significance in chemical toxicity and carcinogenesis. To investigate the role of histone H3K9me2 in arsenic-induced DNA damage, HaCaT cells were exposed to sodium arsenite in this study, and the results showed that the enrichment level of H3K9me2 at the N-methylated purine-DNA-glycosylase (MPG), X-ray repair cross-complementary gene 1 (XRCC1), and polyadenylate diphosphate ribose polymerase-1 (PARP1) promoter regions of base-excision repair (BER) genes was increased, which inhibited the expression of these BER genes, thereby inhibiting the repair of DNA damage and aggravating the DNA damage. Furthermore, the molecular mechanism by which H3K9me2 participates in the BER repair of arsenic-induced DNA damage was verified based on functional loss and gain experiments. In addition, Ginkgo biloba extract can upregulate the expression of MPG, XRCC1, and PARP1 and ameliorate cell DNA damage by reducing the enrichment of H3K9me2 at repair gene promoter regions.

Background. COVID-19 caused by SARS-CoV-2 infection has been spreading through many countries since the end of 2019. The 4th edition of the national guidelines for the management of COVID-19 provides an herbal formula with 9 herbs for its management. Aim of Study. We aimed to predict the mechanism of binding of SARS-CoV-2 and SARS-CoV spike glycoproteins with angiotensin-converting enzyme 2 (ACE2) to provide a molecular-level explanation of the higher pathogenicity of SARS-CoV-2 and to identify protein sites which may be targeted by therapeutic agents to disrupt virus-host interactions. Subsequently, we aimed to investigate the formula for the initial-stage management to identify a therapeutic agent with the most likely potential to become pharmaceutical candidate for the management of this disease. Materials and Methods. GenBank and SWISS-MODEL were applied for model creation. ClusPro was used for protein-protein docking. PDBePISA was applied for identification of possible binding sites. TCMSP was employed for identification of the chemical compounds. AutoDock Vina together with PyRx was used for the prediction and evaluation of binding pose and affinity to ACE2. SwissADME and PreADME were applied to screening and prediction of the pharmacokinetic properties of the identified chemical compounds. PyMOL was used to visualise the structural models of SARS-CoV-2 and SARS-CoV spike glycoproteins complexed to ACE2 and to examine their interactions. Results. SARS-CoV-2 had two chains (labelled chains B and C) which were predicted to bind with ACE2. In comparison, the SARS-CoV had only one chain (labelled chain C) predicted to bind with ACE2. The spike glycoproteins of both viruses were predicted to bind with ACE2 via position 487. Molecular docking screening and pharmacokinetic property prediction of the herbal compounds indicated that atractylenolide III (−9.1 kcal/mol) from Atractylodes lancea (Thunb.) Dc. (Cangzhu) may be a candidate therapeutic agent for initial-stage management. Conclusions. Atractylenolide III is predicted to have a strong binding affinity with ACE2 and eligible pharmacokinetic properties, anti-inflammatory effects and antiviral effects in in vitro study, and high distribution on the lungs in in vivo study.

Phytochemical investigation on the ethanol extract of green walnut husks (Juglans mandshurica Maxim.) led to the isolation of two previously unknown compounds, including a macrolide compound (13S)-8-oxo-(9E, 11E)-8-oxo-octadeca-9,11-dien-13-olide (1) and a diarylheptanoid compound 1-(3'-methoxy-4'-hydroxyphenyl)-7-(3″,4″-dimethoxyphenyl)heptan-3-one (2), together with 19 known compounds. The structures of these 21 compounds were elucidated by extensive analyses of NMR and HR-MS data, and the basis of spectroscopic analysis.

To achieve stable partial nitrification, activated sludge from a wastewater treatment plant using free ammonia (FA) inhibition was immobilized in a polyvinyl alcohol carrier. After FA treatment at 16.44 mg L−1 for 1 day, due to the increased growth rate gap between ammonium-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB), AOB enrichment and NOB inhibition were achieved within 12 days, with AOB and NOB accounting for 65.61 and 0.05%, respectively. Subsequently, with dissolved oxygen concentrations of 4−5 mg L−1, pH of 7.6–7.8 and temperature of 25 ± 1 °C, the immobilized carrier made of activated sludge achieved more than 90% and more than 86% of nitrite accumulation rate at the influent ammonia concentration of 90−110 mg L−1 and 35−50 mg L−1, respectively. After 50 days operation, the NOB content was 0.10%, indicating the immobilized carrier provided favorable conditions for maintaining the low NOB content. Furthermore, due to the low NOB content in the inoculum and the oxygen-limited environment formed by the increase in the AOB numbers in the carrier, immobilized carrier with different initial biomass (1, 2.5 and 5%) can achieve stable partial nitrification.

Background Sonic Hedgehog (SHh) signaling pathway plays a critical role in cell proliferation, apoptosis, and tumor angiogenesis in various types of malignancies including colorectal cancer (CRC). Qingjie Fuzheng Granules (QFG) is a traditional Chinese medicinal formula, which has been clinically used in various cancer treatments, including CRC. In this study, we explored the potential molecular mechanisms of QFG treatment effects on CRC via the SHh pathway. Methods A CRC HCT-116 xenograft mouse model was utilized for all experiments. Mice were treated with intra-gastric administration of 1 g/kg of QFG or saline 6 days a week for 28 days (4 weeks). Body weight, length and shortest diameter of the tumor were measured every 3 days. At the end of the treatment, the tumor weight was measured. TUNEL staining assays were used to detect tumor apoptosis. Western blot and immunohistochemistry (IHC) assays were used to detect the expression of relative proteins. Results In our results, QFG inhibited the increase of tumor volume and weight, and exhibited no impact on mouse body weight. Furthermore, QFG significantly decreased the expression of SHh, Smo and Gli proteins, indicating the action of SHh signaling. Consequently, the expression of pro-proliferative survivin, Ki-67, Cyclin-D1 and CDK4 were decreased and expression of anti-proliferative p21 was increased. The pro-apoptotic Bax/Bcl-2 ratio, cle-caspase-3 and TUNEL-positive cell percentage in tumor tissues were increased. Meanwhile, the pro-angiogenic VEGF-A and VEGFR-2 expression was down-regulated. Conclusions QFG inhibited CRC cell proliferation and promoted CRC cell apoptosis and tumor angiogenesis in vivo through the suppression of SHh pathway, suggesting that QFG could be a potential therapeutic drug for CRC.

Our aim was to verify whether genes in the coagulation complement and cytokine interaction pathways are crucial to the resistance to grass carp hemorrhagic disease in grass carps (Ctenopharyngodon idella). To evaluate this, we acquired male grass carps with grass carp reovirus (GCRV) resistance, F1 generation, ordinary male fish, control F1 progenies (hybridized ordinary fish), and barbel chub (Squaliobarbus curriculus) as a positive control. We compared the expression variation of 13 immune factors in different tissues using real-time fluorescent quantitative PCR. Our results showed that the expression of the transforming growth factor-β3, nerve growth factor receptor, coagulation factor D, chemokine receptor XCR1, profibrinolysin, γ-globulin of complement component 1, complement component 2, and complement component 5 in the different tissues of the barbel chub were significantly higher than those in the grass carps populations under normal conditions. Except for a limited number of genes, their expression exhibited significant differences. There was no significant difference in these genes among grass carp populations with different GCRV resistance. These results indicate that the high gene expression in the coagulation complement and cytokine interaction pathways may be the main reason for the strong resistance of barbel chub to GCRV. However, high gene expression was not a factor affecting GCRV resistance between grass carp populations.

Accumulating evidence suggests that chronic metformin posttreatment offers potent neuroreparative effects against acute brain injury. However, in previous studies, metformin was not initially administered beyond 24 h postinjury, and the effects of delayed metformin treatment in traumatic brain injury (TBI) and other types of acute brain injury and the related mechanisms are unclear. To test this, male C57BL/6 mice received once daily metformin treatment (20, 50 or 100 mg/kg/d, i.p.) at day 1–14, day 1–2, day 1–10, day 3–10, day 5–12 or day 5–28 after cryogenic TBI (cTBI). The results showed that 100 mg/kg/d metformin administered at day 1–14 postinjury significantly promoted motor functional recovery in the beam walking and gait tests and reduced the infarct volume. Metformin (100 mg/kg/d) administered at day 1–10 or day 3–10 but not day 1–2 or day 5–12 after cTBI significantly improved motor functional outcomes at day 7 and 14, and reduced the infarct volume at day 14. Interestingly, the therapeutic time window was further expanded when the duration of metformin treatment starting at day 5 postinjury was extended to 2 weeks. Furthermore, compared with cTBI, the administration of metformin at day 3–10 or day 5–28 after cTBI significantly elevated the expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and growth associated protein 43 (an axonal regeneration marker) and the number of vascular branch points and decreased the area of glial scar and the number of amoeboid microglia in the peri-infarct area at day 14 or 28 postinjury. The above beneficial effects of metformin were blocked by the intracerebroventricular injection of the AMPK inhibitor compound C (40 μg/mouse/d). Our data provide the first evidence that metformin has a wide therapeutic time window for at least 5 days after cTBI, during which it can improve functional recovery by promoting tissue repair and inhibiting glial scar formation and microglial activation in a central AMPK-dependent manner.

Three placodioid lichen species, Lecanora valesiaca, Protoparmeliopsis sierrae, and Rhizoplaca phaedrophthalma, are reported for the first time from China. Detailed taxonomic descriptions with high resolution photographs, chemistry, remarks, and distribution are provided.

BACKGROUNDInfertility is a major issue in human reproductive health, affecting an estimated 15% of couples worldwide. Infertility can result from disorders of sex development (DSD) or from reproductive endocrine disorders (REDs) with onset in infancy, early childhood or adolescence. Male infertility, accounting for roughly half of all infertility cases, generally manifests as decreased sperm count (azoospermia or oligozoospermia), attenuated sperm motility (asthenozoospermia) or a higher proportion of morphologically abnormal sperm (teratozoospermia). Female infertility can be divided into several classical types, including, but not limited to, oocyte maturation arrest, premature ovarian insufficiency (POI), fertilization failure and early embryonic arrest. An estimated one half of infertility cases have a genetic component; however, most genetic causes of human infertility are currently uncharacterized. The advent of high-throughput sequencing technologies has greatly facilitated the identification of infertility-associated gene mutations in patients over the past 20 years.OBJECTIVE AND RATIONALEThis review aims to conduct a narrative review of the genetic causes of human infertility. Loss-of-function mutation discoveries related to human infertility are summarized and further illustrated in tables. Corresponding knockout/mutated animal models of causative genes for infertility are also introduced.SEARCH METHODSA search of the PubMed database was performed to identify relevant studies published in English. The term ‘mutation’ was combined with a range of search terms related to the core focus of the review: infertility, DSD, REDs, azoospermia or oligozoospermia, asthenozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF), primary ciliary dyskinesia (PCD), acephalic spermatozoa syndrome (ASS), globozoospermia, teratozoospermia, acrosome, oocyte maturation arrest, POI, zona pellucida, fertilization defects and early embryonic arrest.OUTCOMESOur search generated ∼2000 records. Overall, 350 articles were included in the final review. For genetic investigation of human infertility, the traditional candidate gene approach is proceeding slowly, whereas high-throughput sequencing technologies in larger cohorts of individuals is identifying an increasing number of causative genes linked to human infertility. This review provides a wide panel of gene mutations in several typical forms of human infertility, including DSD, REDs, male infertility (oligozoospermia, MMAF, PCD, ASS and globozoospermia) and female infertility (oocyte maturation arrest, POI, fertilization failure and early embryonic arrest). The causative genes, their identified mutations, mutation rate, studied population and their corresponding knockout/mutated mice of non-obstructive azoospermia, MMAF, ASS, globozoospermia, oocyte maturation arrest, POI, fertilization failure and early embryonic arrest are further illustrated by tables. In this review, we suggest that (i) our current knowledge of infertility is largely obtained from knockout mouse models; (ii) larger cohorts of clinical cases with distinct clinical characteristics need to be recruited in future studies; (iii) the whole picture of genetic causes of human infertility relies on both the identification of more mutations for distinct types of infertility and the integration of known mutation information; (iv) knockout/mutated animal models are needed to show whether the phenotypes of genetically altered animals are consistent with findings in human infertile patients carrying a deleterious mutation of the homologous gene; and (v) the molecular mechanisms underlying human infertility caused by pathogenic mutations are largely unclear in most current studies.WILDER IMPLICATIONSIt is important to use our current understanding to identify avenues and priorities for future research in the field of genetic causes of infertility as well as to apply mutation knowledge to risk prediction, genetic diagnosis and potential treatment for human infertility.

To explore whether epigallocatechin-3-gallate (EGCG) improves renal damage in diabetic db/db mice and high-glucose- (HG-) induced injury in HK-2 cells by regulating the level of Klotho gene promoter methylation. Western blotting was used to detect the protein expression levels of DNA methyltransferase 1 (DNMT1), DNMT3a, DNMT3b, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), and Klotho. The methylation level of the Klotho gene promoter was detected by pyrosequencing. Chromatin immunoprecipitation was used to detect the binding of the Klotho gene promoter to DNMT1 and DNMT3a. The expression of oxidative stress markers (reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and 8-hydroxy-2′-deoxyguanosine (8-OHdG)) and inflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) in kidney homogenates was also measured using ELISA. Klotho and DNMT3b protein expression was upregulated, while DNMT1, DNMT3a, TGF-β1, and α-SMA protein expression was downregulated after EGCG treatment. EGCG treatment also reduced the methylation level of the Klotho gene promoter as well as the binding of DNMT3a to the Klotho gene promoter. In addition, EGCG treatment significantly decreased the levels of ROS, MDA, 8-OHdG, IL-1β, IL-6, and TNF-α and increased the levels of CAT and SOD. Under HG conditions, EGCG regulated Klotho gene promoter methylation via DNMT3a and decreased the methylation level of the Klotho gene promoter, thereby upregulating the expression of the Klotho protein to exert its protective effect.

Pyrrosia petiolosa, Pyrrosia lingua and Pyrrosia sheareri are recorded as original plants of Pyrrosiae Folium (PF) and commonly used as Chinese herbal medicines. Due to the similar morphological features of PF and its adulterants, common DNA barcodes cannot accurately distinguish PF species. Knowledge of the chloroplast (cp) genome is widely used in species identification, molecular marker and phylogenetic analyses. Herein, we determined the complete cp genomes of three original species of PF via high-throughput sequencing technologies. The three cp genomes exhibited a typical quadripartite structure with sizes ranging from 158 165 to 163 026 bp. The cp genomes of P. petiolosa and P. lingua encoded 130 genes, whilst that of P. sheareri encoded 131 genes. The complete cp genomes were compared, and five highly divergent regions of petA-psbJ, matK-rps16, ndhC-trnM, psbM-petN and psaC-ndhE were screened as potential DNA barcodes for identification of Pyrrosia genus species. The phylogenetic tree we obtained indicated that P. petiolosa and P. lingua are clustered in a single clade and, thus, share a close relationship. This study provides invaluable information for further studies on the species identification, taxonomy and phylogeny of Pyrrosia genus species.

Chitinase degrades chitin in the old epidermis or peritrophic matrix of insects, which ensures normal development and metamorphosis. In our previous work, we comprehensively studied the function of SfCht7 in Sogatella furcifera. However, the number and function of chitinase genes in S. furcifera remain unknown. Here, we identified 12 full-length chitinase transcripts from S. furcifera, which included nine chitinase (Cht), two imaginal disc growth factor (IDGF), and one endo-β-N-acetylglucosaminidase (ENGase) genes. Expression analysis results revealed that the expression levels of eight genes (SfCht3, SfCht5, SfCht6-1, SfCht6-2, SfCht7, SfCht8, SfCht10, and SfIDGF2) with similar transcript levels peaked prior to molting of each nymph and were highly expressed in the integument. Based on RNA interference (RNAi), description of the functions of each chitinase gene indicated that the silencing of SfCht5, SfCht10, and SfIDGF2 led to molting defects and lethality. RNAi inhibited the expressions of SfCht5, SfCht7, SfCht10, and SfIDGF2, which led to downregulated expressions of chitin synthase 1 (SfCHS1, SfCHS1a, and SfCHS1b) and four chitin deacetylase genes (SfCDA1, SfCDA2, SfCDA3, and SfCDA4), and caused a change in the expression level of two trehalase genes (TRE1 and TRE2). Furthermore, silencing of SfCht7 induced a significant decrease in the expression levels of three wing development-related genes (SfWG, SfDpp, and SfHh). In conclusion, SfCht5, SfCht7, SfCht10, and SfIDGF2 play vital roles in nymph-adult transition and are involved in the regulation of chitin metabolism, and SfCht7 is also involved in wing development; therefore, these genes are potential targets for control of S. furcifera.

Thyroid cancer (TC) is a frequently occurring malignant tumor with a rising steadily incidence. microRNA (miRNA/miR)-193a-3p is an miRNA that is associated with tumors, playing a crucial role in the genesis and progression of various cancers. However, the expression levels of miR-193a-3p and its molecular mechanisms in TC remain to be elucidated. The present study aimed to probe the expression of miR-193a-3p and its clinical significance in TC, including its underlying molecular mechanisms. Microarray and RNA sequencing data gathered from three major databases, specifically Gene Expression Omnibus (GEO), ArrayExpress and The Cancer Genome Atlas (TCGA) databases, and the relevant data from the literature were used to examine miR-193a-3p expression. Meta-analysis was also conducted to evaluate the association between clinicopathological parameters and miR-193a-3p in 510 TC and 59 normal samples from the TCGA database. miRWalk 3.0, and the TCGA and GEO databases were used to predict the candidate target genes of miR-193a-3p. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network enrichment analyses were conducted by using the predicted candidate target genes to investigate the underlying carcinogenic mechanisms. A dual luciferase assay was performed to validate the targeting regulatory association between the most important hub gene cyclin D1 (CCND1) and miR-193a-3p. miR-193a-3p expression was considerably downregulated in TC compared with in the non-cancer controls (P

Background: Although the efficacy of ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) for primary biliary cholangitis (PBC) has been suggested by small trials, a meta-analysis to summarize the evidence has not yet been carried out. The aim of this study was to evaluate the clinical outcomes of the combination therapy of UDCA and OCA compared with UDCA monotherapy in patients with PBC. Methods and materials: We searched the PubMed, EMBASE, the web of science, and the Cochrane Library databases for English-language studies published before September 2018. Studies were included if they were randomized controlled trials (RCTs) and reported relative risk (RR) estimates with 95% confidence intervals (CIs) or related data for the clinical outcomes of different therapies in patients with PBC. Results: Of the 1169 titles identified, two studies meeting the inclusion criteria were included in the meta-analysis. Approximately 222 patients with PBC were included in this analysis. The results of this study indicated that combination therapy was significantly superior to monotherapy in reducing serum alanine transaminase (mean difference: –15.63 IU/L; 95% CI, –21.59 to –9.68), aspartate transaminase (mean difference: –6.63 IU/L; 95% CI, –11.03 to –2.24), gamma-glutamyl transpeptidase (mean difference: –131.30 IU/L; 95% CI, –177.52 to –85.08), and C-reactive protein (mean difference = –1.17 mg/L; 95% CI, –2.19 to –0.14), but NS in improving primary endpoints of alkaline phosphatase level with 15.0% reduction from baseline, and equal or higher than the upper limit of normal serum total bilirubin (RR = 2.75; 95% CI, 0.43–17.68), conjugated bilirubin (mean difference = –0.06 mg/dL; 95% CI, –0.28 to 0.15), IgM (mean difference = –41.18 mg/dL; 95% CI, –244.45 to 162.09), and adverse events (P > 0.05). Conclusion: This meta-analysis demonstrated that combination therapy with UDCA and OCA provided satisfactory clinical outcomes, which may be a promising alternative for patients with PBC who had an inadequate response to UDCA therapy. Therefore, high-quality RCTs on the safety and efficacy of the combination therapy of UDCA and OCA compared with UDCA monotherapy in patients with PBC should be performed in the future.

Long-term arsenic exposure is a worldwide public health problem that causes serious harm to human health. The liver is the main target organ of arsenic toxicity; arsenic induces disruption of the DNA damage repair pathway, but its mechanisms remain unclear. In recent years, studies have found that epigenetic mechanisms play an important role in arsenic-induced lesions. In this study, we conducted experiments in vitro using normal human liver cells (L-02) to explore the mechanism by which the histone demethylase JHDM2A regulates H3K9 dimethylation (me2) in response to arsenic-induced DNA damage. Our results indicated that arsenic exposure upregulated the expression of JHDM2A, downregulated global H3K9me2 modification levels, increased the H3K9me2 levels at the promoters of base excision repair (BER) genes (N-methylpurine-DNA glycosylase [MPG], XRCC1 and poly(ADP-ribose)polymerase 1) and inhibited their expression levels, causing DNA damage in cells. In addition, we studied the effects of overexpression and inhibition of JHDM2A and found that JHDM2A can participate in the molecular mechanism of arsenic-induced DNA damage via the BER pathway, which may not be involved in the BER process because H3K9me2 levels at the promoter region of the BER genes were unchanged following JHDM2A interference. These results suggest a potential mechanism by which JHDM2A can regulate the MPG and XRCC1 genes in the process of responding to DNA damage induced by arsenic exposure and can participate in the process of DNA damage repair, which provides a scientific basis for understanding the epigenetic mechanisms and treatments for endemic arsenic poisoning.

Increased atmospheric CO2 concentrations may directly affect insect behavior and physiology. Native and invasive insects may have different levels of adaptability to elevated CO2. The invasive species Frankliniella occidentalis and the native species Thrips hawaiiensis are economically important pests. We determined the effects of elevated CO2 on these pests by monitoring their development, survival, and oviposition under different CO2 concentrations (400, 600, and 800 μl L−1). We also determined detoxifying enzyme activities in larvae and adults. Frankliniella occidentalis and T. hawaiiensis showed faster development but lower survival rates as the CO2 concentration increased. Fecundity significantly increased in F. occidentalis but decreased in T. hawaiiensis with increasing CO2 concentrations. The net reproductive rate (R0) and intrinsic rate of increase (rm) were highest in F. occidentalis and lowest in T. hawaiiensis in the highest CO2 treatment. At each CO2 concentration, compared with T. hawaiiensis, F. occidentalis developed faster and had higher survival rate, fecundity, R0, and rm. The activities of detoxifying enzymes, except for acetylcholinesterase activity in second instars, increased in both species with increasing CO2 concentrations. Carboxylesterase and glutathione S-transferase activities were always higher in F. occidentalis than in T. hawaiiensis. At each CO2 concentration, carboxylesterase and acetylcholinesterase activities were higher in adults, but glutathione S-transferase activities were higher in larvae, indicative of different physiological responses between adults and larvae. In summary, elevated CO2 benefited the population development of F. occidentalis but negatively affected that of T. hawaiiensis. This may be related to the activities of detoxifying enzymes.

One new phenolic glycoside, methyl 3,4-dihydroxyphenylacetate-4-O-[2-O-β-D-apisoyl-6-O-(2-hydroxybenzoyl)]-β-D-glucopyranoside (1), together with 10 known compounds (2–11), were isolated from the r...

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

To evaluate a radiomic approach for the stratification of diffuse gliomas with distinct prognosis and provide additional resolution of their clinicopathological and molecular characteristics. For this retrospective study, a total of 704 radiomic features were extracted from the multi-channel MRI data of 166 diffuse gliomas. Survival-associated radiomic features were identified and submitted to distinguish glioma subtypes using consensus clustering. Multi-layered molecular data were used to observe the different clinical and molecular characteristics between radiomic subtypes. The relative profiles of an array of immune cell infiltrations were measured gene set variation analysis approach to explore differences in tumor immune microenvironment. A total of 6 categories, including 318 radiomic features were significantly correlated with the overall survival of glioma patients. Two subgroups with distinct prognosis were separated by consensus clustering of radiomic features that significantly associated with survival. Histological stage and molecular factors, including IDH status and MGMT promoter methylation status were significant differences between the two subtypes. Furthermore, gene functional enrichment analysis and immune infiltration pattern analysis also hinted that the inferior prognosis subtype may more response to immunotherapy. A radiomic model derived from multi-parameter MRI of the gliomas was successful in the risk stratification of diffuse glioma patients. These data suggested that radiomics provided an alternative approach for survival estimation and may improve clinical decision-making.

Phytophthora nicotianae is a widespread cause of black shank disease of tobacco plants and causes substantial harvest losses in all major cultivation areas. The oomycete primarily affects plant roots and the stem, where it leads to a progressing decay of the diseased tissues. In this resource announcement, we provide two complementary datasets comprising 16S gene fragment amplicons (bacteriome) and ITS1 region amplicons (mycobiome) that were sequenced on an Illumina-based platform. Soil samples were obtained from disease-affected fields in Guizhou province (China) and include control samples from adhering fields without previous disease incidence. Both datasets were acquired at a high sequencing depth and accompanied by detailed metadata, which facilitate their implementation in comparative studies. The resource announcement provides a basis for disease-specific biomarker detection and correlation studies that include the microbiome.

Microalgae is a potential producer of functional lipids such as n-3 polyunsaturated fatty acids (PUFA) and fucoxanthin. In the present study, lipids from ten microalgae species were analyzed especially focusing on the fucoxanthin, lipid and fatty acid compositions. The study revealed a remarkable variation in total lipids content, fucoxanthin content, lipid class composition and n-3 PUFA content in individual species, although they belong to the same genus. Among microalgae examined, Pavlova lutheri contained the highest total lipids content (313.59 mg g-1 dry weight) and considerable amount of fucoxanthin (3.13 mg g-1 dry weight). It also had the highest level (28.01%) of total n-3 PUFA with high level of eicosapentaenoic acid (EPA) (17.76%) and docosahexaenoic acid (DHA) (7.61%). The highest fucoxanthin content (5.19 mg g-1 dry weight) was observed in Chaetoceros gracilis. C. gracilis also contained relatively high level of total lipids (228.87 mg g-1 dry weight) and 10.67% EPA. The results also demonstrated that Nannochloropsis oculata contained the greatest amount of EPA (26.21%), while Isochrysis galbana had the highest level of DHA (8.76%). And both microalgae contained 1.71 and 4.44 mg g-1 dry weight fucoxanthin, respectively. Microalgal lipids containing abundant fucoxanthin and n-3 PUFA such as EPA and DHA in the present study will be used as nutraceutical lipids with great commercial potential.

To achieve the stable partial nitrification of municipal wastewater, activated sludge with high ammonia-oxidizing bacteria (AOB) content and low nitrite-oxidizing bacteria (NOB) content were immobilized in a polyvinyl alcohol filler. The effects of different levels of dissolved oxygen (DO) on the activity of AOB and NOB in the filler with temperature changes at the initial ammonia concentration of approximately 100 mg L−1 were investigated. At 25 °C, when the DO concentration was greater than 5 mg L−1, the O2-limiting condition inside the filler was destroyed as the demand for oxygen in AOB was certain, and resulted in enhanced NOB activity. At 15 °C, the DO concentration was not a key factor in determining the NOB activity due to the negative effect of temperature on NOB activity. The immobilized filler reactor of municipal wastewater achieved a nitrite accumulation rate (NAR) of >86.7 and >82% at 24–26 °C and 14–16 °C, respectively. Low temperatures did not deteriorate the stable partial nitrification performance. The total nitrogen (TN) removal efficiency of the immobilized filler reactor was 21.7–26.1% and 10.3–15.3% at 24–26 °C and 14–16 °C, respectively. The TN removal efficiency and NAR in municipal wastewater were higher as compared to simulated wastewater, indicating that the organic carbon in municipal wastewater enhanced nitrate reduction by denitrification. High-throughput sequencing analysis showed that denitrifying bacteria and nitrifying bacteria were identified as the predominant bacteria genera, while the dominant species of NOB was Nitrobacter. This study is a viable approach to promoting partial nitrification in municipal WWTPs.

Aim: To identify potential key candidate genes, whose expression and clinical significance was further assessed in colorectal cancer (CRC). Methods: Three original microarray datasets (GSE41328, GSE22598, and GSE23878) from NCBI-GEO were used to analyze differentially expressed genes (DEGs) in CRC. Online database analyses through Oncomine and GEIPA were performed to evaluate SLC4A4 expression and explore the prognostic merit of SLC4A4 expression, which was further confirmed by analyses from QPCR based cDNA array and IHC based tissue microarray (TMA). STRING website was used to explore the interaction between SLC4A4 with other DEGs based on the protein-protein interaction (PPI) networks. Results: Analysis of three original microarray datasets from GEO identified 82 shared, differentially expressed genes (28 upregulated and 54 down-regulated) in CRC tissues. Online analyses from Oncomine and GEIPA revealed lower SLC4A4 mRNA expression in CRC tissues compared to adjacent normal tissues, which were further confirmed by QPCR based cDNA array and IHC based TMA analyses on both mRNA and protein levels. Survival analyses through GEIPA and from TMA demonstrated that low SLC4A4 expression is correlated with worse overall survival among patients with CRC. Survival analysis from Kaplan-meier plotter demonstrated that low SLC4A4 expression is significantly associated with poor progression (including relapse-free survival, overall survival, distant metastasis-free survival, post-progression survival) of patients with breast cancer, lung cancer, gastric cancer, and ovarian cancer. PPI analysis found that SLC4A4 is highly correlated with various genes, including SLC9A3, SLC26A6, ENSG00000214921, SLC26A4, SLC9A3R1, and SLC9A1. Conclusion: The mRNA and protein levels of SLC4A4 were decreased in CRC tissues, and low expression of SLC4A4 significantly correlated with shorter survival of CRC patients and poorer progression of patients with breast cancer, lung cancer, gastric cancer and ovarian cancer, suggesting potential role of SLC4A4 on tumor suppression and prognostic prediction in multiple malignancies including CRC.