A Novel lncRNA lncRNA-4045 Promotes the Progression of Hepatocellular Carcinoma by Affecting the Expression of AKR1B10.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been shown to be related to the occurrence and development of a variety of cancers including hepatocellular carcinoma (HCC). However, a large number of potential HCC-related lncRNAs remain undiscovered and are yet to be fully understood. METHODS: Differentially expressed lncRNAs were first obtained from the tumor tissues and adjacent normal tissues of five HCC patients using high-throughput microarray chips. Then the expression levels of 10 differentially expressed lncRNAs were verified in 50 pairs of tissue samples from patients with HCC by quantitative real-time PCR (qRT-PCR). The oncogenic effects of lncRNA-4045 (ENST00000524045.6) in HCC cell lines were verified through a series of in vitro experiments including CCK-8 assay, plate clone formation assay, transwell assay, scratch assay, and flow cytometry. Subsequently, the potential target genes of lncRNA-4045 were predicted by bioinformatics analysis, fluorescence in situ hybridization assay, and RNA sequencing. The mechanism of lncRNA-4045 in HCC was explored by WB assay as well as rescue and enhancement experiments. RESULTS: The results from microarray chips showed 1,708 lncRNAs to have been significantly upregulated and 2725 lncRNAs to have been significantly downregulated in HCC tissues. Via validation in 50 HCC patients, a novel lncRNA lncRNA-4045 was found significantly upregulated in HCC tissues. Additionally, a series of in vitro experiments showed that lncRNA-4045 promoted the proliferation, invasion, and migration of HCC cell lines, and inhibited the apoptosis of HCC cell lines. The results of qRT-PCR in HCC tissues showed that the expression levels of AKR1B10 were significantly positively correlated with lncRNA-4045. LncRNA-4045 knockdown significantly down-regulated AKR1B10 protein expression, and overexpression of lncRNA-4045 led to significant up-regulation of AKR1B10 protein in HCC cell lines. Lastly, down-regulation of AKR1B10 could partially eliminate the enhancement of cell proliferation induced by lncRNA-4045 overexpression, while up-regulation of AKR1B10 was shown to enhance those effects. CONCLUSION: LncRNA-4045 may promote HCC via enhancement of the expression of AKR1B10 protein.

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

Study on the mechanism of salt relief and growth promotion of Enterobacter cloacae on cotton.

AIMS: In-depth studies on plant ion uptake and plant growth-promoting rhizobacteria (PGPR) at the molecular level will help to further reveal the effects of PGPR on plants and their interaction mechanisms under salt stress. METHODS: Cotton was inoculated with a PGPR-Enterobacter cloacae Rs-35, and the ion uptake capacity, membrane transporter protein activity, and expression of key genes were determined under salt stress. Changes in the endogenous hormone content of cotton were also determined. Further, the genome-wide metabolic pathway annotation of E. cloacae Rs-35 and its differential enrichment pathway analysis of multi-omics under salinity environments were performed. RESULTS: In a pot experiment of saline-alkali soil, E. cloacae Rs-35-treated cotton significantly increased its uptake of K+ and Ca2+ and decreased uptake of Na+, elevated the activity of the H+-ATPase, and increased the sensitivity of the Na+/H+ reverse transporter protein on the vesicle membrane. Meanwhile, inoculation with E. cloacae Rs-35 could promote cotton to maintain the indole-3-acetic acid (IAA) content under salt stress. Genome-wide annotation showed that E. cloacae Rs-35 was respectively annotated to 31, 38, and 130 related genes in osmotic stress, phytohormone and organic acid metabolism, and ion uptake metabolic pathway. Multi-omics differences analysis showed that E. cloacae Rs-35 were enriched to tryptophan metabolism, multiple amino acid biosynthesis, carbon and glucose synthesis, and oxidative phosphorylation metabolic pathways at the transcriptome, proteome, and metabolome. CONCLUSION: E. cloacae Rs-35 can promote cotton balance cell ion concentration, stabilize intracellular IAA changes, stimulate induction of systemic tolerance, and promote the growth of cotton plants under salt stress.

Graphdiyne and its Composites for Lithium-Ion and Hydrogen Storage.

Graphynes (GYs) are a novel type of carbon allotrope composed of sp and sp2 hybridized carbon atoms, boasting both a planar conjugated structure akin to graphene and a pore-like configuration in three-dimensional space. Graphdiyne (GDY), the first successfully synthesized member of GYs family, has gained much interest due to its fascinating electrochemical properties including a greater theoretical capacity, high charge mobility and advanced electronic transport properties, making it a promising material for energy storage applications for lithium-ion and hydrogen storage. Various methods, including heteroatom substitution, embedding, strain, and nanomorphology control, have been employed to further enhance the energy storage performance of GDY. Despite the potential of GDY in energy storage applications, there are still challenges to overcome in scaling up mass production. This review summarizes recent progress in the synthesis and application of GDY in lithium-ion and hydrogen storage, highlighting the obstacles faced in large-scale commercial application of GDY-based energy storage devices. Suggestions on possible solutions to overcome these hurdles have also been provided. Overall, the unique properties of GDY make it a promising material for energy storage applications in lithium-ion and hydrogen storage devices. The findings presented here will inspire further development of energy storage devices utilizing GDY.

ProBDNF Dependence of LTD and Fear Extinction Learning in the Amygdala of Adult Mice.

Neurotrophins are secreted proteins that control survival, differentiation, and synaptic plasticity. While mature neurotrophins regulate these functions via tyrosine kinase signaling (Trk), uncleaved pro-neurotrophins bind preferentially to the p75 neurotrophin receptor (p75NTR) and often exert opposite effects to those of mature neurotrophins. In the amygdala, brain-derived neurotrophic factor (BDNF) enables long-term potentiation as well as fear and fear extinction learning. In the present study, we focused on the impact of mature BDNF and proBDNF signaling on long-term depression (LTD) in the lateral amygdala (LA). Hence, we conducted extracellular field potential recordings in an in vitro slice preparation and recorded LTD in cortical and thalamic afferents to the LA. LTD was unchanged by acute block of BDNF/TrkB signaling. In contrast, LTD was inhibited by blocking p75NTR signaling, by disinhibition of the proteolytic cleavage of proBDNF into mature BDNF, and by preincubation with a function-blocking anti-proBDNF antibody. Since LTD-like processes in the amygdala are supposed to be related to fear extinction learning, we locally inhibited p75NTR signaling in the amygdala during or after fear extinction training, resulting in impaired fear extinction memory. Overall, these results suggest that in the amygdala proBDNF/p75NTR signaling plays a pivotal role in LTD and fear extinction learning.

The number of metabolic syndrome risk factors predicts alterations in gut microbiota in Chinese children from the Huantai study.

BACKGROUND: Evidence on the effect of gut microbiota on the number of metabolic syndrome (MetS) risk factors among children is scarce. We aimed to examine the alterations of gut microbiota with different numbers of MetS risk factors among children. METHODS: Data were collected from a nested case-control study at the baseline of the Huantai Childhood Cardiovascular Health Cohort Study in Zibo, China. We compared the differences in gut microbiota based on 16S rRNA gene sequencing among 72 children with different numbers of MetS risk factors matched by age and sex (i.e., none, one, and two-or-more MetS risk factors; 24 children for each group). RESULTS: The community richness (i.e., the total number of species in the community) and diversity (i.e., the richness and evenness of species in the community) of gut microbiota decreased with an increased number of MetS risk factors in children (P for trend < 0.05). Among genera with a relative abundance greater than 0.01%, the relative abundance of Lachnoclostridium (PFDR = 0.009) increased in the MetS risk groups, whereas Alistipes (PFDR < 0.001) and Lachnospiraceae_NK4A136_group (PFDR = 0.043) decreased in the MetS risk groups compared to the non-risk group. The genus Christensenellaceae_R-7_group excelled at distinguishing one and two-or-more risk groups from the non-risk group (area under the ROC curve [AUC]: 0.84 - 0.92), while the genera Family_XIII_AD3011_group (AUC: 0.73 - 0.91) and Lachnoclostridium (AUC: 0.77 - 0.80) performed moderate abilities in identifying none, one, and two-or-more MetS risk factors in children. CONCLUSIONS: Based on the nested case-control study and the 16S rRNA gene sequencing technology, we found that dysbiosis of gut microbiota, particularly for the genera Christensenellaceae_R-7_group, Family_XIII_AD3011_group, and Lachnoclostridium may contribute to the early detection and the accumulation of MetS risk factors in childhood.

Estimating future PM2.5-attributed acute myocardial infarction incident cases under climate mitigation and population change scenarios in Shandong Province, China.

BACKGROUND: The effects of fine particulate matter (PM2.5) on acute myocardial infarction (AMI) have been widely recognized. However, no studies have comprehensively evaluated future PM2.5-attributed AMI burdens under different climate mitigation and population change scenarios. We aimed to quantify the PM2.5-AMI association and estimate the future change in PM2.5-attributed AMI incident cases under six integrated scenarios in 2030 and 2060 in Shandong Province, China. METHODS: Daily AMI incident cases and air pollutant data were collected from 136 districts/counties in Shandong Province from 2017 - 2019. A two-stage analysis with a distributed lag nonlinear model was conducted to quantify the baseline PM2.5-AMI association. The future change in PM2.5-attributed AMI incident cases was estimated by combining the fitted PM2.5-AMI association with the projected daily PM2.5 concentrations under six integrated scenarios. We further analyzed the factors driving changes in PM2.5-related AMI incidence using a decomposition method. RESULTS: Each 10 µg/m3 increase in PM2.5 exposure at lag05 was related to an excess risk of 1.3 % (95 % confidence intervals: 0.9 %, 1.7 %) for AMI incidence from 2017 - 2019 in Shandong Province. The estimated total PM2.5-attributed AMI incident cases would increase by 10.9-125.9 % and 6.4-244.6 % under Scenarios 1 - 3 in 2030 and 2060, whereas they would decrease by 0.9-5.2 % and 33.0-46.2 % under Scenarios 5 - 6 in 2030 and 2060, respectively. Furthermore, the percentage increases in PM2.5-attributed female cases (2030: -0.3 % to 135.1 %; 2060: -33.2 % to 321.5 %) and aging cases (2030: 15.2-171.8 %; 2060: -21.5 % to 394.2 %) would wholly exceed those in male cases (2030: -1.8 % to 133.2 %; 2060: -41.1 % to 264.3 %) and non-aging cases (2030: -41.0 % to 45.7 %; 2060: -89.5 % to -17.0 %) under six scenarios in 2030 and 2060. Population aging is the main driver of increased PM2.5-related AMI incidence under Scenarios 1 - 3 in 2030 and 2060, while improved air quality can offset these negative effects of population aging under the implementation of the carbon neutrality and 1.5 °C targets. CONCLUSION: The combination of ambitious climate policies (i.e., 1.5 °C warming limits and carbon neutrality targets) with stringent clean air policies is necessary to reduce the health impacts of air pollution in Shandong Province, China, regardless of population aging.

Association between gut microbiota and obesity combined with high carotid intima-media thickness among Chinese children.

BACKGROUND AND OBJECTIVES: Obesity and related target organ damage such as high carotid intima-media thickness (cIMT) in children is associated with cardiovascular disease (CVD) later in life. However, the asso-ciation between gut microbiota and obesity combined with high cIMT among children remains unclear. Therefore, we compared differences in composition, community diversity, and richness of gut microbiota among normal children and obesity combined with or without high cIMT to identify differential microbiota biomarkers. METHODS AND STUDY DESIGN: A total of 24 children with obesity combined with high cIMT (OB+high-cIMT), 24 with obesity but normal cIMT (OB+non-high cIMT), and 24 with normal weight and normal cIMT aged 10-11 years matched by age and sex from the "Huantai Childhood Cardiovascular Health Cohort Study" were included. All included fecal samples were tested using 16S rRNA gene sequencing. RESULTS: The community richness and diversity of gut microbiota in OB+high-cIMT children were decreased compared with OB+non-high cIMT children and normal children. At the genus level, the relative abundances of Christensenellaceae_R-7_group, UBA1819, Family_XIII_AD3011_group, and unclassi-fied_o_Bacteroidales were associated with reduced odds of OB+high-cIMT among children. Receiver operating characteristic (ROC) analysis showed that combined Christensenellaceae_R-7_group, UBA1819, Fami-ly_XIII_AD3011_group, and unclassified_o_Bacteroidales performed a high ability in identifying OB+high-cIMT. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed that several pathways such as biosynthesis of amino acids and aminoacyl-tRNA pathways were lower in the OB+high-cIMT group compared with the normal group. CONCLUSIONS: We found that the alteration of gut microbiota was associated with OB+high-cIMT among children, which indicates that the gut microbiota may be a marker for obesity and related cardiovascular damage among children.

Liver-specific LINC01146, a promising prognostic indicator, inhibits the malignant phenotype of hepatocellular carcinoma cells both in vitro and in vivo.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in the development of hepatocellular carcinoma (HCC). We aimed to investigate the function of LINC01146 in HCC. METHODS: The expression of LINC01146 in HCC tissues was explored via The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and was verified using quantitative real-time polymerase chain reaction (qRT-PCR) in our HCC cohort. Kaplan-Meier analysis was used to assess the relationship between LINC01146 and the prognosis of HCC patients. Cell Counting Kit 8, colony formation assays, Transwell assays, flow cytometric assays, and tumour formation models in nude mice were conducted to reveal the effects of LINC01146 on HCC cells both in vitro and in vivo. Bioinformatic methods were used to explore the possible potential pathways of LINC01146 in HCC. RESULTS: LINC01146 was significantly decreased in HCC tissues compared with adjacent normal tissues and was found to be related to the clinical presentations of malignancy and the poor prognosis of HCC patients. Overexpression of LINC01146 inhibited the proliferation, migration, and invasion of HCC cells in vitro, while promoting their apoptosis. In contrast, downregulation of LINC01146 exerted the opposite effects on HCC cells in vitro. In addition, overexpression of LINC01146 significantly inhibited tumour growth, while downregulation of LINC01146 promoted tumour growth in vivo. Furthermore, the coexpressed genes of LINC01146 were mainly involved in the "metabolic pathway" and "complement and coagulation cascade pathway". CONCLUSION: LINC01146 expression was found to be decreased in HCC tissues and associated with the prognosis of HCC patients. It may serve as a cancer suppressor and prognostic biomarker in HCC.

Liver-specific lncRNA FAM99A may be a tumor suppressor and promising prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: Increasing evidence shows that liver-specific long non-coding RNAs (lncRNAs) play important roles in the development of hepatocellular carcinoma (HCC). We identified a novel liver-specific lncRNA, FAM99A, and examined its clinical significance and biological functions in HCC. METHODS: The expression level and clinical value of FAM99A in HCC were examined using The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases, and were further verified using quantitative real-time polymerase chain reaction (qRT-PCR) in our HCC cohort. Univariate and multivariate Cox proportional hazards regression models were also applied to identify independent prognostic indicators for HCC patients. Cell counting kit-8, colony formation, and Transwell assays were performed to evaluate the effects of FAM99A on the proliferation, migration, and invasion abilities of HCC cells in vitro. A subcutaneous xenograft tumor model was implemented to determine the effect of FAM99A on the tumor growth of HCC cells in vivo. RNA pull-down and mass spectrometry assays were performed to reveal the potential molecular mechanisms of FAM99A in HCC. RESULTS: The three public online databases and qRT-PCR data showed that FAM99A was frequently downregulated in HCC tissues and inversely correlated with microvascular invasion and advanced histological grade of HCC patients. Kaplan-Meier survival analysis indicated that decreased FAM99A was significantly associated with poor overall survival of HCC patients based on TCGA database (P = 0.040), ICGC data portal (P < 0.001), and our HCC cohort (P = 0.010). A multivariate Cox proportional hazards regression model based on our HCC cohort suggested that FAM99A was an independent prognostic factor of overall survival for HCC patients (hazard ratio: 0.425, P = 0.039). Upregulation of FAM99A suppressed the proliferation, colony formation, migration, and invasion capacities of HCC cells in vitro, and knockdown of FAM99A had the opposite effects. A subcutaneous xenograft tumor model demonstrated that overexpression of FAM99A significantly inhibited the tumor growth of HCC cells in vivo. Seven tumor-related proteins (PCBP1, SRSF5, SRSF6, YBX1, IGF2BP2, HNRNPK, and HNRNPL) were recognized as possible FAM99A-binding proteins by the RNA pull-down and mass spectrometry assays. CONCLUSION: Our results suggest that FAM99A exerts cancer-inhibiting effects on HCC progression, and it may be a promising prognostic indicator for HCC patients.

The risk factors and nursing countermeasures of sepsis after cesarean section: a retrospective analysis.

BACKGROUND: Sepsis is a very serious complication of cesarean section, understanding the influencing factors is important to the prevention and management of sepsis. We aimed to analyze the associated risk factors of sepsis of cesarean section, to provide evidences into the clinical management and nursing care of cesarean section. METHODS: Patients who underwent cesarean section surgery from January 1, 2017 to June 30, 2021 in our hospital were included. The characteristics of patients were collected and analyzed. Logistic regression analyses were conducted to analyze the influencing factors of sepsis of cesarean section. RESULTS: A total of 3819 patients undergoing cesarean section were included, the incidence of sepsis in patients undergoing cesarean section was 0.84%. There were significant differences in the age, vaginal delivery attempt, premature rupture of membranes, preoperative hemoglobin, estimated blood loss during surgery and postoperative urinary tube implacement between sepsis and no sepsis patients (all p < 0.05). Logistic regression analyses found that age ≥ 35y(OR3.22, 95%CI1.20 ~ 5.15), gestational diabetes(OR2.64, 95%CI1.91 ~ 4.15), vaginal delivery attempt(OR2.05, 95%CI1.70 ~ 4.42), premature rupture of membranes(OR2.42, 95%CI1.02 ~ 4.20), preoperative hemoglobin ≤ 105 g/L(OR4.39, 95%CI1.02 ~ 7.88), estimated blood loss during surgery ≥ 400 ml(OR1.81, 95%CI1.35 ~ 3.01), postoperative urinary tube implacement(OR2.19, 95%CI1.27 ~ 2.50) were the risk factors of sepsis in patients undergoing cesarean section(all p < 0.05). Escherichia Coli(46.15%), Enterococcus faecalis(17.95%) and Pseudomonas aeruginosa(12.83%) were the most commonly-seen bacteria in sepsis patients. CONCLUSION: In clinical practice, medical workers should carry out strict management and early prevention of related risk factors during the perioperative period of pregnant women, to effectively reduce the occurrence of sepsis after cesarean section.

Evaluation of Corneal and Retinal Toxicity in Rheumatoid Arthritis Patients Treated with Hydroxychloroquine.

INTRODUCTION: The study aimed to assess the ocular toxicity of hydroxychloroquine (HCQ) by confocal microscopy, multifocal electroretinography (mfERG), and scanning laser polarimetry with variable corneal compensation (GDxVCC) in patients with rheumatoid arthritis (RA). METHODS: A cross-sectional, comparative case series study was retrospectively conducted on 61 patients under HCQ treatment for RA without fundoscopic anomalies (group 1), 65 RA patients with no HCQ treatment (group 2), and 27 normal subjects (group 3). A comprehensive ophthalmological examination, including confocal microscopy, mfERG, and GDxVCC, was performed in the three groups. RESULTS: In group 1, the duration of treatment ranged from 19 to 96 months (54.9 ± 15.2 months). The mean cumulative dose of HCQ was 446.1 ± 164.0 g (range 114-864 g). Confocal microscopy revealed hyper-reflective abnormal particles in 45 patients (73.8%) and beaded, tortuous fibers in 34 patients (55.7%) in group 1. No corneal change was observed in the other two groups. The mfERG responses in the 6 concentric rings (R1-R6) among the three groups differed except at R3 (all p < 0.05), and data from R1-R6 were not significantly different between groups 2 and 3. The retinal nerve fiber layer thicknesses were statistically thinner in group 1 than in groups 2 and 3 (all p < 0.05). CONCLUSIONS: Early signs of corneal and neural retina structure changes were detected in patients with RA treated with HCQ. Whether these findings should be a mark of drug recession still needs further study and more evidence.

MiRNA-21-HIF-1α-VEGF Axis Is Associated with Myopic Choroidal Neovascularization in Guinea Pigs.

INTRODUCTION: Myopic choroidal neovascularization (CNV) often causes serious damage to central vision. The mechanisms behind it remain unclear. METHOD: In this study, monocular form deprivation was applied to induce high myopia, and 532-nm laser was employed to induce CNV in guinea pig. The development of neovascularization was measured comprehensively by fundus fluorescein angiography, optical coherence tomography and hematoxylin and eosin staining. Gene expression was detected by real-time polymerase chain reaction and immunohistochemistry. RESULTS: The proliferation of new blood vessels increased with time and peaked at 21 days. At each time point after laser photocoagulation, the incidence of CNV was higher in form-deprived myopia (FDM) group than in control group. Myopic CNV started earlier and decreased more slowly. The obvious continuous fluorescein leakage could last as long as 1 month. The expressions of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) increased and peaked at 14 days in both groups after laser photocoagulation. Moreover, after laser photocoagulation, miR-21 expression was upregulated in both groups, reached a peak at 7 days, with a level much higher in FDM group. In addition, miR-21 expression was positively correlated with VEGF and HIF-1α expression in both groups. CONCLUSION: miR-21 correlated with HIF-1α-VEGF signaling pathway may promote CNV formation in high-myopia guinea.

First report of leaf blight caused by Pantoea agglomerans on wheat in China.

Wheat (Triticum aestivum L.) is the main grain crop in Ningxia Hui Autonomous Region, China. A new leaf blight disease of wheat was observed in many wheat fields in Yinchuan City and Wuzhong City of Ningxia during 2020-2021. The average disease incidence of the cultivar Ningchun 50 was 5 to 15%, and there appeared the evident disease symptoms from the heading stage, then the symptoms got more serious until the mature stage. The tips of the leaves were chlorotic and turned bright yellow at the early stage of the disease. Later on, the yellow leaf spots were further spread from the tip to the petiole, and the yellow-colored necrotic lesions emerged, resulted in withering and death of leaves (e-Xtra 1, a-d). To isolate and identify the pathogenic agent, diseased leaves were cut into 0.5 cm × 0.5 cm small pieces, and sterilized in 5% NaOCl solution for 5 min, and were rinsed three times in sterile water, then crushed with tweezers in 2 mL sterilized water and streaked three times onto Nutrient Agar (NA) medium. and 15 single colonies which had the same colony morphology were obtained. Of the 15 colonies, 3 (named WH1, Cx1 and HJ1) were randomly selected for further morphological, biochemical and molecular characterization. The resulting bacterial colonies were incubated at 29±1°C in the dark for 3 days, colony morphology was raised, mucoid texture, round, and smooth with entire margin; the color of these colonies was white at the beginning and turned yellow later. These bacteria were rod-shaped gram-negative cells with peritrichous flagella. Based on the physiological and biochemical assay results (e-Xtra 2), the three strains were initially identified as Pantoea agglomerans (Wang, D H., et al. 2021; Wang, J J., et al. 2021). 16S rDNA and gyrB of the three strains were amplified and sequenced by ABI3730XL sequencer in GENEWIZ (Suzhou, China). The sequences of 16S rDNA and gyrB of these strains were submitted to GenBank with the accession numbers ON428446, ON428461 and ON428462 for 16S rDNA; ON461799, ON461801, ON461803 for gyrB. 16S rDNA and gyrB sequences homology analysis showed that the three strains had the highest homology which were over 99.5% with the sequences of the reported P. agglomerans (e-Xtra 1, g) . A phylogenetic analysis based on 16S rDNA and gyrB gene sequences was performed using the MEGA6.0 proximity method, and the results of the phylogenetic tree showed that strains Cx1, WH1 and HJ1 clustered on the same clade with the reported P. agglomerans strains (e-Xtra 1, h-j). Thus, Cx1, WH1 and HJ1 were identified as P. agglomerans. Pathogenicity test was performed to complete Koch's postulates, Ningchun 50 was planted in pots, four-week-old healthy wheat seedlings were inoculated with 107 CFU/mL bacterial suspension using two inoculation methods: 1) Leaf surface was poked with disposable syringe needle, and 50 µL of suspension was injected into each of the pinholes (Suraj, S., et al. 2020); 2) Leaf was cut at 45° at the lower 2-3 cm of the leaf tip with scissors dipped in the bacterial suspension. Wheat leaves inoculated with sterile distilled water were regarded as controls. The inoculated wheat was cultivated in a greenhouse (temperature 28 ± 2°C, humidity 40 ± 2%) and covered in transparent polyethylene bags at first 96 h. Symptoms appeared at 3 days after inoculation, and after 7 days, the acupunctured wheat leaves turned chlorotic and yellow around the pinholes and some were necrotic; the leaf-cutting wheat turned yellow and necrotic from the clipping point to the leaf base; the acupunctured and cut leaves totally died after 15 days, and all of the control leaves were healthy (e-Xtra 1, e-f). Subsequently, pathogens were reisolated from inoculated leaves, and identified as P. agglomerans according to molecular identification described above. To our knowledge, this is the first report of leaf blight disease of wheat caused by Pantoea agglomerans globally as well as in China. Identifying the cause of the disease will support efforts for its future control and management.

Design, Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments.

Plant diseases that are caused by fungi and nematodes have become increasingly serious in recent years. However, there are few pesticide chemicals that can be used for the joint control of fungi and nematodes on the market. To solve this problem, a series of novel 1,2,4-oxadiazole derivatives containing amide fragments were designed and synthesized. Additionally, the bioassays revealed that the compound F15 demonstrated excellent antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum) in vitro, and the EC50 value of that was 2.9 µg/mL, which is comparable with commonly used fungicides thifluzamide and fluopyram. Meanwhile, F15 demonstrated excellent curative and protective activity against S. sclerotiorum-infected cole in vivo. The scanning electron microscopy results showed that the hyphae of S. sclerotiorum treated with F15 became abnormally collapsed and shriveled, thereby inhibiting the growth of the hyphae. Furthermore, F15 exhibited favorable inhibition against the succinate dehydrogenase (SDH) of the S. sclerotiorum (IC50 = 12.5 µg/mL), and the combination mode and binding ability between compound F15 and SDH were confirmed by molecular docking. In addition, compound F11 showed excellent nematicidal activity against Meloidogyne incognita at 200 µg/mL, the corrected mortality rate was 93.2%, which is higher than that of tioxazafen.

Age-related differences in corneal nerve regeneration after SMILE and the mechanism revealed by metabolomics.

PURPOSE: To investigate the effect of age on wound healing after small incision lenticule extraction (SMILE) and the underlying metabolomic mechanisms. METHODS: This prospective study was conducted on 216 patients in four groups: the 18-20 (n = 38, Group I), 21-30 (n = 84, Group Ⅱ), 31-40 (n = 58, Group Ⅲ), and 41-50 (n = 36, Group IV) age groups. The density of corneal epithelial wing cells, basal cells, corneal stromal cells, endothelial cells and corneal nerves were examined with a laser confocal microscope (HRT III-RCM) before and 1 month, 3 month, 6 month and 1 year after SMILE. The central nerve fiber length (CNFL), the central corneal nerve fibre density (CNFD), and the central corneal nerve branch density (CNBD) were analyzed by Nero J. The corneal stroma lenticules were obtained from SMILE to analyze metabolites by high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS). RESULTS: The density of corneal wing epithelial cells and basal epithelial cells have no significant difference among the four groups. The CNFL was 21.90 ± 1.68 mm/mm2 in Group Ⅰ and 21.63 ± 2.09 mm/mm2 in Group Ⅱ after 1 year of SMILE, which represented a return to the preoperative level, whereas the CNFL of Group Ⅲ (19.40 ± 0.98 mm/mm2) and Group Ⅳ (18.94 ± 0.72 mm/mm2) were lower than that preoperation (P ˂0.01). CNFL repair had a negative correlation with age after surgery (Pearson's R = -0.572, P ˂0.01). The CNFD and the CNBD showed the same trend with the CNFL (Pearson's R = -0.602 and -0.531, P ˂0.05). Through screening the significantly different metabolites between the 18-30 age group (including Group I and Group Ⅱ) and other two groups, 6 common remarkably different metabolites were identified. Meanwhile, 5 unique different metabolites were identified only between the 18-30 age group and the 31-40 age group. Six unique different metabolites were identified only between the 18-30 age group and the 41-50 age group. CONCLUSION: Corneal nerve repair after SMILE was significantly affected by age. The identified age-associated differences in metabolites were mainly related to inflammation, oxidation, nerve protection and regeneration.

Changes of air quality and its associated health and economic burden in 31 provincial capital cities in China during COVID-19 pandemic.

With outbreak of the novel coronavirus disease (COVID-19), immediate prevention and control actions were imposed in China. Here, we conducted a timely investigation on the changes of air quality, associated health burden and economic loss during the COVID-19 pandemic (January 1 to May 2, 2020). We found an overall improvement of air quality by analyzing data from 31 provincial cities, due to varying degrees of NO2, PM2.5, PM10 and CO reductions outweighing the significant O3 increase. Such improvement corresponds to a total avoided premature mortality of 9410 (7273-11,144) in the 31 cities by comparing the health burdens between 2019 and 2020. NO2 reduction was the largest contributor (55%) to this health benefit, far exceeding PM2.5 (10.9%) and PM10 (23.9%). O3 instead was the only negative factor among six pollutants. The period with the largest daily avoided deaths was rather not the period with strict lockdown but that during February 25 to March 31, due to largest reduction of NO2 and smallest increase of O3. Southwest, Central and East China were regions with relatively high daily avoided deaths, while for some cities in Northeast China, the air pollution was even worse, therefore could cause more deaths than 2019. Correspondingly, the avoided health economic loss attributable to air quality improvement was 19.4 (15.0-23.0) billion. Its distribution was generally similar to results of health burden, except that due to regional differences in willingness to pay to reduce risks of premature deaths, East China became the region with largest daily avoided economic loss. Our results here quantitatively assess the effects of short-term control measures on changes of air quality as well as its associated health and economic burden, and such information is beneficial to future air pollution control.

LncRNA Gm4419 Regulates Myocardial Ischemia/Reperfusion Injury Through Targeting the miR-682/TRAF3 Axis.

Myocardial cell death during acute myocardial infarction occurs because of acute ischemia, persistent ischemia, reperfusion-associated injury, and the inflammatory infiltrate as a response to cell necrosis. In the present study, quantitative real-time PCR showed that lncRNA Gm4419 was highly upregulated in ischemia/reperfusion myocardial tissues and hypoxia/reoxygenation H9C2 cells, whereas miR-682 was downregulated. Knocking down Gm4419 with sh-Gm4419 resulted in the rescue of myocardial infarction and apoptosis induced by ischemia/reperfusion or hypoxia/reoxygenation. Our study further demonstrated that Gm4419 may bind with miR-682 directly. Moreover, in vitro experiments further demonstrated that miR-682 could bind to tumor necrosis factor receptor-associated factor 3 (TRAF3) directly. Most importantly, TRAF3 overexpression could counteract the effect of sh-Gm4419. Taken together, our study indicated that Gm4419 may target miR-682 via sponging to increase TRAF3 expression, thereby contributing to myocardial I/R injury. Therefore, the Gm4419/miR-682/TRAF3 axis may be an important regulatory mechanism in myocardial ischemia/reperfusion injury.

LINC02499, a novel liver-specific long non-coding RNA with potential diagnostic and prognostic value, inhibits hepatocellular carcinoma cell proliferation, migration, and invasion.

AIM: Liver-specific non-coding RNAs have been reported to play crucial roles in hepatocellular carcinoma (HCC). We investigated the possible biological performance of a novel liver-specific long non-coding RNA, LINC02499, in HCC. METHODS: The association between LINC02499 expression and HCC was evaluated based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and then confirmed in a HCC cohort by quantitative real-time polymerase chain reaction. The effects of LINC02499 on HCC cells were verified by gain- and loss-of-function assays. Pathway enrichment analyses were used to explore the potential mechanism of LINC02499 in HCC. RESULTS: LINC02499 expression was remarkably decreased in HCC tissues compared to adjacent non-tumor tissues based on TCGA (P < 0.001) and GEO databases (P < 0.001) and our HCC cohort (P < 0.001). Decreased LINC02499 was also significantly associated with poorer overall survival in both the TCGA database (P = 0.009) and our HCC cohort (P = 0.002). Furthermore, the receiver operating characteristic analysis indicated that LINC02499 showed a good performance in HCC diagnosis (area under the curve = 0.879, P < 0.001), and both sensitivity and specificity were 83.8%. In addition, up- and downregulated LINC02499 significantly impacted proliferation, migration, and invasion abilities of HCC cells in vitro. Pathway enrichment analyses revealed that the potential target genes of LINC02499 were involved in "Complement and coagulation cascades" and "Butanoate metabolism" pathways. CONCLUSION: LINC02499 could be a potential novel diagnostic and prognostic biomarker for HCC patients, and it could exert a tumor suppressor role in the progression of HCC.

Novel mutations of AXIN2 identified in a Chinese Congenital Heart Disease Cohort.

Congenital heart defects (CHDs), the most common congenital human birth anomalies, involves complex genetic factors. Wnt/ß-catenin pathway is critical for cardiogenesis and proved to be associated with numerous congenital heart abnormities. AXIN2 has a unique role in Wnt/ß-catenin pathway, as it is not only an important inhibitor but also a direct target of Wnt/ß-catenin pathway. However, whether AXIN2 is associated with human CHDs has not been reported. In our present study, we found a differential expression of Axin2 mRNA during the development of mouse heart, indicating its importance in mouse cardiac development. Then using targeted next-generation sequencing, we found two novel case-specific rare mutations [c.28 C > T (p.L10F), c.395 A > G (p.K132R)] in the sequencing region of AXIN2. In vitro functional analysis suggested that L10F might be a loss-of-function mutation and K132R is a gain-of-function mutation. Both mutations disrupted Wnt/ß-catenin pathway and failed to rescue CHD phenotype caused by Axin2 knockdown in zebrafish model. Collectively, our study indicates that rare mutations in AXIN2 might contribute to the risk of human CHDs and a balanced canonical Wnt pathway is critical for cardiac development process. To our knowledge, it is the first study of AXIN2 mutations associated with human CHDs, providing new insights into CHD etiology.