Based on molecular docking and real-time PCR technology, the two-component system Bae SR was investigated on the mechanism of drug resistance in CRAB.

This study aimed to explore the role of the two-component system Bae SR in the mechanism of drug resistance in carbapenem-resistant A. baumannii (CRAB) using molecular docking and real-time polymerase chain reaction (PCR). The two-component system Bae SR of Acinetobacter baumannii was subjected to molecular docking with imipenem, meropenem, and levofloxacin. Antibacterial assays and fluorescence quantitative PCR were used to explore protein-ligand interactions and molecular biological resistance mechanisms related to CRAB. The analysis of the two-component system in A. baumannii revealed that imipenem exhibited the highest docking energy in Bae S at - 5.81 kcal/mol, while the docking energy for meropenem was - 4.92 kcal/mol. For Bae R, imipenem had a maximum docking energy of - 4.28 kcal/mol, compared with - 4.60 kcal/mol for meropenem. The highest binding energies for Bae S-levofloxacin and Bae R-levofloxacin were - 3.60 and - 3.65 kcal/mol, respectively. All imipenem-resistant strains had minimum inhibitory concentration (MIC) values of 16 µg/mL, whereas levofloxacin-resistant strains had MIC values of 8 µg/mL. The time-sterilization curve showed a significant decrease in bacterial colony numbers at 2 h under the action of 8 µg/mL imipenem, indicating antibacterial effects. In contrast, levofloxacin did not exhibit any antibacterial activity. Fluorescence quantitative PCR results revealed significantly increased relative expression levels of bae S and bae R genes in the CRAB group, which were 2 and 1.5 times higher than those in the CSAB group, respectively, with statistically significant differences. Molecular docking in this study found that the combination of Bae SR and carbapenem antibiotics (imipenem, meropenem) exhibited stronger affinity and stability compared with levofloxacin. Moreover, the overexpression of the two-component system genes in carbapenem-resistant A. baumannii enhanced its resistance to carbapenem, providing theoretical and practical insights into carbapenem resistance in respiratory tract infections caused by A. baumannii.

Corrigendum: Ribosomal protein L23 drives the metastasis of hepatocellular carcinoma via upregulating MMP9.

[This corrects the article DOI: 10.3389/fonc.2021.779748.].

RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling.

BACKGROUND: Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. METHODS: By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9-mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. RESULTS: Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155-3375 region of the 3'UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. CONCLUSIONS: Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.

Tai Chi Effects on Heart Rate Variability: A Systematic Review and Meta-Analysis.

Background: Tai Chi, originating in China, is a mind-body exercise that integrates mind training, Qi training, and body training. While Tai Chi practice has demonstrated beneficial physical and psychological health benefits, how it achieves effects has been less studied. In recent years, some researchers have begun to explore the potential of heart rate variability (HRV) changes as balancing the autonomic nervous system (ANS) to achieve results, but only a few studies have directly tested how Tai Chi impacts HRV, and results have been mixed. Objective: This study systematically evaluates the effects of Tai Chi on HRV. Methods: Electronic databases including Web of Science, PubMed, Scopus, Cochrane Library, and EBSCOhost direct from inception until December 2020 were searched to obtain eligible studies. The primary outcomes examined were HRV parameters (time domain and frequency domain), and secondary analysis was whether breathing was emphasized during Tai Chi interventions. Results: Based on the 11 randomized controlled trials included comparing Tai Chi with non-active control condition, meta-analyses showed significantly beneficial effects on HRV parameters (low-frequency power [LF], mean difference [MD] = -200.40, 95% confidence interval [CI]: 365.31 to -35.49, p = 0.02; normalized low-frequency power [nLF], MD = -7.39, 95% CI: -12.48 to -2.29, p = 0.004; total power [TP], MD = -649.82, 95% CI: -1180.54 to -119.11, p = 0.02; very low-frequency power [VLF], MD = -200.55, 95% CI: -349.63 to -51.46, p = 0.008; root mean square of the square sum of the difference between adjacent normal heartbeat intervals [RMSSD], MD = 2.59, 95% CI: -7.23 to 12.41, p < 0.0001; standard deviation of the heartbeat interval [SDNN], MD = 8.33, 95% CI: 0.69 to 15.98, p = 0.03). The effect of Tai Chi on certain HRV parameters compared with active control conditions was less favorable (nLF, MD = 6.42, 95% CI: 3.74 to 9.09, p < 0.00001; normalized high-frequency power [nHF], MD: -6.13, 95% CI: -8.76 to -3.50, p < 0.00001; low-frequency/high-frequency power ratio [LF/HF], MD = 1.00, 95% CI: 0.68 to 1.33, p < 0.00001). In addition, studies describing an emphasis on breathing in the Tai Chi intervention showed positive impact on HRV (nLF, MD = -3.22, 95% CI: -5.32 to -1.12, p = 0.003; nHF, MD = 3.80, 95% CI: 0.80 to 6.81, p = 0.01; SDNN, MD = 5.55, 95% CI: 4.85 to 6.25, p < 0.00001). Conclusions: Meta-analysis results showed that Tai Chi compared with non-active control conditions has a positive impact on key HRV parameters associated with the ANS balance. However, active control condition comparisons showed greater HRV improvements than for Tai Chi. Considering the limited number of studies and their heterogeneity, further robust studies are necessary to verify findings and investigate differential effects of Tai Chi on HRV.

Clinical Features, Diagnosis, and Treatment of Congenital and Neonatal Tuberculosis: A Retrospective Study.

INTRODUCTION: Limited studies have explored the clinical features, treatment, and prognosis of neonatal tuberculosis (TB). Here, we attempted to delineate the clinical characteristics of neonatal TB, which may help clinicians further understand this disease. METHODS: A retrospective analysis of neonates diagnosed with congenital and/or neonatal TB disease from January 2010 to December 2020 was performed. Information on the demographic and epidemiological features, clinical symptoms, laboratory and imaging examinations, therapeutic regimens, and outcomes was collected. Kaplan-Meier analysis was used to present the time to disease onset, time to diagnosis, etc. Results: Forty-eight cases of neonatal TB were classified into congenital (n = 33) and postnatal (n = 15). The median time to disease onset in postnatal group was significantly longer than that in congenital group. Positive results for gastric fluid acid-fast bacilli, TB culture, Xpert MTB/RIF, interferon-γ release assay (IGRA), and tuberculin skin test were detected in 26/48 (54.2%), 14/34 (41.2%), 11/18 (61.1%), 19/29 (65.5%), and 8/24 (33.3%) patients, respectively. For lymphadenopathy, computed tomography (CT) scans showed a higher detection rate than did X-ray (80.0% vs. 0). Of the 48 infants, 44/48 (91.7%) received anti-TB therapy, and 33/44 (75%) were clinically improved or cured after 22.1 months (interquartile range: 12.4-27.7) of follow-up. Drug-induced liver injury occurred in 14/44 (31.8%) patients. DISCUSSION/CONCLUSION: IGRA and Xpert MTB/RIF showed good positive rate in neonatal TB infection/disease. In cases where TB is presumed but etiological evidence is lacking, low-dose CT could be considered. Prompt treatment under careful surveillance is important for preventing mortality and avoiding severe adverse effects.

Er3+ doped nanoparticles as upconversion thermometer probes in confined fluids.

Non-contact temperature measurement at the nanoscale by photoluminescence using a nano-sensor in a confined fluid has been performed in the present work. Upconversion lanthanide-doped nanoparticles applied to ratiometric thermometry could be considered as a self-referenced nanosensor. Gadolinium orthovanadate (GdVO4) nanoparticles doped with Yb3+ and Er3+ were synthesized and then dispersed in an ester-based fluid. Rheological measurements show that the viscosity of the dispersed NP suspension remains unchanged up to a shear rate of 10-4 s-1 at 393 K. The NP suspension allows luminescence intensity ratio (LIR) thermometry up to 473 K with a relative sensitivity of 1.17% K-1 with a NIR laser. Then, the temperature calibration by coupling the high pressure (1.08 GPa max) confirmed the applicability of NPs as a thermosensor in a variable pressure environment. According to these results, the fluid containing GdVO4:Yb3+/Er3+ nanoparticles can be used for temperature sensing in a pressurized environment for further application in tribology.

Epicardial adipose tissue density is a better predictor of cardiometabolic risk in HFpEF patients: a prospective cohort study.

BACKGROUND: Epicardial adipose tissue (EAT) accumulation is associated with multiple cardiometabolic risk factors and prognosis of heart failure with preserved ejection fraction (HFpEF). The correlation between EAT density and cardiometabolic risk and the effect of EAT density on clinical outcome in HFpEF remain unclear. We evaluated the relationship between EAT density and cardiometabolic risk factors, also the prognostic value of EAT density in patients with HFpEF. METHODS: We included 154 HFpEF patients who underwent noncontrast cardiac computed tomography (CT) and all patients received follow-up. EAT density and volume were quantified semi-automatically. The associations of EAT density and volume with cardiometabolic risk factors, metabolic syndrome and the prognostic impact of EAT density were analyzed. RESULTS: Lower EAT density was associated with adverse changes in cardiometabolic risk factors. Each 1 HU increase in fat density, BMI was 0.14 kg/m2 lower (95% CI 0.08-0.21), waist circumference was 0.34 cm lower (95% CI 0.12-0.55), non-HDL-cholesterol was 0.02 mmol/L lower (95% CI 0-0.04), triglyceride was 0.03 mmol/L lower (95% CI 0.01-0.04), fasting plasma glucose was 0.05 mmol/L lower (95% CI 0.02-0.08), TyG index was 0.03 lower (95% CI 0.02-0.04), Log2(TG/HDL-C) was 0.03 lower (95% CI 0.02-0.05), METS-IR was 0.36 lower (95% CI 0.23-0.49), MetS Z-score was 0.04 lower (95% CI 0.02-0.06), and Log2(CACS + 1) was 0.09 lower (95% CI 0.02-0.15). After adjusting for BMI and EAT volume, the associations of non-HDL-cholesterol, triglyceride, fasting plasma glucose, insulin resistance indexes, MetS Z-score, and CACS with fat density remained significant. The area under the curve (AUC) for the presence and severity of metabolic syndrome was greater in EAT density than volume (AUC: 0.731 vs 0.694, 0.735 vs 0.662, respectively). Over a median follow-up of 16 months, the cumulative incidence of heart failure readmission and composite endpoint increased with lower level of EAT density (both p < 0.05). CONCLUSIONS: EAT density was an independent impact factor of cardiometabolic risk in HFpEF. EAT density might have better predictive value than EAT volume for metabolic syndrome and it might have prognostic value in patients with HFpEF.

Impact of digital finance on energy efficiency: empirical findings from China.

The world is facing the problem of resource scarcity and environmental degradation. Improving energy efficiency is an effective way to reduce energy consumption and reduce pollutant emissions. Based on relevant data from 30 Chinese provinces from 2011 to 2019, this paper constructs energy efficiency indicators by establishing a super-efficient three-stage SBM-DEA model. It explores the impact of digital finance on energy efficiency using a systematic generalized moment estimation method and constructs an analytical framework for the impact of digital inclusive finance on energy efficiency from the breadth of coverage, depth of use, and degree of digitization of digital inclusive finance. In addition, this paper examines the differences in the impact of digital inclusive finance on energy efficiency from a sub-regional perspective. Research indicates the following: (1) At the national level, the relationship between digital inclusive finance development and energy efficiency in China shows an inverted "U"-shape; the breadth of digital financial coverage, the use of digital insurance services and digital credit services, and the degree of digitalization of digital finance all have significant effects on energy efficiency. (2) From a regional perspective, the impact of digital inclusive finance on energy efficiency has regional heterogeneity. Based on this finding, first, the government should speed up the construction of digital financial infrastructure to promote the further development of digital finance. Second, the government should take appropriate measures to regulate industry giants. Third, the government should adjust measures to local conditions when formulating policies. The above research has certain implications for improving the targeting of digital finance-related policies and promoting the high-quality development of China's economy.

Brassinosteroids mediate moderate soil-drying to alleviate spikelet degeneration under high temperature during meiosis of rice.

This study tested the hypothesis that brassinosteroids (BRs) mediate moderate soil-drying (MD) to alleviate spikelet degeneration under high temperature (HT) stress during meiosis of rice (Oryza sativa L.). A rice cultivar was pot-grown and subjected to normal temperature (NT) and HT treatments during meiosis, and two irrigation regimes including well-watered (WW) and MD were imposed to the plants simultaneously. The MD effectively alleviated the spikelet degeneration and yield loss under HT stress mainly via improving root activity and canopy and panicle traits including higher photosynthetic capacity, tricarboxylic acid cycle activity, and antioxidant capacity than WW. These parameters were regulated by BRs levels in plants. The decrease in BRs levels at HT was due mainly to the enhanced BRs decomposition, and the MD could rescue the BRs deficiency at HT via enhancing BRs biosynthesis and impeding decomposition. The connection between BRs and HT was verified by using rice BRs-deficient mutants, transgenic rice lines, and chemical regulators. Similar results were obtained in the open-air field experiment. The results suggest that BRs can mediate the MD to alleviate spikelet degeneration under HT stress during meiosis mainly via enhancing root activity, canopy traits, and young panicle traits of rice.

Case report: A case of severe acute hepatitis of unknown origin.

According to analyses of etiology, clinical features, diagnostic methods, and treatment strategies by summarizing a case of unexplained acute hepatitis recently experienced, we are aiming to provide some information to enrich the clinical experience in diagnosis and treatment of severe acute hepatitis of unknown etiology in young children. A boy, aged 10 years and 6 months old, was admitted to the hospital due to acute abdominal pain, jaundice, and exceptionally high levels of ALT and AST. A range of measures, including patient history, physical examination, and routine laboratory testing, were performed. Furthermore, strategies such as trio-based next-generation sequencing (Trio-NGS) and liver biopsy, as well as metagenomic NGS (mNGS) of blood and liver samples were also performed. In summary, this case was an acute severe non-A-E hepatitis that is a probable case with hepatitis of unknown origin. Immunohistochemical analysis showed an immune injury in liver tissues. Torque teno virus (TTV) sequences were detected by mNGS assay. As for treatment strategies, in addition to general treatment, this patient also underwent plasmapheresis and methylprednisolone treatment due to disease deterioration. The patient's liver function was improved afterward and discharged after one month of treatment. Taken together, this work reported the clinical feature and treatment of severe acute hepatitis with non-A-E hepatitis in detail. The potential mechanism of liver damage might be due to an immune attack in which TTV might play a role as a co-factor.

The Comparison of Metagenomic Next-Generation Sequencing with Conventional Microbiological Tests for Identification of Pathogens and Antibiotic Resistance Genes in Infectious Diseases.

Background: Metagenomic next-generation sequencing (mNGS) has been widely studied, due to its ability of detecting all the microbial genetic information unbiasedly in a sample at one time and not relying on traditional culture. However, the application of mNGS in the diagnosis of clinical pathogens remains challenging. Methods: From December 2019 to March 2021, 134 specimens including Broncho alveolar lavage fluid (BAFL), blood, sputum, cerebrospinal fluid (CSF), bile, pleural fluid, pus, were continuously collected in The First Hospital of Qinhuangdao, and their retrospective diagnoses were classified into infectious disease (128, 95.5%) and noninfectious disease (6, 4.5%). The pathogen-detection performance of mNGS was compared with conventional microbiological tests (CMT) and culture method. In addition, the antibiotic resistance genes (ARGs) and evolutionary relationship of common drug-resistant A. baumannii were also analyzed. Results: Compared with CMT and culture methods, mNGS showed higher sensitivity in pathogen detection (74.2% vs 57.8%; P < 0.001 and 66.3% vs 31.7%; P < 0.001, respectively). Importantly, for cases that mNGS-positive only, 18 (35%) cases result in diagnosis modification, and 7 (23%) cases confirmed the clinical diagnosis. In 17 cases that A. baumannii were both detected in mNGS and culture, ade genes were the most frequently detected ARGs (from 13 cases), followed by sul2 and APH(3")-Ib (both from 12 cases). High consistency was observed among these ARGs and the related phenotype (100% for ade genes, 91.6% for sul2 and APH(3")-Ib). A. baumannii strains were classified into three groups, and most were well-clustered. It suggested those strains may be the epidemic strains. Conclusion: In our study, mNGS had a higher sensitivity than CMT and culture method. And the result of ARGs frequency and cluster analysis of A. baumannii was of great significance to the anti-infective therapy.

Chinese endemic medicinal plant Bolbostemma paniculatum (Maxim.) Franquet: A comprehensive review.

Bolbostemma paniculatum (Maxim.) Franquet is a unique species in China with a long history of medicinal use, which has the effects of detoxifying, dissolving lumps and dispersing swellings. And it is commonly used to treat many diseases, such as carbuncle and sore, acute mastitis, mammary cancer, scrofula and subcutaneous nodule traditionally. Modern clinical studies have found that B. paniculatum and its compounds can be used for the treatment of a variety of cancers, mastitis, hyperplasia of mammary glands, chronic lymphadenitis, cervical lymph tuberculosis and surgical wart skin diseases, and the curative effect is positive. At present, a variety of Chinese patent medicines containing B. paniculatum have been exploited and marketed in China for the treatment of cancers, breast diseases and flat warts. This review article comprehensively discussed the traditional application, botany, chemical components, pharmacological activities, and quality control of B. paniculatum, put forward some noteworthy issues and suggestions in current studies, and briefly discussed the possible development potential of this plant as well as future research perspectives. 96 compounds have been isolated from B. paniculatum, including triterpenoids, sterols, alkaloids and other components, of which triterpenoid saponins are the main bioactive components. The crude extracts and monomer compounds of B. paniculatum have a wide range of pharmacological activities, such as anti-tumor, antiviral, anti-inflammatory, immunoregulatory, and so on. Moreover, its anti-tumor mechanism involves many aspects, including inhibiting cell proliferation, promoting cell apoptosis, blocking the cell cycle, interfering with cell invasion and metastasis, suppressing angiogenesis, and regulating autophagy. While there is a lack of systematic and in-depth research on its anti-tumor active components and mechanism of action at the moment; and a tight connection between the chemical composition and pharmacological activity of B. paniculatum has also not been established. Besides, a systematic quality determination standard for B. paniculatum should also be built, in order to carry out further research.

Amino Acids in Rice Grains and Their Regulation by Polyamines and Phytohormones.

Rice is one of the most important food crops in the world, and amino acids in rice grains are major nutrition sources for the people in countries where rice is the staple food. Phytohormones and plant growth regulators play vital roles in regulating the biosynthesis of amino acids in plants. This paper reviewed the content and compositions of amino acids and their distribution in different parts of ripe rice grains, and the biosynthesis and metabolism of amino acids and their regulation by polyamines (PAs) and phytohormones in filling grains, with a focus on the roles of higher PAs (spermidine and spermine), ethylene, and brassinosteroids (BRs) in this regulation. Recent studies have shown that higher PAs and BRs (24-epibrassinolide and 28-homobrassinolide) play positive roles in mediating the biosynthesis of amino acids in rice grains, mainly by enhancing the activities of the enzymes involved in amino acid biosynthesis and sucrose-to-starch conversion and maintaining redox homeostasis. In contrast, ethylene may impede amino acid biosynthesis by inhibiting the activities of the enzymes involved in amino acid biosynthesis and elevating reactive oxygen species. Further research is needed to unravel the temporal and spatial distribution characteristics of the content and compositions of amino acids in the filling grain and their relationship with the content and compositions of amino acids in different parts of a ripe grain, to elucidate the cross-talk between or among phytohormones in mediating the anabolism of amino acids, and to establish the regulation techniques for promoting the biosynthesis of amino acids in rice grains.

SIRT2 Promotes HBV Transcription and Replication by Targeting Transcription Factor p53 to Increase the Activities of HBV Enhancers and Promoters.

Chronic hepatitis B (CHB) virus infection is one of the leading causes of cirrhosis and liver cancer. Although the major drugs against CHB including nucleos(t)ide analogs and PEG-interferon can effectively control human hepatitis B virus (HBV) infection, complete cure of HBV infection is quite rare. Targeting host factors involved in the viral life cycle contributes to developing innovative therapeutic strategies to improve HBV clearance. In this study, we found that the mRNA and protein levels of SIRT2, a class III histone deacetylase, were significantly upregulated in CHB patients, and that SIRT2 protein level was positively correlated with HBV viral load, HBsAg/HBeAg levels, HBcrAg, and ALT/AST levels. Functional analysis confirmed that ectopic SIRT2 overexpression markedly increased total HBV RNAs, 3.5-kb RNA and HBV core DNA in HBV-infected HepG2-Na+/taurocholate cotransporting polypeptide cells and primary human hepatocytes. In contrast, SIRT2 silencing inhibited HBV transcription and replication. In addition, we found a positive correlation between SIRT2 expression and HBV RNAs synthesis as well as HBV covalently closed circular DNA transcriptional activity. A mechanistic study suggested that SIRT2 enhances the activities of HBV enhancer I/HBx promoter (EnI/Xp) and enhancer II/HBc promoter (EnII/Cp) by targeting the transcription factor p53. The levels of HBV EnI/Xp and EnII/Cp-bound p53 were modulated by SIRT2. Both the mutation of p53 binding sites in EnI/Xp and EnII/Cp as well as overexpression of p53 abolished the effect of SIRT2 on HBV transcription and replication. In conclusion, our study reveals that, in terms of host factors, a SIRT2-targeted program might be a more effective therapeutic strategy for HBV infection.

Pimobendan Inhibits HBV Transcription and Replication by Suppressing HBV Promoters Activity.

Current anti-HBV therapeutic strategy relies on interferon and nucleos(t)ide-type drugs with the limitation of functional cure, inducing hepatitis B surface antigen (HBsAg) loss in very few patients. Notably, the level of HBsAg has been established as an accurate indicator to evaluate the drug efficacy and predict the disease prognosis, thus exploring a novel drug targeting HBsAg will be of great significance. Herein, by screening 978 compounds from an FDA-approved drug library and determining the inhibitory function of each drug on HBsAg level in HepG2.2.15 cells supernatant, we identified that pimobendan (Pim) has a powerful antiviral activity with relatively low cytotoxicity. The inhibitory effect of Pim on HBsAg as well as other HBV markers was validated in HBV-infected cell models and HBV-transgenic mice. Mechanistically, real-time PCR and dual-luciferase reporter assay were applied to identify the partial correlation of transcription factor CAAT enhancer-binding protein α (C/EBPα) with the cccDNA transcription regulated by Pim. This indicates Pim is an inhibitor of HBV transcription through suppressing HBV promoters to reduce HBV RNAs levels and HBsAg production. In conclusion, Pim was identified to be a transcription inhibitor of cccDNA, thereby inhibiting HBsAg and other HBV replicative intermediates both in vitro and in vivo. This report may provide a promising lead for the development of new anti-HBV agent.

Agricultural Openness and the Risk of COVID-19 Incidence: Evidence from China.

At present, there are large number of articles on the impact of COVID-19, but there are only a few articles on the impact of COVID-19 and international agriculture. Agriculture product is different from other industrial products. If domestic food cannot be self-sufficient, it must be resolved through imports. This will inevitably face the dilemma between the opening up agriculture and the risk of importing COVID-19. This paper pioneered the use of entropy method, TOPSIS method and grey correlation analysis to predict the correlation between agricultural opening to the outside world and the input and spread of COVID-19. We use the correlation matrix quantifying the number of confirmed COVID-19 cases and agricultural openness to deduce that there is a significant positive correlation between the flow of agricultural products caused by China's agricultural opening-up and the spread of COVID-19, and use the proposed matrix to predict the spread risk of COVID-19 in China. The results of the empirical analysis can provide strong evidence for decision-makers to balance the risk of COVID-19 transmission with the opening of agricultural markets, and they can take this evidence into full consideration to formulate reasonable policies. This has great implications both for preventing the spread of COVID-19 and for agricultural opening-up.

Drag Effect of Economic Growth and Its Spatial Differences under the Constraints of Resources and Environment: Empirical Findings from China's Yellow River Basin.

As the global economic development intensifies the plunder of resources and the environment, the constraints are becoming more and more obvious. Based on the background of the strategy for ecological conservation and high-quality development of the Yellow River Basin, this paper intends to construct a resource-environment-constrained economic growth drag effect model and a spatial Dubin model, and explore the economic growth drag effect and its spatial differences in the Yellow River Basin under the constraints of resources and environment. The study found that the total drag effects of the overall economic growth of the Yellow River Basin that were obtained by the classic panel model without spatial effects is significantly negative. This is consistent with the conclusion that the average total drag effects of 80 prefecture-level cities is negative. The total drag effects of the overall economic growth of the Yellow River Basin changes from unconstrained to medium-constrained after adding spatial constraints, indicating that the spatial correlation of factors will restrict economic growth. From the level of the Yellow River sub-catchment, the total drag effect of the direct effects of the upper, middle, and lower reaches of the Yellow River is consistent with the total drag effect of the total effect. It shows that the upper economic growth is strongly constrained by the local resources and environment, while the downstream is strongly constrained by the adjacent resources and the environment. The research results provide references for resolving the resources and environment constraints in the Yellow River Basin. It provides useful inspiration for promoting ecological protection and high-quality development strategies in the Yellow River Basin.

Glutamate dehydrogenase 1 mediated glutaminolysis sustains HCC cells survival under glucose deprivation.

Besides aerobic glycolysis, glutaminolysis has also become a hot spot in the field of tumor research because of its important role in regulating cell proliferation, apoptosis, and migration and invasion. Meanwhile, it is generally believed that tumor cells could sustain its proliferation and survival according to a so-called metabolic flexibility. How the metabolic flexibility of HCC cells behaves has not yet been fully elucidated. In this study, we validated the glutamine addiction of HCC cells, and identified that the glutaminolysis pathway of HCC cells altered in response to different glucose conditions. That is, glutamate transaminases GOT1 pathway played a dominant role in regulating cell growth when glucose was sufficient, yet deaminase GDH1 mediated metabolic pathway became dominant when glucose was limited, for the reason that GDH1 could drive the TCA cycle in response to glucose deprivation. Additionally, we further uncovered an negative relationship between GDH1 and GOT1 in low-glucose HCC tissues. Together, our study provided a new insight into the metabolic flexibility of glutaminolysis related enzymes in HCC, and highlighted the crucial role of GDH1 on HCC cells proliferation and survival in glucose starvation.

DDX17-regulated alternative splicing that produced an oncogenic isoform of PXN-AS1 to promote HCC metastasis.

BACKGROUND AND AIMS: The mechanism underlying HCC metastasis remains unclear, many oncogenes are known to regulate this process. However, the role of alternative splicing (AS) in pro-metastatic HCC is poorly understood. APPROACH AND RESULTS: By performing RNA sequencing on nine pairs of primary HCC tissues with extrahepatic metastasis (EHMH) and nine pairs of metastasis-free HCC (MFH) tissues, we depicted the AS landscape in HCC and found a higher frequency of AS events in EHMH compared with MFH. Moreover, 28 differentially expressed splicing regulators were identified in EHMH compared with MFH. Among these, DEAD-box RNA helicase 17 (DDX17) was significantly up-regulated in EHMH and was strongly associated with patient outcome. Functional studies indicated that DDX17 knockout inhibited the degradation of the extracellular matrix, and diminished the invasive ability of HCC cells. A significant reduction in lung metastasis induced by DDX17 deficiency was also demonstrated in a diethylnitrosamine-induced DDX17HKO mouse model. Mechanistically, high DDX17 induced intron 3 retention of PXN-AS1 and produced a transcript (termed PXN-AS1-IR3). The transcript PXN-AS1-IR3 acted as an important promoter of HCC metastasis by inducing MYC transcription activation via recruiting the complex of testis expressed 10 and p300 to the MYC enhancer region, which led to transcriptional activation of several metastasis-associated downstream genes. Finally, the PXN-AS1-IR3 level was significantly higher in serum and HCC tissues with extrahepatic metastasis. CONCLUSIONS: DDX17 and PXN-AS1-IR3 act as important metastatic promoters by modulating MYC signaling, suggesting that DDX17 and PXN-AS1-IR3 may be potential prognostic markers for metastatic HCC.