Effects of Short-Term Tillage on Rhizosphere Soil Nitrogen Mineralization and Microbial Community Composition in the Double-Cropping Rice Field.

Soil extracellular enzyme plays a vital role in changing soil nitrogen (N) mineralization of rice field. However, the effects of soil extracellular enzyme activities (EEA) and microbial community composition response to N mineralization of rice field under short-term tillage treatment needed to be further explored. In this study, we investigated the impact of short-term (8-year) tillage practices on rhizosphere soil N transformation rate, soil enzyme activities, soil microorganism community structure and their N mineralization function genes in double-cropping rice field in southern China. The experiment consisted of four tillage treatments: rotary tillage with crop straw input (RT), conventional tillage with crop straw input (CT), no-tillage with crop straw retention (NT), and rotary tillage with all crop straws removed as a control (RTO). The results indicated that rhizosphere soil N transformation rate in paddy field in NT and RTO treatments were significantly lower than that in RT and CT treatments. Compared with NT and RTO treatments, soil protease, urease, ß-glucosaminidase and arginase activities with CT treatment were significantly improved, as were abundances of soil sub, npr and chiA with CT and RT treatments. Moreover, diversity of overall soil bacterial communities in NT and RTO treatments were significantly lower than that in RT and CT treatments. Soil chitinolytic and bacterial ureolytic communities were also obviously changed combined with tillage and crop straw input practices.

Review: Progress towards research on the toxicology of pyrimethanil.

Pyrimethanil is a persistent environmental pollutant that poses a significant threat to human health. In this review, we summarize the fungicidal mechanism of pyrimethanil and its toxicological effects on aquatic organisms and mammals, as well as its impact on growth and development as an endocrine disruptor. Additionally, we investigate the metabolism of pyrimethanil in mammals and its molecular mechanism in the occurrence of Alzheimer's disease. Furthermore, this review outlines the influence of climate change on the toxicity of pyrimethanil, emphasizing the need to consider the impact of mixtures of multiple compounds on human health. Finally, we propose several promising future directions for pyrimethanil research, believing that there is a better understanding of the interaction between pyrimethanil and organisms, as well as the development of techniques to remove pyrimethanil, may be the best approach to eliminating the threat posed by this compound.

Adiponectin inhibits ROS/NLRP3 inflammatory pathway through FOXO3A to ameliorate oral submucosal fibrosis.

Oral submucous fibrosis (OSF) is an oral condition characterized by chronic progression, which may lead to the development of malignancy. Currently, available treatments for OSF only provide temporary relief of symptoms, and there is a limited availability of effective interventions that can effectively cure this condition. In this study, we aimed to investigate whether adiponectin (APN) could ameliorate OSF and the mechanisms involved in it. First, human oral mucosal fibroblasts (HOMFs) were cultured, an OSF model was established using arecoline, and APN and Imiquimod treatment were administered. Then we overexpressed NLRP3 and knocked down FOXO3A. FOXO3A, fibrosis-related factors (ɑ-SMA, COL1A, CTGF), TGF-ß1/Smad3 signaling-related factors (TGF-ß1, p-Smad3, Smad3), NLRP3 inflammasome-related factors (NLRP3, Caspase-1, IL-1ß), and ROS levels were evaluated. Finally, we explored the effect of APN on OSF in mice by in vivo experiments. We found that arecoline significantly increased ɑ-SMA, COL1A, CTGF, and TGF-ß1 expressions and promoted Smad3 phosphorylation, while APN significantly inhibited the elevation of these fibrosis-related factors. ROS production was significantly elevated in HOMFs after arecoline treatment, while APN treatment inhibited ROS production. However, the addition of Imiquimod and overexpression of NLRP3 exhibited a trend of elevated ROS, resisting the inhibitory effect of APN. Furthermore, adding Imiquimod and overexpression of NLRP3 elevated ɑ-SMA, COL1A and CTGF and activated TGF-ß1/Smad3 signaling pathway. Additionally, knockdown of FOXO3A enhanced APN-inhibited ɑ-SMA and COL1A. In vivo experiments further confirmed that APN ameliorated OSF in mice by inhibiting ROS/NLRP3 inflammatory pathway. In conclusion, APN ameliorated arecoline-induced OSF by promoting FOXO3A expression and downregulating the ROS/NLRP3 pathway.

Immediate histologic correlation in patients with different HPV genotypes and ages: a single center analysis in China.

BACKGROUND: Human papillomavirus (HPV) has been confirmed as a major causative factor for malignant transformation of cervical epithelial cells and for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. We carried out this study to investigate the association of different HPV genotypes and ages with immediate histological cervical lesions in opportunistic screening patients in a single center. METHODS: A total of 1,661 samples with biopsy-confirmed histologic findings were collected from the gynecological clinic of our hospital between October 2017 and May 2020 for analysis. The distribution of single-type HPV genotypes in CIN of different severities and the age-dependent prevalence for single-type HPV infection were analyzed. RESULTS: In both CIN2 and CIN3 group, HPV16, 58, 52, 33 and 31/18 were detected as top 5 high-risk human papillomavirus (hrHPV) types, which accounts for 89.25% and 88.54% of single HPV infection incidence respectively. Besides, not a single case of HPV45 was found in CIN2 and CIN3. HPV16 was the dominant genotype in both CIN2 and CIN3, accounted for 46.24% and 55.21%, respectively. The prevalence of HPV16 was the most frequent in all the age groups, except ≥ 65 years group in CIN3, and almost one in three HPV16-positive patients were diagnosed with high grade CIN. The peak of the incidence of CIN3 was observed at 25 ~ 34 years (33.68%), followed by 35 ~ 44 years (31.58%). CONCLUSION: High grade CIN peak at 25 ~ 44 years, women of this age are recommended for normative screening if conditions permit. HPV16-positive patients should be given high priority in opportunistic screening, while the single-center data suggesting a low risk of CIN2/3 in HPV45-positive patients. For women ≥ 65 years old, patients infected with other HPV types should be also taken seriously. In general, HPV16, 58, 52, 33, 31 and 18 were the most common genotypes in CIN2/3, and a vaccine including these predominant genotypes might be of great significance for cervical cancer prevention in China.

Systolic heart failure induced by butylparaben in zebrafish is caused through oxidative stress and immunosuppression.

Due to Butylparaben (BuP) widespread application in cosmetics, food, pharmaceuticals, and its presence as an environmental residue, human and animal exposure to BuP is common, potentially posing hazards to both human and animal health. Congenital heart disease is already a serious problem. However, the effects of BuP on the developing heart and its underlying mechanisms remain unclear. Here, zebrafish embryos were exposed to environmentally and human-relevant concentrations of BuP (0.6 mg/L, 1.2 mg/L, and 1.8 mg/L, calculated but not measured) at 6 h post-fertilization (hpf) and were treated until 72 hpf. Exposure to BuP led to cardiac morphological defects and cardiac dysfunction in zebrafish embryos, manifesting symptoms similar to systolic heart failure. The etiology of BuP-induced systolic heart failure in zebrafish embryos is multifactorial, including cardiomyocyte apoptosis, endocardial and atrioventricular valve damage, insufficient myocardial energy, impaired Ca2+ homeostasis, depletion of cardiac-resident macrophages, cardiac immune non-responsiveness, and cardiac oxidative stress. However, excessive accumulation of reactive oxygen species (ROS) in the cardiac region and cardiac immunosuppression (depletion of cardiac-resident macrophages and cardiac immune non-responsiveness) may be the predominant factors. In conclusion, this study indicates that BuP is a potential hazardous substance that can cause adverse effects on the developing heart and provides evidence and insights into the pathological mechanisms by which BuP leads to cardiac dysfunction. It may help to prevent the BuP-based congenital heart disease heart failure in human through ameliorating strategies and BuP discharge policies, while raising awareness to prevent the misuse of preservatives.

Untargeted Metabolomic Analyses of Body Fluids to Differentiate TBI DOC and NTBI DOC.

OBJECTIVE: To investigate the metabolomic differences between Traumatic brain injury (TBI) disorder of consciousness (DOC) patients and non-traumatic brain injury (NTBI) DOC patients by using cerebrospinal fluid (CSF), serum and urine samples beneficial to understand the pathological mechanism differences between the two etiologies, provide potential clues for the subsequent treatment and prognosis, and investigate the metabolome differences and similarities between TBI and NTBI among three different body fluids. METHODS: In total, 24 TBI DOC subjects and 29 NTBI DOC subjects were enrolled. CSF, serum and urine samples from TBI DOC and NTBI DOC patients were collected and analyzed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarkers and altered metabolic functions. RESULTS: When comparing TBI DOC and NTBI DOC, 36, 31 and 52 differential metabolites were obtained in CSF, serum and urine, respectively. The functional analysis of differential metabolites obtained in CSF, serum and urine were all related to amino acid metabolism. Except for amino acid metabolism, metabolic biomarkers in CSF, serum and urine mainly focus on central function, cognitive function, necrosis and apoptosis and neurological function, respectively. In CSF, the highest AUC was 0.864 (Isoproturon) and 0.816 (Proline betaine). Then, the AUC of NFurfurylformamide in serum was 0.941, while the AUC of Dihydronepetalactone and Doxepin N-oxide glucuronide were 1.0 in urine. CONCLUSION: CSF, serum and urine metabolomic analyses could differentiate TBI DOC from NTBI DOC and functional analyses showed a metabolic change difference between TBI DOC and NTBI DOC.

Oxidative stress contributes to flumioxazin-induced cardiotoxicity in zebrafish embryos.

Flumioxazin is a widely applied herbicide for the control of broadleaf weeds, including aquatic plants. Current evidence suggests that flumioxazin could induce cardiac defects (ventricular septal defects) in vertebrates, but the underlining mechanisms remain unclear. Because of the inhibitory effect of flumioxazin on polyphenol oxidase, the assumption is made that flumioxazin-induced cardiotoxicity is caused by oxidative stress. To verify whether oxidative stress plays an important role in flumioxazin-induced cardiotoxicity, we compared the differences in heart phenotype, oxidative stress level, apoptosis, and gene expression between flumioxazin exposure and a normal environment, and we also tested whether cardiotoxicity could be rescued with astaxanthin. The results showed that flumioxazin induced both cardiac malformations and the abnormal gene expression associated with cardiac development. Cardiac malformations included pericardial edema, cardiac linearization, elongated heart, cardiomegaly, cardiac wall hypocellularity, myocardial cell atrophy with a granular appearance, and a significant gap between the myocardial intima and the adventitia. An increase in oxidative stress and apoptosis was observed in the cardiac region of zebrafish after exposure to flumioxazin. The antioxidant astaxanthin reversed the cardiac malformations, excessive production of reactive oxygen species (ROS), and expression of genes for cardiac developmental and apoptosis regulation induced by flumioxazin. In addition, flumioxazin also activated aryl hydrocarbon receptor (AhR) signaling pathway genes (aryl hydrocarbon receptor 2 [ahr2], cytochrome p450 family subfamily a [cyp1a1], and b [cyp1b1]) and increased the concentration of porphyrins. The results suggest that excessive ROS production, which could be mediated through AhR, led to apoptosis, contributing to the cardiotoxicity of flumioxazin in zebrafish embryos. Environ Toxicol Chem 2023;42:2737-2746. © 2023 SETAC.

Cytological DNA methylation for cervical cancer screening: a validation set.

Background: In a previous training set with a case-controlled design, cutoff values for host EPB41L3 and JAM3 gene methylation were obtained for the detection of cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+). This validation trial was conducted to evaluate the role of DNA methylation in screening for CIN2+ by cervical cytology among unselected participants. Methods: From June 1, 2019, to September 1, 2019, in our study center, we collected liquid-based samples from cervical swabs for methylation assays and hrHPV testing in eligible patients. The primary endpoint was the diagnostic accuracy of DNA methylation and hrHPV genotyping for CIN2+ according to confirmed histology results. Results: Among 307 participants, compared with hrHPV testing, the methylation assay for CIN2+ had lower sensitivity (68.7% versus 86.1%, p=0.002) but higher specificity (96.7% versus 0.696, p<0.001). The methylation assay also had favorable sensitivity and specificity in patients with negative hrHPV testing (56.3% and 96.9%) and in patients with cervical adenocarcinoma (73.7% and 92.7%). DNA methylation had higher specificity than the hrHPV assay (100.0% versus 44.4%, p<0.001) for identifying residual CIN2+ in patients without residual lesions. Positive cervical DNA methylation was associated with a diagnostic probability of endometrial carcinoma (odds ratio 15.5 [95% confidence interval 4.1-58.6]) but not of ovarian epithelial carcinoma (1.4 [0.3-6.5]). Conclusions: The host EPB41L3 and JAM3 gene methylation assay in cervical cytology had favorable diagnostic accuracy for CIN2+ and was highly specific for residual CIN2+ lesions The methylation assay is a promising triage tool in hrHPV+ women, or even an independent tool for cervical cancer screening. The methylation status in cervical cytology could also serve as a prognostic biomarker. Its role in detecting endometrial carcinomas is worthy of further exploration.

The Triaging Effect of the Human Papillomavirus 16/18 E7 Oncoprotein Assay in HPV 16/18-Positive Patients for High-Grade Cervical Intraepithelial Neoplasia Screening: A Cross-Sectional Study.

Objective: To investigate the triaging efficacy of the human papillomavirus (HPV) 16/18 E7 oncoprotein assay for high-grade cervical intraepithelial neoplasia (CIN2+) screening in HPV 16/18-positive patients in a tertiary hospital in China. Methods: We collected 476 cervical cell samples from women who tested positive for HPV 16/18 in the gynecological clinic of Peking Union Medical College Hospital between September 2018 and September 2022 and analyzed them by the HPV 16/18 E7 oncoprotein assay before colposcopy and biopsy. The study assessed the triaging efficacy of the HPV 16/18 E7 oncoprotein assay in HPV 16/18-positive patients by analyzing its performance against the gold standard of histologically confirmed CIN2+. Results: The positive rate of the HPV 16/18 E7 oncoprotein assay was 41.0% (114/278) in the negative for intraepithelial lesions and malignancy/CIN1 group and 80.3% (159/198) in the CIN2+ group. For triage of women with a positive HPV 16/18 test for CIN2+ detection, the HPV 16/18 E7 oncoprotein assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 80.3%, 59.4%, 58.5%, and 80.9%, respectively. Furthermore, longitudinal follow-up of five patients showed a good correlation between the expression of the HPV 16/18 E7 oncoprotein and cervical lesion grades. Conclusions: As a triage method for HPV 16/18-positive patients, the HPV 16/18 E7 oncoprotein assay improves the specificity, reduces the colposcopy referral rate, and has the potential for long-term monitoring of high-grade CIN.

Alterations in factors associated with diabetic retinopathy combined with thrombosis: A review.

Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes mellitus, the incidence of which has been increasing annually, and it is the main cause of vision loss in diabetic patients and a common cause of blindness. It is now found that thrombosis plays a crucial role in the disease progression in DR patients, and the final vision loss in DR may be related to the occurrence of thrombosis in the retinal vessels, which is dominated by abnormal endothelial cell function, together with platelet dysfunction, imbalance of coagulation and fibrinolytic function, and related alterations of inflammatory factors leading to the main cause of thrombotic disease in DR patients. In this review, we examine the role between DR and thrombosis and the association of each factor, including endothelial dysfunction; platelet dysfunction; coagulation-fibrinolytic imbalance; and alterations in inflammatory factors.

Developmental and cardiac toxicity assessment of Ethyl 3-(N-butylacetamido) propanoate (EBAAP) in zebrafish embryos.

Ethyl 3-(N-butylacetamido) propanoate (EBAAP) is one of the most widely used mosquito repellents worldwide, and is also commonly used to produce cosmetics. Residues have recently been detected in surface and groundwater in many countries, and their potential to harm the environment is unknown. Therefore, more studies are needed to fully assess the toxicity of EBAAP. This is the first investigation into the developmental toxicity and cardiotoxicity of EBAAP on zebrafish embryos. EBAAP was toxic to zebrafish, with a lethal concentration 50 (LC50) of 140 mg/L at 72 hours post fertilization (hpf). EBAAP exposure also reduced body length, slowed the yolk absorption rate, induced spinal curvature and pericardial edema, decreased heart rate, promoted linear lengthening of the heart, and diminished cardiac pumping ability. The expression of heart developmental-related genes (nkx2.5, myh6, tbx5a, vmhc, gata4, tbx2b) was dysregulated, intracellular oxidative stress increased significantly, the activities of catalase (CAT) and superoxide dismutase (SOD) decreased, and malondialdehyde (MDA) content increased significantly. The expression of apoptosis-related genes (bax/bcl2, p53, caspase9, caspase3) was significantly upregulated. In conclusion, EBAAP induced abnormal morphology and heart defects during the early stages of zebrafish embryo development by potentially inducing the generation and accumulation of reactive oxygen species (ROS) in vivo and activating the oxidative stress response. These events dysregulate the expression of several genes and activate endogenous apoptosis pathways, eventually leading to developmental disorders and heart defects.

Metaproteomics Characterizes the Human Gingival Crevicular Fluid Microbiome Function in Periodontitis.

Periodontitis is the leading cause of tooth loss in adults worldwide. The human proteome and metaproteome characterization of periodontitis is not clearly understood. Gingival crevicular fluid samples were collected from eight periodontitis and eight healthy subjects. Both the human and microbial proteins were characterized by liquid chromatography coupled with high-resolution mass spectrometry. A total of 570 human proteins were found differentially expressed, which were primarily associated with inflammatory response, cell death, cellular junction, and fatty acid metabolism. For the metaproteome, 51 genera were identified, and 10 genera were found highly expressed in periodontitis, while 11 genera were downregulated. The analysis showed that microbial proteins related to butyrate metabolism were upregulated in periodontitis cases. In particular, correlation analysis showed that the expression of host proteins related to inflammatory response, cell death, cellular junction, and lipid metabolism correlates with the alteration of metaproteins, which reflect the changes of molecular function during the occurrence of periodontitis. This study showed that the gingival crevicular fluid human proteome and metaproteome could reflect the characteristics of periodontitis. This might benefit the understanding of the periodontitis mechanism.

Difference in total N and its aggregate-associated N following cropland restoration in a karst region, Southwest China.

Cropland conversion has been cited as one of the most effective measures for increasing soil nitrogen pool in karst degraded regions. However, it is still unclear how N associated with aggregate patterns and their contribution to net soil N accumulation after cropland conversion. The experiment included four treatments with one control and three restoration strategies, that is, maize-soybean rotation cultivation (the control), sugarcane, mulberry, and forage grass cultivation. Soil samples were selected to determine the soil aggregate amount and its associated N content and stock across 0-30 cm soil layer. Macro-aggregate (> 2 mm) was the predominant aggregate fraction in all cropland use types and had the largest N stock. Forage grass cultivation substantially increased N stocks in bulk soil and aggregate fractions. The N contents and stocks associated with aggregate were shown to be positively correlated with bulk soil N stocks. Furthermore, the increase in N stock in forage grass soil was largely caused by an increase in N stock within macro-aggregates (> 2 mm), which is further attributed to the increased N content within macro-aggregates. Overall, forage grass cultivation replaced maize-soybean cultivation which was proposed as an ecological restoration model to improve soil N sequestration capacity due to its function in increasing the N stock of aggregate in the karst degraded region of Southwest China.

Dynamics of aggregate-associated organic carbon after long-term cropland conversion in a karst region, southwest China.

Cropland conversion has a major impact on soil C sequestration. However, it remains unclear about the changes in soil aggregate and their contribution to C accumulation following cropland conversion in a karst region, southwest China. In this study, three different cropland use types (sugarcane, mulberry and forage grass cultivation) were selected to replace maize-soybean cultivation. The soil was collected at a depth of 0 to 30 cm for analysis of soil aggregates and their OC content. Results showed that macro-aggregate was the predominant component underlying four cropland use types. Forage grass cultivation remarkably increased the OC stock and aggregate stability (MWD and GMD). OC content and stock associated with aggregate varied with cropland use types and soil depth, but were typically highest in forage grass fields. Macro-aggregates contained higher OC content and stock than other aggregate fractions, along with soil depth underlying four cropland use types. The increases in OC stock in forage grass field was mainly due to increased OC stocks within macro-aggregates, which is further attributed to the increase in OC content within macro-aggregates. Overall, forage grass cultivation replaced maize-soybean cultivation was suggested as an ecological restoration model to enhance soil C sequestration potential, owing to its role in increasing OC stock of aggregation and aggregate stability, in the karst region of southwest China.

Benomyl-induced development and cardiac toxicity in zebrafish embryos.

Benomyl is a highly effective broad-spectrum fungicide widely used worldwide to control vegetable, fruit, and oil crop diseases. However, the mechanism of its toxicity to aquatic organisms and humans remains unknown. In this study, zebrafish were used to determine the toxicity of benomyl. It was found to be highly toxic, with a 72-h post-fertilization (hpf) lethal concentration 50 (LC50) of 1.454 mg/L. Benomyl induced severe developmental toxicity, including shorter body length, slower heart rate, and a reduced yolk absorption rate. Benomyl also increased oxidative stress in zebrafish, especially in the heart and head, as well as increasing malondialdehyde (MDA) content and decreasing catalase (CAT) and superoxide dismutase (SOD) activities. This indicates that benomyl induced reactive oxygen species (ROS) production and cell membrane peroxidation in vivo. Acridine orange (AO) staining and apoptosis factor detection further indicated that benomyl induced apoptosis in zebrafish. Overall, these findings demonstrate that benomyl disrupts cellular homeostasis by activating oxidative stress in zebrafish, resulting in an imbalance of cardiac development-related gene expression and apoptosis, which causes severe developmental toxicity and cardiac dysfunction. This study evaluated the in vivo toxicity of benomyl, which is a potential threat to aquatic organisms and humans. Possible toxicity mechanisms are explored, providing a valuable reference for the safe use of benomyl.

Alterations in soil microbial phospholipid fatty acid profile with soil depth following cropland conversion in karst region, southwest China.

The soil microbial community is a key indicator used to evaluate the effectiveness of land use changes in degraded ecosystems. However, there is currently limited information on the vertical variations of soil microbial communities under different cropland types in the karst region of southwest China. In this study, three different cropland types (sugarcane, mulberry, and forage grass) were selected to replace maize-soybean cultivation in a karst area of southwest China. Secondary forest was included for comparison. Soil was collected at soil depths of 0-10 cm, 10-20 cm, 20-30 cm, and 30-50 cm to conduct a phospholipid fatty acid (PLFA) analysis of the soil microbial communities. The results showed that the abundances of total PLFAs and PLFAs of bacteria, fungi, actinomycetes, and arbuscular mycorrhizal fungi were significantly higher in forage grass cultivation and secondary forest areas than those in other three cropland types. The abundance of total PLFA and its functional groups significantly decreased with increasing soil depth. Bacteria was the predominant community (> 52%) across all land use types and soil depths. A principal component analysis indicated that soil microbial PLFA composition in forage grass field and secondary forest areas differed significantly from that in mulberry, sugarcane, and maize-soybean fields across 0-50-cm soil layer. Soil organic carbon was identified as the primary factor affecting the abundance and structure of soil microbial communities in the four soil layers. These results suggest that greater improvements in soil quality and fertility could be made by replacing the maize-soybean rotation system with forage grass cultivation than by replacing it with mulberry or sugarcane cultivation in the karst region of southwest China.

Neutrophils: As a Key Bridge between Inflammation and Thrombosis.

Immunothrombosis is a mechanism of defense of the organism against pathogenic microorganisms that increases their recognition, limitation, and clearance and is part of the innate immune defense. Physiological immunothrombosis is beneficial to the body against the invasion of pathogenic microorganisms, but when immunothrombosis is out of control, it is easy to cause thrombotic diseases, thus, causing unpredictable consequences to the body. Neutrophils play a pivotal role in this process. Understanding the mechanism of neutrophils in immune thrombosis and out-of-control is particularly important for the treatment of related thrombotic diseases. In this review, we studied the role of neutrophils in immune thrombosis and each link out of control (including endothelial cell dysfunction; activation of platelets; activation of coagulation factor; inhibition of the anticoagulation system; and inhibition of the fibrinolysis system).

Effects of Long-Term Fertilizer Practices on Rhizosphere Soil Autotrophic CO2-Fixing Bacteria under Double Rice Ecosystem in Southern China.

Soil autotrophic bacterial communities play a significant role in the soil carbon (C) cycle in paddy fields, but little is known about how rhizosphere soil microorganisms respond to different long-term (35 years) fertilization practices under double rice cropping ecosystems in southern China. Here, we investigated the variation characteristics of rhizosphere soil RubisCO gene cbbL in the double rice ecosystems of in southern China where such fertilization practices are used. For this experiment we set up the following fertilizer regime: without any fertilizer input as a control (CK), inorganic fertilizer (MF), straw returning (RF), and organic and inorganic fertilizer (OM). We found that abundances of cbbL, 16S rRNA genes and RubisCO activity in rhizosphere soil with OM, RF and MF treatments were significantly higher than that of CK treatment. The abundances of cbbL and 16S rRNA genes in rhizosphere soil with OM treatment were 5.46 and 3.64 times higher than that of CK treatment, respectively. Rhizosphere soil RubisCO activity with OM and RF treatments increased by 50.56 and 45.22%, compared to CK treatment. Shannon and Chao1 indices for rhizosphere soil cbbL libraries with RF and OM treatments increased by 44.28, 28.56, 29.60, and 23.13% compared to CK treatment. Rhizosphere soil cbbL sequences with MF, RF and OM treatments mainly belonged to Variovorax paradoxus, uncultured proteobacterium, Ralstonia pickettii, Thermononospora curvata, and Azoarcus sp.KH33C. Meanwhile, cbbL-carrying bacterial composition was obviously influenced by soil bulk density, rhizosphere soil dissolved organic C, soil organic C, and microbial biomass C contents. Fertilizer practices were the principal factor influencing rhizosphere soil cbbL-carrying bacterial communities. These results showed that rhizosphere soil autotrophic bacterial communities were significantly changed under conditions of different long-term fertilization practices Therefore, increasing rhizosphere soil autotrophic bacteria community with crop residue and organic manure practices was found to be beneficial for management of double rice ecosystems in southern China.

[Effects of different long-term fertilization patterns on net carbon sink effect and economic benefits in double cropping rice paddy ecosystem in southern China]. / 长期不同施肥模式对南方双季稻田生态系统净碳汇效应和经济收益的影响.

There is close relationship between fertilizer managements and net carbon (C) sink effect, economic benefits in rice paddy ecosystem. Based on a long-term (35-year) field experiment, we analyzed the effects of different fertilization patterns on soil C sequestration rate, C density of topsoil, annual C balance, and economic benefits in the double cropping rice paddy in southern China. There were four fertilization treatments, chemical fertilizer alone (MF), rice straw and chemical fertilizer (RF), 30% organic manure and 70% chemical fertilizer (OM), and without any fertilizer input as a control (CK). The results showed that soil C pool in the double cropping rice paddy field under different fertilization treatments changed from 216.02 to 866.74 kg·hm-2·a-1, and soil C pool under OM treatment were significantly higher than that of MF, RF and CK. The soil C sequestration rates in the double cropping rice paddy field under different fertilization treatments ranged from 51.5 to 650.7 kg·hm-2·a-1, and that of C density of topsoil was from 55.64 to 78.42 t·hm-2. The order of soil C sequestration rates and C density of topsoil was OM>RF>MF>CK. The change range of C adsorption in the double cropping rice paddy field ecosystem was from 4.42 to 9.32 t C·hm-2·a-1, with an order of OM>RF>MF>CK. Compared with the MF treatment, soil net C sink under OM and RF treatments increased by 27.6% and 13.6%, respectively. The change range of C cost material input ranged from 1.49 to 2.17 t C·hm-2·a-1, and that of annual economic benefits was from 1.30×103 to 7.83×103 yuan·hm-2·a-1 with an order of RF>OM>MF>CK. The net income of economic benefits of OM, RF and MF treatments were significantly higher than that of CK. Generally, soil C sequestration rate, C sink effect and annual economic benefits were increased by the long-term application of organic manure and rice straw returning together with chemical fertilizer, which could increase soil organic carbon storage in the double cropping rice paddy field of southern China.

A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 (COVID-19). Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2 variants. Here, we found that all-trans retinoic acid (ATRA), a vitamin A (retinol) derivative, showed potent antiviral activity against all SARS-CoV-2 variants in both human cell lines and human organoids of the lower respiratory tract. Mechanistically, ATRA directly binds in a deep hydrophobic pocket of the receptor binding domain (RBD) located on the top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the "down" RBDs and locks most of the S trimers in an RBD "all-down" and ACE2-inaccessible inhibitory conformation. In summary, our results reveal the pharmacological biotargets and structural mechanism of ATRA and other retinoids in SARS-CoV-2 infection and suggest that ATRA and its derivatives could be potential hit compounds against a broad spectrum of coronaviruses. IMPORTANCE Retinoids, a group of compounds including vitamin A and its active metabolite all-trans retinoic acid (ATRA), regulate serial physiological activity in multiple organ systems, such as cell growth, differentiation, and apoptosis. The ATRA analogues reported to date include more than 4,000 natural and synthetic molecules that are structurally and/or functionally related to ATRA. Here, we found that ATRA showed potent antiviral activity against all SARS-CoV-2 variants by directly binding in a deep hydrophobic pocket of the receptor binding domain (RBD) located on top of the SARS-CoV-2 spike protein (S) trimer. The bound ATRA mediates strong interactions between the "down" RBDs and locks most of the S trimers in an RBD "all-down" and ACE2-inaccessible inhibitory conformation, suggesting the pharmacological feasibility of using ATRA or its derivatives as a remedy for and prevention of COVID-19 disease.