FGF13 enhances the function of TRPV1 by stabilizing microtubules and regulates acute and chronic itch.

Itching is an aversive somatosensation that triggers the desire to scratch. Transient receptor potential (TRP) channel proteins are key players in acute and chronic itch. However, whether the modulatory effect of fibroblast growth factor 13 (FGF13) on acute and chronic itch is associated with TRP channel proteins is unclear. Here, we demonstrated that conditional knockout of Fgf13 in dorsal root ganglion neurons induced significant impairment in scratching behaviors in response to acute histamine-dependent and chronic dry skin itch models. Furthermore, FGF13 selectively regulated the function of the TRPV1, but not the TRPA1 channel on Ca2+ imaging and electrophysiological recordings, as demonstrated by a significant reduction in neuronal excitability and current density induced by TRPV1 channel activation, whereas TRPA1 channel activation had no effect. Changes in channel currents were also verified in HEK cell lines. Subsequently, we observed that selective modulation of TRPV1 by FGF13 required its microtubule-stabilizing effect. Furthermore, in FGF13 knockout mice, only the overexpression of FGF13 with a tubulin-binding domain could rescue TRP channel function and the impaired itch behavior. Our findings reveal a novel mechanism by which FGF13 is involved in TRPV1-dependent itch transduction and provide valuable clues for alleviating pathological itch syndrome.

Management-induced changes in soil organic carbon and related crop yield dynamics in China's cropland.

Enhancing soil organic carbon (SOC) sequestration and food supply are vital for human survival when facing climate change. Site-specific best management practices (BMPs) are being promoted for adoption globally as solutions. However, how SOC and crop yield are related to each other in responding to BMPs remains unknown. Here, path analysis based on meta-analysis and machine learning was conducted to identify the effects and potential mechanisms of how the relationship between SOC and crop yield responds to site-specific BMPs in China. The results showed that BMPs could significantly enhance SOC and maintain or increase crop yield. The maximum benefits in SOC (30.6%) and crop yield (79.8%) occurred in mineral fertilizer combined with organic inputs (MOF). Specifically, the optimal SOC and crop yield would be achieved when the areas were arid, soil pH was ≥7.3, initial SOC content was ≤10 g kg-1 , duration was >10 years, and the nitrogen (N) input level was 100-200 kg ha-1 . Further analysis revealed that the original SOC level and crop yield change showed an inverted V-shaped structure. The association between the changes in SOC and crop yield might be linked to the positive role of the nutrient-mediated effect. The results generally suggested that improving the SOC can strongly support better crop performance. Limitations in increasing crop yield still exist due to low original SOC level, and in regions where the excessive N inputs, inappropriate tillage or organic input is inadequate and could be diminished by optimizing BMPs in harmony with site-specific conditions.

Two-dimensional displacement estimation of one-dimensional laser speckle images for detection of acoustic vibration.

Detection and recovery of audio signals using optical methods is an appealing topic. Observing the movement of secondary speckle patterns is a convenient method for such a purpose. In order to have less computational cost and faster processing, one-dimensional laser speckle images are captured by an imaging device, while it sacrifices the ability to detect speckle movement along one axis. This paper proposes a laser microphone system to estimate the two-dimensional displacement from one-dimensional laser speckle images. Hence, we can regenerate audio signals in real time even as the sound source is rotating. Experimental results show that our system is capable of reconstructing audio signals under complex conditions.

Changes in cropland soil carbon through improved management practices in China: A meta-analysis.

Recommended management practices (RMPs, e.g., manuring, no-tillage, crop residue return) can increase soil organic carbon (SOC), reduce greenhouse gas emissions, and maintain soil health in croplands. However, there is no consensus on how RMPs affect the SOC storage potential of cropland soils for climate change mitigation. Here, based on 2301 comparisons from 158 peer-reviewed papers, a meta-analysis was conducted to explore management-induced SOC stock changes and their variations under different conditions. The results show that SOC stocks in the 0-20 cm layer were increased by 31.8% when chemical fertilization combined with manure application was compared with no fertilizer; 9.98% when no-tillage was compared with plow tillage; and 10.84% when straw return was compared with removal. The RMPs favorably increased SOC stock in arid areas, and in alkaline and fine-textured soils. Initial SOC, carbon-nitrogen ratio, and experimental duration could also affect SOC storage. Compared with the initial SOC stock, RMPs increased the SOC sequestration potential by 2.6-4.5% in the 0-20 cm soil depth, indicating that these practices can help China achieve targets to increase SOC by 4.0‰. Hence, it is essential to implement RMPs for climate change mitigation and soil fertility improvement.

Responses of soil pH to no-till and the factors affecting it: A global meta-analysis.

No-till (NT) is a sustainable option because of its benefits in controlling erosion, saving labor, and mitigating climate change. However, a comprehensive assessment of soil pH response to NT is still lacking. Thus, a global meta-analysis was conducted to determine the effects of NT on soil pH and to identify the influential factors and possible consequences based on the analysis of 114 publications. When comparing tillage practices, the results indicated an overall significant decrease by 1.33 ± 0.28% in soil pH under NT than that under conventional tillage (p < .05). Soil texture, NT duration, mean annual temperature (MAT), and initial soil pH are the critical factors affecting soil pH under NT. Specifically, with significant variations among subgroups, when compared to conventional tillage, the soil under NT had lower relative changes in soil pH observed on clay loam soil (-2.44%), long-term implementation (-2.11% for more than 15 years), medium MAT (-1.87% in the range of 8-16℃), neutral soil pH (-2.28% for 6.5 < initial soil pH < 7.5), mean annual precipitation (-1.95% in the range of 600-1200 mm), in topsoil layers (-2.03% for 0-20 cm), with crop rotation (-1.98%), N fertilizer input (the same for NT and conventional tillage) of 100-200 kg N ha-1 (-1.83%), or crop residue retention (-1.52%). Changes in organic matter decomposition under undisturbed soil and with crop residue retention might lead to a higher concentration of H+ and lower of basic cations (i.e., calcium, magnesium, and potassium), which decrease the soil pH, and consequently, impact nutrient dynamics (i.e., soil phosphorus) in the surface layer under NT. Furthermore, soil acidification may be aggravated by NT within site-specific conditions and improper fertilizer and crop residue management and consequently leading to adverse effects on soil nutrient availability. Thus, there is a need to identify strategies to ameliorate soil acidification under NT to minimize the adverse consequences.

Mechanisms of soil organic carbon stability and its response to no-till: A global synthesis and perspective.

Mechanisms of soil organic carbon (SOC) stabilization have been widely studied due to their relevance in the global carbon cycle. No-till (NT) has been frequently adopted to sequester SOC; however, limited information is available regarding whether sequestered SOC will be stabilized for long term. Thus, we reviewed the mechanisms affecting SOC stability in NT systems, including the priming effects (PE), molecular structure of SOC, aggregate protection, association with soil minerals, microbial properties, and environmental effects. Although a more steady-state molecular structure of SOC is observed in NT compared with conventional tillage (CT), SOC stability may depend more on physical and chemical protection. On average, NT improves macro-aggregation by 32.7%, and lowers SOC mineralization in macro-aggregates compared with CT. Chemical protection is also important due to the direct adsorption of organic molecules and the enhancement of aggregation by soil minerals. Higher microbial activity in NT could also produce binding agents to promote aggregation and the formation of metal-oxidant organic complexes. Thus, microbial residues could be stabilized in soils over the long term through their attachment to mineral surfaces and entrapment of aggregates under NT. On average, NT reduces SOC mineralization by 18.8% and PE intensities after fresh carbon inputs by 21.0% compared with CT (p < .05). Although higher temperature sensitivity (Q10 ) is observed in NT due to greater Q10 in macro-aggregates, an increase of soil moisture regime in NT could potentially constrain the improvement of Q10 . This review improves process-based understanding of the physical and chemical mechanism of protection that can act, independently or interactively, to enhance SOC preservation. It is concluded that SOC sequestered in NT systems is likely to be stabilized over the long term.

Responses of greenhouse gas emissions to residue returning in China's croplands and influential factors: A meta-analysis.

Climate change is a global issue threatening agricultural production and human survival. However, agriculture sector is a major source of global greenhouse gases (GHGs), especially CH4 and N2O. Crop residue returning (RR) is an efficient practice to sequestrate soil carbon and increase crop yields. However, the efficiency of RR to mitigate climate change and maintain food security will be affected by the response of GHG emissions at both per area-scale and per yield-scale. Therefore, a national meta-analysis was conducted using 309 comparisons from 44 publications to assess the responses of GHG emissions to RR in China's croplands. The results indicated that little response of GWP to RR was observed with conditions under lower nitrogen fertilizer input rates (0-120 kg ha-1), mulch retention, returning one time in double cropping systems, returning with half residue, weakly acidic soil (pH 5.5-6.5), initial SOC contents >20 g kg-1, or mean annual precipitation <1000 mm. In order to mitigate climate change and sustain food security, RR combined with paddy-upland rotation, nitrogen fertilizer input rates of 240-360 kg ha-1, and neutral soil (pH 6.5-7.5) could decrease GWP at per unit of crop yield, which ultimately leads to a lower effect on GHGI and a higher crop production efficiency. In-depth studies should be conducted in the future to explore the interactions between various factors influencing GHG emissions under RR conditions. Overall, optimizing the interactions with management and site-specific conditions, potential for regulating GHGs emissions of RR can be enhanced.

Effects of tillage management on soil carbon decomposition and its relationship with soil chemistry properties in rice paddy fields.

Decreasing the soil organic carbon (SOC) decomposition is critical to improve the quality of the soil and mitigate atmospheric CO2 emissions. To improve the ability to protect the SOC by optimizing tillage management, this study investigated the laboratory-based SOC mineralization (decomposition) and soil chemical properties under different tillage practices, including no tillage with straw mulch (NTS), rotary tillage with straw incorporated (RTS), moldboard plow tillage with straw incorporated (CTS) and moldboard plow tillage with straw removal (CT). Soil samples of six sampling dates from April 2017 to October 2018 were incubated at 25 °C and 70% water holding capacity for 60 d. Repeated Variance Analyses were conducted to compare the means of different treatments. The results showed that the average cumulative SOC mineralization (Cm) at the 0-5 cm soil depth was 7.09 g CO2 kg-1 soil under NTS, which was higher (P < 0.05) than that of the other treatments. However, the C mineralizability at both the 0-5 and 5-10 cm soil depths were lower (P < 0.05) under the NTS (0.16 and 0.15 g CO2 g-1 SOC) compared with the CTS and CT. Non-microbial CO2 emissions (CO2 emissions in sterilized soil) contributed to the lower C mineralizability under NTS, due to the lower mineralizability (0.041-0.089 g CO2 g-1 SOC) of sterilized soil under this treatment. Furthermore, some of the abiotic factors (e.g., C/N ratio and SOC content) significantly correlated with the Cm and C mineralizability. These factors might be critical for the ability to protect SOC under NTS. In summary, conservation tillage is an optimal management due to its protection on SOC, and part of this protection appeared to have been contributed by the soil abiotic factors, which were formed by long-term tillage management.

[Discussions on Clinical Characteristics and Diagnostic Criteria of Pertussis in Children].

OBJECTIVE: To compare the clinical manifestations of pertussis in children of different ages and different immunization statuses in Wenzhou, and to explore the limitations of diagnostic criteria for pertussis. METHODS: The clinical data of 288 children diagnosed with pertussis at Yuying Children's Hospital & the Second Affiliated Hospital of Wenzhou Medical University from October 2017 to December 2019 were retrospectively analyzed. The clinical characteristics of children of different ages and different immunization statuses were analyzed. Their clinical data were compared to relevant diagnostic criteria of pertussis in children of different ages according to the Recommendations for Diagnosis and Treatment of Chinese Children with Pertussis and the diagnosis conformity rate was analyzed. RESULTS: Among the 288 children, 124 cases (43.06%) were 3 months old or younger, and 164 cases (288, 56.94%) were >3 months old. Among patients≤3 months of age, cyanosis, three-depression sign, face redness, dyspnea and peripheral blood lymphocyte ratio were significantly higher than those of patients >3 months of age. They also had higher incidence of pneumonia, higher proportion of developing severe pertussis, and longer stay at the hospital. All these findings showed statistically significant difference ( P<0.05). 83 children were fully immunized (receiving the full course of vaccination), and 205 were not fully immunized (not receiving the full course of vaccination or being unvaccinated). The proportion of children presenting cyanosis, shortness of breath, three depression sign and face redness in the incomplete immunization group was higher than that in the complete immunization group. In the incomplete immunization group, the proportion of lymphocytes was higher, the level of C-reactive protein (CRP) was lower, and the length of hospitalization was longer than those of the complete immunization group. All the differences were statistically significant ( P<0.05). Among patients aged ≤3 months, the conformity rate of diagnosis (112/114, 90.32%) upon admission was higher than that among patients aged >3 months (119/164, 72.56%). Among patients aged ≤3 months, 41.94% (52/124, while 54.03% (67/124) of the patients aged ≤3 months had WBC count <20×10 9 L -1. CONCLUSION: Pertussis in children ≤3 months of age in Wenzhou City were more serious, showing higher rate of diagnosis conforming to the recommended clinical diagnostic criteria than that in children >3 months old. The WBC threshold in routine blood test of ≤3 months old could be lowered appropriately and the current diagnostic criteria still needed improvement.

Dynamics in soil organic carbon of wheat-maize dominant cropping system in the North China Plain under tillage and residue management.

A site experiment was conducted to assess temporal dynamics of soil organic carbon (SOC) and the drivers under no-tillage (NT) and residue retention (RR) in the North China Plain (NCP). The results indicated that NT and RR can significantly increase SOC up to a depth of 30 cm. On average, NT increased SOC by 8.1-34.5% compared with PT, and RR increased SOC by 3.5-14.4% compared with R0 at 0-10 cm. Increases in SOC under NT or RR could be increased by 4-10 percentage points through the significantly positive interactions of NT and RR. Among the sources of SOC variations, tillage-induced variations accounted for 74.4 and 44.3% of the total variations in SOC at 0-5 cm for wheat and maize season, respectively. Experimental duration was also a significant source of variation. Stepwise regression indicated dynamics in SOC at 0-5 cm mainly due to the positive effects of precipitation, the negative effects of soil bulk density for the wheat season, the negative effects of radiation for the maize season, and antagonistic effects of temperature between wheat and maize season. Generally, positive effects of NT and RR on SOC were both confirmed, but fluctuations and variations induced by interactions of practices and seasonal climatic conditions were also significant in the NCP.

MicroRNA-21 antisense oligonucleotide improves the sensitivity of A375 human melanoma cell to Cisplatin: An in vitro study.

This study explored Cisplatin resistance effect of microRNA-21 (miR-21) antisense oligonucleotide (AS-ODN) in human melanoma A375 cell. AS-ODN was transfected in melanoma A375 cells and Cisplatin-resistant cell line A375/CDDP, and divided into the AS-ODN, nonsense oligonucleotide (NS-ODN) and normal groups. Cell ultrastructure changes were observed through transmission electron microscope. MiR-21 AS-ODN could be tested cell growth effect in different time periods by trypan blue exclusion. MiR-21 mRNA expression change was detected by quantitative fluorescence PCR. Cell apoptosis, cycle distribution and miR-21 AS-ODN effect on proliferation and Cisplatin sensitivity were tested by flow cytometry, MTT assay, TUNEL, and Clonogenic assay. Cell apoptosis was observed after transfection 24 h with the AS-ODN group, while the NS-ODN and normal group cells had no apoptotic symptoms; Compared with the normal group, the AS-ODN group began to show obvious cell growth inhibition effect after transfection 24 h lasting 72 h (all P < 0.05), but the NS-ODN group had no significant difference (P > 0.05). miR-21 mRNA expression in the AS-ODN group was obviously decreased with rising apoptosis rate (all P < 0.05) and there was no significant difference in the NS-ODN group (P > 0.05). MiR-21 AS-ODN could remarkably increase A375 cell and A375/CDDP cell sensitivity to Cisplatin (P < 0.05), while A375 cell sensitivity to Cisplatin between the NS-ODN group and the normal group had no difference. MiR-21 AS-ODN decreased IC50 and increased Cisplatin sensitivity for A375 cells and A375/CDDP cells, which would be a new target of melanoma treatment.

Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory.

The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM) test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1ß in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function.

Bats host diverse parvoviruses as possible origin of mammalian dependoparvoviruses and source for bat-swine interspecies transmission.

Compared to the enormous species diversity of bats, relatively few parvoviruses have been reported. We detected diverse and potentially novel parvoviruses from bats in Hong Kong and mainland China. Parvoviruses belonging to Amdoparvovirus, Bocaparvovirus and Dependoparvovirus were detected in alimentary, liver and spleen samples from 16 different chiropteran species of five families by PCR. Phylogenetic analysis of partial helicase sequences showed that they potentially belonged to 25 bocaparvovirus, three dependoparvovirus and one amdoparvovirus species. Nearly complete genome sequencing confirmed the existence of at least four novel bat bocaparvovirus species (Rp-BtBoV1 and Rp-BtBoV2 from Rhinolophus pusillus, Rs-BtBoV2 from Rhinolophus sinicus and Rol-BtBoV1 from Rousettus leschenaultii) and two novel bat dependoparvovirus species (Rp-BtAAV1 from Rhinolophus pusillus and Rs-BtAAV1 from Rhinolophus sinicus). Rs-BtBoV2 was closely related to Ungulate bocaparvovirus 5 with 93, 72.1 and 78.7 % amino acid identities in the NS1, NP1 and VP1/VP2 genes, respectively. The detection of bat bocaparvoviruses, including Rs-BtBoV2, closely related to porcine bocaparvoviruses, suggests recent interspecies transmission of bocaparvoviruses between bats and swine. Moreover, Rp-BtAAV1 and Rs-BtAAV1 were most closely related to human AAV1 with 48.7 and 57.5 % amino acid identities in the rep gene. The phylogenetic relationship between BtAAVs and other mammalian AAVs suggests bats as the ancestral origin of mammalian AAVs. Furthermore, parvoviruses of the same species were detected from multiple bat species or families, supporting the ability of bat parvoviruses to cross species barriers. The results extend our knowledge on the diversity of bat parvoviruses and the role of bats in parvovirus evolution and emergence in humans and animals.

Epidemiological and molecular characteristics of emergent dengue virus in Yunnan Province near the China-Myanmar-Laos border, 2013-2015.

BACKGROUND: Yunnan Province is located in southwestern China and neighbors the Southeast Asian countries, all of which are dengue-endemic areas. In 2000-2013, sporadic imported cases of dengue fever (DF) were reported almost annually in Yunnan Province. During 2013-2015, we confirmed that a large-scale indigenous DF outbreak emerged in cities of Yunnan Province near the China-Myanmar-Laos border. METHODS: Epidemiological characteristics of DF in Yunnan Province during 2013-2015 were evaluated by retrospective analysis. A total of 232 dengue virus (DENV)-positive sera were randomly collected for sequence analysis of the capsid/premembrane region of DENV from patients with DF in Yunnan Province. The envelope gene of DENV isolates was also amplified and sequenced. Phylogenetic analyses were performed using the neighbor-joining method with the Tajima-Nei model. RESULTS: Phylogenetically, all DENV-positive samples could be classified into DENV-1 genotype I and DENV-2 Asian I genotype during 2013-2015 and DENV-4 genotype I in 2015 from Ruili City; and DENV-3 genotype II in 2013 and DENV-2 Cosmopolitan genotype in 2015 from Xishuangbanna Prefecture. CONCLUSIONS: Our results indicated that imported DF from patients from Laos and Myanmar was the primary cause of the DF epidemic in Yunnan Province. Additionally, DENV strains of all four serotypes were identified in indigenous cases in Yunnan Province during the same time period, while the dengue epidemic pattern observed in southwestern Yunnan showed characteristics of a hypoendemic nature: circulation of DENV-1 and DENV-2 over consecutive years.

Antibiotics for treatment of acute exacerbation of chronic obstructive pulmonary disease: a network meta-analysis.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most common reason for the hospitalization and death of pulmonary patients. The use of antibiotics as adjuvant therapy for AECOPD, however, is still a matter of debate. METHODS: In this study, we searched the PubMed, EmBase, and Cochrane databases for randomized controlled trials published until September 2016 that evaluated the use of antibiotics for AECOPD treatment. The major outcome variables were clinical cure rate and adverse effects. The microbiological response rate, relapse of exacerbation, and mortality were also analysed. A random-effect network was used to assess the effectiveness and tolerance of each antibiotic used for AECOPD treatment. RESULTS: In this meta-analysis, we included 19 articles that assessed 17 types of antibiotics used in 5906 AECOPD patients. The cluster ranking showed that dirithromycin had a high clinical cure rate with a low rate of adverse effects. Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole had high clinical cure rates with median rates of adverse effects. In terms of the microbiological response rate, only doxycycline was significantly better than placebo (odds ratio (OR), 3.84; 95% confidence interval (CI), 1.96-7.54; p < 0.001). There were no other significant results with respect to the frequency of recurrence or mortality. CONCLUSIONS: Our study indicated that dirithromycin is adequate for improving the clinical cure rate of patients with AECOPD with few adverse effects. Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole are also recommended for disease treatment. However, caution should still be exercised when using antibiotics to treat AECOPD. Trial Registration Not applicable.

Generation and characterization of a breast carcinoma model by PyMT overexpression in mammary epithelial cells of tree shrew, an animal close to primates in evolution.

The tree shrew is becoming an attractive experimental animal model for human breast cancer owing to a closer relationship to primates/humans than rodents. Tree shrews are superior to classical primates because tree shrew are easier to manipulate, maintain and propagate. It is required to establish a high-efficiency tree shrew breast cancer model for etiological research and drug assessment. Our previous studies suggest that 7,12-dimethylbenz(a)anthracene (DMBA) and medroxyprogesterone acetate (MPA) induce breast tumors in tree shrews with a low frequency (<50%) and long latency (∼ 7-month), making these methods less than ideal. We induced mammary tumors in tree shrew (Tupaia belangeri chinensis) by injection of lentivirus expressing the PyMT oncogene into mammary ducts of 22 animals. Most tree shrews developed mammary tumors with a latency of about three weeks, and by 7 weeks all injected tree shrews had developed mammary tumors. Among these, papillary carcinoma is the predominant tumor type. One case showed lymph node and lung metastasis. Interestingly, the expression levels of phosphorylated AKT, ERK and STAT3 were elevated in 41-68% of PyMT-induced mammary tumors, but not all tumors. Finally, we observed that the growth of PyMT-induced tree shrew mammary tumors was significantly inhibited by Cisplatin and Epidoxorubicin. PyMT-induced tree shrew mammary tumor model may be suitable for further breast cancer research and drug development, due to its high efficiency and short latency.

Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination.

UNLABELLED: Despite the identification of horseshoe bats as the reservoir of severe acute respiratory syndrome (SARS)-related coronaviruses (SARSr-CoVs), the origin of SARS-CoV ORF8, which contains the 29-nucleotide signature deletion among human strains, remains obscure. Although two SARS-related Rhinolophus sinicus bat CoVs (SARSr-Rs-BatCoVs) previously detected in Chinese horseshoe bats (Rhinolophus sinicus) in Yunnan, RsSHC014 and Rs3367, possessed 95% genome identities to human and civet SARSr-CoVs, their ORF8 protein exhibited only 32.2 to 33% amino acid identities to that of human/civet SARSr-CoVs. To elucidate the origin of SARS-CoV ORF8, we sampled 348 bats of various species in Yunnan, among which diverse alphacoronaviruses and betacoronaviruses, including potentially novel CoVs, were identified, with some showing potential interspecies transmission. The genomes of two betacoronaviruses, SARSr-Rf-BatCoV YNLF_31C and YNLF_34C, from greater horseshoe bats (Rhinolophus ferrumequinum), possessed 93% nucleotide identities to human/civet SARSr-CoV genomes. Although these two betacoronaviruses displayed lower similarities than SARSr-Rs-BatCoV RsSHC014 and Rs3367 in S protein to civet SARSr-CoVs, their ORF8 proteins demonstrated exceptionally high (80.4 to 81.3%) amino acid identities to that of human/civet SARSr-CoVs, compared to SARSr-BatCoVs from other horseshoe bats (23.2 to 37.3%). Potential recombination events were identified around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. The expression of ORF8 subgenomic mRNA suggested that the ORF8 protein may be functional in SARSr-Rf-BatCoVs. The high Ka/Ks ratio among human SARS-CoVs compared to that among SARSr-BatCoVs supported that ORF8 is under strong positive selection during animal-to-human transmission. Molecular clock analysis using ORF1ab showed that SARSr-Rf-BatCoV YNLF_31C and YNLF_34C diverged from civet/human SARSr-CoVs in approximately 1990. SARS-CoV ORF8 originated from SARSr-CoVs of greater horseshoe bats through recombination, which may be important for animal-to-human transmission. IMPORTANCE: Although horseshoe bats are the primary reservoir of SARS-related coronaviruses (SARSr-CoVs), it is still unclear how these bat viruses have evolved to cross the species barrier to infect civets and humans. Most human SARS-CoV epidemic strains contain a signature 29-nucleotide deletion in ORF8, compared to civet SARSr-CoVs, suggesting that ORF8 may be important for interspecies transmission. However, the origin of SARS-CoV ORF8 remains obscure. In particular, SARSr-Rs-BatCoVs from Chinese horseshoe bats (Rhinolophus sinicus) exhibited <40% amino acid identities to human/civet SARS-CoV in the ORF8 protein. We detected diverse alphacoronaviruses and betacoronaviruses among various bat species in Yunnan, China, including two SARSr-Rf-BatCoVs from greater horseshoe bats that possessed ORF8 proteins with exceptionally high amino acid identities to that of human/civet SARSr-CoVs. We demonstrated recombination events around ORF8 between SARSr-Rf-BatCoVs and SARSr-Rs-BatCoVs, leading to the generation of civet SARSr-CoVs. Our findings offer insight into the evolutionary origin of SARS-CoV ORF8 protein, which was likely acquired from SARSr-CoVs of greater horseshoe bats through recombination.

Methane and nitrous oxide emissions under no-till farming in China: a meta-analysis.

No-till (NT) practices are among promising options toward adaptation and mitigation of climate change. However, the mitigation effectiveness of NT depends not only on its carbon sequestration potential but also on soil-derived CH4 and N2O emissions. A meta-analysis was conducted, using a dataset involving 136 comparisons from 39 studies in China, to identify site-specific factors which influence CH4 emission, CH4 uptake, and N2O emission under NT. Comparative treatments involved NT without residue retention (NT0), NT with residue retention (NTR), compared to plow tillage (PT) with residue removed (PT0). Overall, NT0 significantly decreased CH4 emission by ~30% (P < 0.05) compared to PT0 with an average emission 218.8 kg ha(-1) for rice paddies. However, the increase in N2O emission could partly offset the benefits of the decrease in CH4 emission under NT compared to PT0. NTR significantly enhanced N2O emission by 82.1%, 25.5%, and 20.8% (P < 0.05) compared to PT0 for rice paddies, acid soils, and the first 5 years of the experiments, respectively. The results from categorical meta-analysis indicated that the higher N2O emission could be mitigated by adopting NT within alkaline soils, for long-term duration, and with less N fertilization input when compared to PT0. In addition, the natural log (lnR) of response ratio of CH4 and N2O emissions under NT correlated positively (enhancing emission) with climate factors (temperature and precipitation) and negatively (reducing emission) with experimental duration, suggesting that avoiding excess soil wetness and using NT for a long term could enhance the benefits of NT. Therefore, a thorough understanding of the conditions favoring greenhouse gas(es) reductions is essential to achieving climate change mitigation and advancing food security in China.

Activation of neuronal Kv7/KCNQ/M-channels by the opener QO58-lysine and its anti-nociceptive effects on inflammatory pain in rodents.

AIM: The aim of this study was to examine the activation of neuronal Kv7/KCNQ channels by a novel modified Kv7 opener QO58-lysine and to test the anti-nociceptive effects of QO58-lysine on inflammatory pain in rodent models. METHODS: Assays including whole-cell patch clamp recordings, HPLC, and in vivo pain behavioral evaluations were employed. RESULTS: QO58-lysine caused instant activation of Kv7.2/7.3 currents, and increasing the dose of QO58-lysine resulted in a dose-dependent activation of Kv7.2/Kv7.3 currents with an EC50 of 1.2±0.2 µmol/L. QO58-lysine caused a leftward shift of the voltage-dependent activation of Kv7.2/Kv7.3 to a hyperpolarized potential at V1/2=-54.4±2.5 mV from V1/2=-26.0±0.6 mV. The half-life in plasma (t1/2) was derived as 2.9, 2.7, and 3.0 h for doses of 12.5, 25, and 50 mg/kg, respectively. The absolute bioavailabilities for the three doses (12.5, 25, and 50 mg/kg) of QO58-lysine (po) were determined as 13.7%, 24.3%, and 39.3%, respectively. QO58-lysine caused a concentration-dependent reduction in the licking times during phase II pain induced by the injection of formalin into the mouse hindpaw. In the Complete Freund's adjuvant (CFA)-induced inflammatory pain model in rats, oral or intraperitoneal administration of QO58-lysine resulted in a dose-dependent increase in the paw withdrawal threshold, and the anti-nociceptive effect on mechanical allodynia could be reversed by the channel-specific blocker XE991 (3 mg/kg). CONCLUSION: Taken together, our findings show that a modified QO58 compound (QO58-lysine) can specifically activate Kv7.2/7.3/M-channels. Oral or intraperitoneal administration of QO58-lysine, which has improved bioavailability and a half-life of approximately 3 h in plasma, can reverse inflammatory pain in rodent animal models.

Obesity in children with different risk factors for obstructive sleep apnea: a community-based study.

This study investigated the association between obesity and obstructive sleep apnea (OSA) in preschool and school-age children. Parents of obese and randomly chosen normal weight children completed a questionnaire on sleep-related symptoms, demography, family, and medical history. All subjects were invited to undergo polysomnography (PSG). OSA cases were defined as obstructive apnea hypopnea index (OAHI) ≥1. A total of 5930 children were studied with 9.5% obese (11.9% boys/6.1% girls), 205/2680 preschool and 360/3250 school children. There were 1030 children (535 obese/495 normal weight) who underwent PSG. OSA was higher in obese children and obese school children had higher OAHI, arousal index, and shorter total sleep time. However, there was no positive correlation between OSA and body mass index (BMI). The main risk factors for OSA in preschool children were adenotonsillar hypertrophy and recurrent respiratory tract infection. The main cause for OSA in school children was a history of parental snoring and obesity. Mallampati scores and sleep-related symptoms were found to be associated with OSA in both preschool and school children. CONCLUSION: We demonstrated differential risk factors for OSA in obese children, which suggest that a different mechanism may be involved in OSA development in preschool and school-age children. WHAT IS KNOWN: Various risk factors have been reported in obese children with OSA owing to the different age and different study design. Obese children have a higher prevalence and severity of obstructive sleep apnea (OSA). OSA risk factors in obese children are affected by different ages and study designs. WHAT IS NEW: A differential prevalence and risk factors for obese preschool and school-age children with OSA has been demonstrated.