Dynamic effects of interacting genes underlying rice flowering-time phenotypic plasticity and global adaptation.

The phenotypic variation of living organisms is shaped by genetics, environment, and their interaction. Understanding phenotypic plasticity under natural conditions is hindered by the apparently complex environment and the interacting genes and pathways. Herein, we report findings from the dissection of rice flowering-time plasticity in a genetic mapping population grown in natural long-day field environments. Genetic loci harboring four genes originally discovered for their photoperiodic effects (Hd1, Hd2, Hd5, and Hd6) were found to differentially respond to temperature at the early growth stage to jointly determine flowering time. The effects of these plasticity genes were revealed with multiple reaction norms along the temperature gradient. By coupling genomic selection and the environmental index, accurate performance predictions were obtained. Next, we examined the allelic variation in the four flowering-time genes across the diverse accessions from the 3000 Rice Genomes Project and constructed haplotypes at both individual-gene and multigene levels. The geographic distribution of haplotypes revealed their preferential adaptation to different temperature zones. Regions with lower temperatures were dominated by haplotypes sensitive to temperature changes, whereas the equatorial region had a majority of haplotypes that are less responsive to temperature. By integrating knowledge from genomics, gene cloning and functional characterization, and environment quantification, we propose a conceptual model with multiple levels of reaction norms to help bridge the gaps among individual gene discovery, field-level phenotypic plasticity, and genomic diversity and adaptation.

Foliar Spraying of Chlorpyrifos Triggers Plant Production of Linolenic Acid Recruiting Rhizosphere Bacterial Sphingomonas sp.

Plants have developed an adaptive strategy for coping with biotic or abiotic stress by recruiting specific microorganisms from the soil pool. Recent studies have shown that the foliar spraying of pesticides causes oxidative stress in plants and leads to changes in the rhizosphere microbiota, but the mechanisms by which these microbiota change and rebuild remain unclear. Herein, we provide for the first-time concrete evidence that rice plants respond to the stress of application of the insecticide chlorpyrifos (CP) by enhancing the release of amino acids, lipids, and nucleotides in root exudates, leading to a shift in rhizosphere bacterial community composition and a strong enrichment of the genus Sphingomonas sp. In order to investigate the underlying mechanisms, we isolated a Sphingomonas representative isolate and demonstrated that it is both attracted by and able to consume linolenic acid, one of the root exudates overproduced after pesticide application. We further show that this strain selectively colonizes roots of treated plants and alleviates pesticide stress by degrading CP and releasing plant-beneficial metabolites. These results indicate a feedback loop between plants and their associated microbiota allowing to respond to pesticide-induced stress.

Infection Characteristics and Drug Susceptibility of Multidrug-Resistant Bacteria in Patients with Diabetic Foot Ulcers.

BACKGROUND: We aimed to analyze the infection characteristics of multidrug-resistant organisms (MDROs) and their resistance to antibiotics in patients with diabetic foot and provide guidance for the use of antibiotics in clinical practice. METHODS: The clinical data of 737 patients with diabetic foot who were hospitalized at our institution from February 2020 to January 2023 were retrospectively analyzed. Purulent secretions were collected from the patient's ulcers and bacterial culture, identification, and drug susceptibility tests were performed. The multidrug resistance (MDR) rate of different bacteria, composition ratio of MDROs, drug resistance characteristics of the main MDROs, distribution characteristics of multidrug-resistant gram-positive cocci and gram-negative bacilli in patients with different Wagner Grades, MDR in patients with different Wagner Grades, bacterial infection rate, and other indicators were analyzed. RESULTS: Pathogenic bacteria from wound secretions of 505 patients were cultured, and 509 pathogenic bacteria were obtained. Among the pathogenic bacteria, 225 strains were gram-positive cocci, of which 172 (76.44%) were MDROs, and 284 were gram-negative bacilli, of which 232 (81.69%) were MDROs. Among the 404 multidrug-resistant strains, gram-positive cocci and gram-negative bacilli accounted for 42.57% and 57.43%, respectively. The top five dominant MDROs were Staphylococcus aureus (18.56%), coagulase-negative Staphylococcus (10.89%), Escherichia coli (10.15%), Proteus mirabilis (8.17%), Proteus vulgaris (6.19%), and Pseudomonas aeruginosa (6.19%). Staphylococcus aureus and coagulase-negative Staphylococcus were more resistant to penicillin, oxacillin, erythromycin, azithromycin, and clarithromycin, with resistance rates of 50.0 - 95.0%. The resistance rates of E. coli to ampicillin, cefazolin, cefuroxime, ceftriaxone, and cefepime were > 75%. With an increase in Wagner Grade, the proportion of gram-negative bacilli among the pathogenic bacteria of MDROs increased significantly (p < 0.05), as did the infection rate of MDROs in patients with diabetic foot (χ2 = 14.045, p < 0.05). CONCLUSIONS: MDROs in patients with diabetic foot are mainly gram-negative bacilli, followed by gram-positive cocci. The drug resistance of various MDROs varies greatly. With the increase in Wagner Grade and MDR of diabetic foot patients, the infection rate of drug-resistant bacteria has increased significantly. Therefore, clinicians should use drugs rationally according to drug sensitivity results.

Phenotypic plasticity in plant height shaped by interaction between genetic loci and diurnal temperature range.

Phenotypic plasticity is observed widely in plants and often studied with reaction norms for adult plant or end-of-season traits. Uncovering genetic, environmental and developmental patterns behind the observed phenotypic variation under natural field conditions is needed. Using a sorghum (Sorghum bicolor) genetic population evaluated for plant height in seven natural field conditions, we investigated the major pattern that differentiated these environments. We then examined the physiological relevance of the identified environmental index by investigating the developmental trajectory of the population with multistage height measurements in four additional environments and conducting crop growth modelling. We found that diurnal temperature range (DTR) during the rapid growth period of sorghum development was an effective environmental index. Three genetic loci (Dw1, Dw3 and qHT7.1) were consistently detected for individual environments, reaction-norm parameters across environments and growth-curve parameters through the season. Their genetic effects changed dynamically along the environmental gradient and the developmental stage. A conceptual model with three-dimensional reaction norms was proposed to showcase the interconnecting components: genotype, environment and development. Beyond genomic and environmental analyses, further integration of development and physiology at the whole-plant and molecular levels into complex trait dissection would enhance our understanding of mechanisms underlying phenotypic variation.

Polymorphisms in the DC-SIGN gene and their association with the severity of hand, foot, and mouth disease caused by enterovirus 71.

Severe hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection is associated with high mortality and disability. DC-SIGN, a receptor for EV71, is widely distributed in dendritic cells and may influence the severity of HFMD caused by EV71 infection. This observational study attempts to explore whether single-nucleotide polymorphisms (SNPs) in DC-SIGN are related to the severity of EV71-associated HFMD. Based on linkage disequilibrium and functional predictions, two DC-SIGN SNPs were selected and tested to explore their potential association with the severity of HFMD caused by EV71 infection. Two hundred sixteen Han Chinese children with HFMD caused by EV71 were enrolled to obtain clinical data, including the severity of HFMD, serum DC-SIGN levels, and DC-SIGN SNPs. We found a significant association between the rs7248637 polymorphism (A vs. G: OR = 0.644, 95% CI = 0.515-0.806) and the severity of HFMD caused by EV71 infection, as well as the rs4804800 polymorphism (A vs. G: OR = 1.539, 95% CI =1.229-1.928). These two DC-SIGN SNPs may have an effect on the severity of HFMD caused by EV71 infection.

Differential diagnosis of coronavirus disease 2019 pneumonia or influenza A pneumonia by clinical characteristics and laboratory findings.

BACKGROUND: Pneumonia caused by the 2019 novel Coronavirus (COVID-2019) shares overlapping signs and symptoms, laboratory findings, imaging features with influenza A pneumonia. We aimed to identify their clinical characteristics to help early diagnosis. METHODS: We retrospectively retrieved data for laboratory-confirmed patients admitted with COVID-19-induced or influenza A-induced pneumonia from electronic medical records in Ningbo First Hospital, China. We recorded patients' epidemiological and clinical features, as well as radiologic and laboratory findings. RESULTS: The median age of influenza A cohort was higher and it exhibited higher temperature and higher proportion of pleural effusion. COVID-19 cohort exhibited higher proportions of fatigue, diarrhea and ground-glass opacity and higher levels of lymphocyte percentage, absolute lymphocyte count, red-cell count, hemoglobin and albumin and presented lower levels of monocytes, c-reactive protein, aspartate aminotransferase, alkaline phosphatase, serum creatinine. Multivariate logistic regression analyses showed that fatigue, ground-glass opacity, and higher level of albumin were independent risk factors for COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count were independent risk factors for influenza A pneumonia. CONCLUSIONS: In terms of COVID-19 pneumonia and influenza A pneumonia, fatigue, ground-glass opacity, and higher level of albumin tend to be helpful for diagnosis of COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count tend to be helpful for the diagnosis of influenza A pneumonia.

Genomic and environmental determinants and their interplay underlying phenotypic plasticity.

Observed phenotypic variation in living organisms is shaped by genomes, environment, and their interactions. Flowering time under natural conditions can showcase the diverse outcome of the gene-environment interplay. However, identifying hidden patterns and specific factors underlying phenotypic plasticity under natural field conditions remains challenging. With a genetic population showing dynamic changes in flowering time, here we show that the integrated analyses of genomic responses to diverse environments is powerful to reveal the underlying genetic architecture. Specifically, the effect continuum of individual genes (Ma1 , Ma6 , FT, and ELF3) was found to vary in size and in direction along an environmental gradient that was quantified by photothermal time, a combination of two environmental factors (photoperiod and temperature). Gene-gene interaction was also contributing to the observed phenotypic plasticity. With the identified environmental index to quantitatively connect environments, a systematic genome-wide performance prediction framework was established through either genotype-specific reaction-norm parameters or genome-wide marker-effect continua. These parallel genome-wide approaches were demonstrated for in-season and on-target performance prediction by simultaneously exploiting genomics, environment profiling, and performance information. Improved understanding of mechanisms for phenotypic plasticity enables a concerted exploration that turns challenge into opportunity.

Fractionated carbon dioxide (CO2) laser treatment contributes to trans-nail penetration of rhodamine B and changes of cytokine microenvironment.

This study is to determine the role of the fractional CO2 laser in topical drug delivery and the impact of local immune responses. Experimental rabbit nails were treated with fractionated CO2 laser at varied fluencies of 20 mJ, 25 mJ, and 30 mJ and half of which were coated with rhodamine B (RhB). Histological examination was performed by hematoxylin and eosin staining; the penetration of RhB was assessed by the use of confocal laser scanning microscopy; and the expressions of IFN-γ and IL-4 mRNA in situ were detected by means of qPCR at 12 h, 24 h, 3 days, and 7 days post-laser irritation. The fractional CO2 laser could generate microscopic treatment zones in nail plates, and the depths of these micropores as well as the permeation of RhB in nails increased significantly in an energy-dependent manner. Importantly, the laser irritation led an upregulation of local IFN-γ mRNA expression accompanied by a downregulation of IL-4 mRNA expression. The ultrapulsed ablative fractionated CO2 laser may assist topical drug delivery, and may drive stronger local Th1 responses due to an imbalance of IFN-γ/IL-4 expressions, suggesting that the combination of ablative fractionated CO2 laser with topical agents would be an effective option for the treatment of onychomycosis.

[Textual research on classical prescriptions in Mongolian medicine].

Mongolians have a long history of using prescriptions, which can be classified into four stages as follows: the germination and experience accumulation stage before the 13 th century, the theoretical formation stage from the 13 th to 16 th century, the rapid development stage from the 17 th to 20 th century, and the leaping development stage from the mid-20 th century to the present. The prescriptions from the ancient classical or representative medical books have always been used by Mongolian physicians for generations, and they are still in use due to the definite curative effects. In 2008, the Notice on Issuing the Supplementary Provisions to the Registration and Management of Traditional Chinese Medicine(TCM) described that China has attached more importance to the excavation and development of classical prescriptions. As stipulated in the Law of the People's Republic of China on Traditional Chinese Medicine, the classical prescriptions should be those available in ancient TCM classics and still in wide use, with exact curative effects, distinct features, and obvious advantages. This paper expounded the historical formation and development of classical prescriptions in Mongo-lian medicine, introduced the five most influential ancient medical books revealing the formation and development of these classic prescriptions, and traced the origin of such classical prescriptions as Wenguanmu Siwei Decoction, Shouzhangshen Bawei Decoction, Jianghuang Siwei Decoction and summarized the origin, development history and characteristics of classical prescriptions in Mongolian medicine, aiming to provide a reference for their further research and development.

Association of gene polymorphisms of CD55 with susceptibility to and severity of hand, foot, and mouth disease caused by enterovirus 71 in the Han Chinese population.

Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) can lead to high morbidity and mortality, and genetic background plays an important role during the disease process. We investigated the association between the single-nucleotide polymorphism (SNP) rs2564978 of the CD55 gene and susceptibility to and severity of HFMD using the SNPs can multiple SNP typing methods. Soluble CD55 (sCD55) expression was significantly lower in the EV71 HFMD group than in the control group and lower in severe cases than in mild cases (P < .001). Moreover, CD55 rs2564978 (C vs T OR = 1.300, 95% CI, 1.120-1.509) was associated with the risk of EV71 infection, and genotype TC was related to the severity of the infection (TC vs TT OR = 4.523, 95% CI, 2.033-10.066). Our results suggest that sCD55 expression and the CD55 polymorphism rs2564978 may influence the susceptibility to and severity of EV71 infection.

Association of polymorphisms in the vitamin D receptor gene with susceptibility to and severity of hand, foot, and mouth disease caused by coxsackievirus A16.

Coxsackievirus A16 (CA16) remains the most common causative agent of hand, foot, and mouth disease (HFMD), and is related to high incidence and critical complications. Vitamin D receptor (VDR) activity might affect the outcome of CA16 infection. Our case-control research aims to evaluate the relationship between VDR polymorphisms in the gene encoding and susceptibility to and severity of HFMD due to CA16. Three single-nucleotide polymorphisms (SNPs) of VDR gene were selected according to functional prediction and linkage disequilibrium, and were examined utilizing the SNPscan method to identify possible associations with HFMD caused by CA16. A significant relationship was found in the HFMD cases of polymorphism rs11574129 (GA vs GG: odds ratio (OR) = 0.068, 95% confidence interval (CI) = 0.007-0.693, P = .023; GA + AA vs GG: OR = 0.322, 95%CI = 0.106-0.984, P = .047), and vitamin D levels in genotype AA were significantly higher than those in genotype GG (P < .05). These results suggest that VDR rs11574129 may influence genetic susceptibility to CA16-associated HFMD.

Vitamin D receptor gene methylation in patients with hand, foot, and mouth disease caused by enterovirus 71.

To evaluate the epigenetic regulation of the VDR gene in enterovirus 71 (EV71)-associated severe hand, foot, and mouth disease (HFMD), a total of 116 patients with EV71-HFMD, including 58 with mild EV71-HFMD and 58 with severe EV71-HFMD, as well as 60 healthy controls, were enrolled in this study. Quantitative real-time PCR was used to measure the relative levels of VDR mRNA expression, and the methylation status of the VDR promoter was assessed using a MethylTarget™ assay. The DNA methylation levels of the VDR promoter in children with EV71-associated severe HFMD were lower than those in the healthy controls and in children with mild HFMD (P < 0.05). Hypomethylation at CpG site 133 and hypermethylation at the CpG 42 sites and 68 downregulated VDR expression. Moreover, the methylation level of VDR could be used for differential diagnosis of mild and severe EV71-associated HFMD (AUC56, 0.73; AUC68, 0.699; AUC42, 0.694; AUC66, 0.693). VDR expression and promoter methylation were associated with the progression of EV71 infection. Determining the VDR promoter status might help clinicians initiate the appropriate strategy for treatment of EV71-associated HFMD.

Fruit weight is controlled by Cell Size Regulator encoding a novel protein that is expressed in maturing tomato fruits.

Increases in fruit weight of cultivated vegetables and fruits accompanied the domestication of these crops. Here we report on the positional cloning of a quantitative trait locus (QTL) controlling fruit weight in tomato. The derived allele of Cell Size Regulator (CSR-D) increases fruit weight predominantly through enlargement of the pericarp areas. The expanded pericarp tissues result from increased mesocarp cell size and not from increased number of cell layers. The effect of CSR on fruit weight and cell size is found across different genetic backgrounds implying a consistent impact of the locus on the trait. In fruits, CSR expression is undetectable early in development from floral meristems to the rapid cell proliferation stage after anthesis. Expression is low but detectable in growing fruit tissues and in or around vascular bundles coinciding with the cell enlargement stage of the fruit maturation process. CSR encodes an uncharacterized protein whose clade has expanded in the Solanaceae family. The mutant allele is predicted to encode a shorter protein due to a 1.4 kb deletion resulting in a 194 amino-acid truncation. Co-expression analyses and GO term enrichment analyses suggest association of CSR with cell differentiation in fruit tissues and vascular bundles. The derived allele arose in Solanum lycopersicum var cerasiforme and appears completely fixed in many cultivated tomato's market classes. This finding suggests that the selection of this allele was critical to the full domestication of tomato from its intermediate ancestors.

[Correlation between chemical composition,ecological factors and soil factors of Chinese herbal medicine Daphnes Cortex].

In this paper, the correlation between the chemical constituents of Chinese herbal medicines Daphnes Cortex and the ecological factors and soil factors was studied, which provided a reference for the selection of suitable areas for artificial cultivation of Daphne giraldii and wild tending. The geographic information system(GIS) was applied to obtain the ecological factor information of 23 collection sites of Daphnes Cortex, and the soil factor information was determined by the standard procedure in the soil test standard manual. Combining the information of 93 chemical constituents of Daphnes Cortex in 23 collection sites the correlation between components and ecological factors and soil factors was analyzed by statistical methods. The correlation analysis showed that the longitude, annual average rainfall, annual sunshine intensity, annual average temperature in the ecological factors, soil type, effective copper and pH value were the dominant factors affecting the chemical composition of Daphnes Cortex.

Association of polymorphisms in the vitamin D receptor gene with severity of hand, foot, and mouth disease caused by enterovirus 71.

Severe hand, foot, and mouth disease (HFMD) is sometimes associated with critical complications that can cause substantial child mortality. Activity of the vitamin D receptor (VDR) may influence the outcomes of enterovirus 71 (EV71) infection. This case-control study aimed to assess the association of single-nucleotide polymorphisms (SNPs) in the gene encoding the VDR with the severity of EV71-associated HFMD. We selected four VDR SNPs based on linkage disequilibrium and functional prediction, and we tested them using the SNPscan multiple SNP typing method for potential association with severity of EV71-associated HFMD. We found a significant association in the case of rs11574129 (G vs A: odds ratio (OR), 0.3439; 95% confidence intervals (CI), 0.1778-0.6653) and rs739837 (T vs G: OR, 0.5580; 95%CI, 0.3352-0.9291). Our results suggest that these two SNPs may influence the severity of EV71-associated HFMD.

Radiomics model of contrast-enhanced computed tomography for predicting the recurrence of acute pancreatitis.

OBJECTIVES: To predict the recurrence of acute pancreatitis (AP) by constructing a radiomics model of contrast-enhanced computed tomography (CECT) at AP first attack. METHODS: We retrospectively enrolled 389 first-attack AP patients (271 in the primary cohort and 118 in the validation cohort) from three tertiary referral centers; 126 and 55 patients endured recurrent attacks in each cohort. Four hundred twelve radiomics features were extracted from arterial and venous phase CECT images, and clinical characteristics were gathered to develop a clinical model. An optimal radiomics signature was chosen using a multivariable logistic regression or support vector machine. The radiomics model was developed and validated by incorporating the optimal radiomics signature and clinical characteristics. The performance of the radiomics model was assessed based on its calibration and classification metrics. RESULTS: The optimal radiomics signature was developed based on a multivariable logistic regression with 10 radiomics features. The classification accuracy of the radiomics model well predicted the recurrence of AP for both the primary and validation cohorts (87.1% and 89.0%, respectively). The area under the receiver operating characteristic curve (AUC) of the radiomics model was significantly better than that of the clinical model for both the primary (0.941 vs. 0.712, p = 0.000) and validation (0.929 vs. 0.671, p = 0.000) cohorts. Good calibration was observed for all the models (p > 0.05). CONCLUSIONS: The radiomics model based on CECT performed well in predicting AP recurrence. As a quantitative method, radiomics exhibits promising performance in terms of alerting recurrent patients to potential precautions. KEY POINTS: • The incidence of recurrence after an initial episode of acute pancreatitis is high, and quantitative methods for predicting recurrence are lacking. • The radiomics model based on contrast-enhanced computed tomography performed well in predicting the recurrence of acute pancreatitis. • As a quantitative method, radiomics exhibits promising performance in terms of alerting recurrent patients to the potential need to take precautions.

[Interference of Lumican Regulates the Invasion and Migration of Liver Cancer Cells].

OBJECTIVE: To explore the effect of silencing lumican on the invasion and migration of liver cancer cells. METHODS: Lumican was silenced by shRNA in liver cancer cells (HepG2 and MHCC97H). The mRNA levels of lumican were detected by qRT-PCR. Cell invasion was measured by Transwell. Cell migration was tested via wound healing. The protein levels of lumican,MMP-9,VEGF,ERK1,JNK,p-ERK1 and p-JNK were measured by Western blot. RESULTS: Liver cancer cells (HepG2 and MHCC97H) had higher levels of mRNA and protein of lumican compared with normal hepatocyte L02 (P<0.01). shRNA lowered the levels of mRNA and protein of lumican (P<0.01),and weakened the invasion and migration of cancer cells (P<0.01). The expressions of MMP-9 and VEGF decreased with the shRNA silence (P<0.01). shRNA also reduced the protein level of p-ERK1 and p-JNK (P<0.01). CONCLUSION: Silencing lumican by shRNA attenuates the invasion and migration of liver cancer cells via inhibiting the activation of ERK1/JNK pathway.

High-speed countercurrent chromatography isolation of flavans from Ixeris chinensis and their identification by NMR spectroscopy.

High-speed countercurrent chromatography, combined with macroporous resin chromatography were applied to the separation and purification of flavans from Ixeris chinensis. Four flavans, namely, 5-methoxy-7,4'-dihydroxyflavan-3-ol (1), 5,7-dimethoxy-4'-hydroxyflavan-3-ol (2), 5,7-dimethoxy-4'-hydroxyflavan (3), and 5,7-dimethoxy-8-methyl-4'-hydroxyflavan (4), were obtained from I. chinensis for the first time. Their chemical structural identification was carried out by spectroscopic methods, including 1D and 2D NMR spectroscopy. Amounts of 13.2 mg of compound 1, 6.4 mg of compound 2, 5.8 mg of compound 3, and 14.5 mg of compound 4 were separated from 120 mg 75% ethanol fraction. The purities of 1-4 were 99.1, 99.2, 97.3, and 98.6 %, respectively.

High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia.

The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1/2 expression in 320 patients with cytogenetically normal AML (CN-AML) by quantitative real-time reverse-transcription polymerase chain reaction. High expression of IDH1 was predominant in patients with FLT3-ITD and DNMT3A mutations and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of microRNA 181 family. Prognosis was adversely affected by high IDH1 expression, with shorter overall survival and event-free survival in the context of clinical characteristics, including age, WBC count, and gene mutations of NPM1, FLT3-ITD, CEBPA, IDH1, IDH2 and DNMT3A in CN-AML. Moreover, the clinical outcome of IDH1 expression in terms of overall survival, event-free survival and complete remission rate still remained in multivariate models in CN-AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG-1999 protocol. Our results demonstrated that high IDH1 expression is associated with a poor prognosis of CN-AML.