ABSTRACT
Advancements in mass spectrometry (MS)-based proteomics have greatly facilitated the large-scale quantification of proteins and microproteins, thereby revealing altered signalling pathways across many different cancer types. However, specialized and comprehensive resources are lacking for cancer proteomics. Here, we describe CancerProteome (http://bio-bigdata.hrbmu.edu.cn/CancerProteome), which functionally deciphers and visualizes the proteome landscape in cancer. We manually curated and re-analyzed publicly available MS-based quantification and post-translational modification (PTM) proteomes, including 7406 samples from 21 different cancer types, and also examined protein abundances and PTM levels in 31 120 proteins and 4111 microproteins. Six major analytical modules were developed with a view to describe protein contributions to carcinogenesis using proteome analysis, including conventional analyses of quantitative and the PTM proteome, functional enrichment, protein-protein associations by integrating known interactions with co-expression signatures, drug sensitivity and clinical relevance analyses. Moreover, protein abundances, which correlated with corresponding transcript or PTM levels, were evaluated. CancerProteome is convenient as it allows users to access specific proteins/microproteins of interest using quick searches or query options to generate multiple visualization results. In summary, CancerProteome is an important resource, which functionally deciphers the cancer proteome landscape and provides a novel insight for the identification of tumor protein markers in cancer.
Subject(s)
Databases, Protein , Neoplasms , Proteome , Humans , Mass Spectrometry/methods , Neoplasms/chemistry , Neoplasms/genetics , Protein Processing, Post-Translational , Proteome/analysis , Proteomics/methodsABSTRACT
MOTIVATION: Constructing a phylogenetic tree requires calculating the evolutionary distance between samples or species via large-scale resequencing data, a process that is both time-consuming and computationally demanding. Striking the right balance between accuracy and efficiency is a significant challenge. RESULTS: To address this, we introduce a new algorithm, MIKE (MinHash-based k-mer algorithm). This algorithm is designed for the swift calculation of the Jaccard coefficient directly from raw sequencing reads and enables the construction of phylogenetic trees based on the resultant Jaccard coefficient. Simulation results highlight the superior speed of MIKE compared to existing state-of-the-art methods. We used MIKE to reconstruct a phylogenetic tree, incorporating 238 yeast, 303 Zea, 141 Ficus, 67 Oryza, and 43 Saccharum spontaneum samples. MIKE demonstrated accurate performance across varying evolutionary scales, reproductive modes, and ploidy levels, proving itself as a powerful tool for phylogenetic tree construction. AVAILABILITY AND IMPLEMENTATION: MIKE is publicly available on Github at https://github.com/Argonum-Clever2/mike.git.
Subject(s)
Algorithms , Phylogeny , Computer Simulation , Sequence Analysis, DNAABSTRACT
Single-cell transcriptome has enabled the transcriptional profiling of thousands of immune cells in complex tissues and cancers. However, subtle transcriptomic differences in immune cell subpopulations and the high dimensionality of transcriptomic data make the clustering and annotation of immune cells challenging. Herein, we introduce ImmCluster (http://bio-bigdata.hrbmu.edu.cn/ImmCluster) for immunology cell type clustering and annotation. We manually curated 346 well-known marker genes from 1163 studies. ImmCluster integrates over 420 000 immune cells from nine healthy tissues and over 648 000 cells from different tumour samples of 17 cancer types to generate stable marker-gene sets and develop context-specific immunology references. In addition, ImmCluster provides cell clustering using seven reference-based and four marker gene-based computational methods, and the ensemble method was developed to provide consistent cell clustering than individual methods. Five major analytic modules were provided for interactively exploring the annotations of immune cells, including clustering and annotating immune cell clusters, gene expression of markers, functional assignment in cancer hallmarks, cell states and immune pathways, cell-cell communications and the corresponding ligand-receptor interactions, as well as online tools. ImmCluster generates diverse plots and tables, enabling users to identify significant associations in immune cell clusters simultaneously. ImmCluster is a valuable resource for analysing cellular heterogeneity in cancer microenvironments.
Subject(s)
Gene Expression Profiling , Immune System , Humans , Cluster Analysis , Gene Expression Profiling/methods , Neoplasms/genetics , Neoplasms/immunology , Transcriptome , Tumor Microenvironment/genetics , Immune System/cytology , Cell Communication , Genetic MarkersABSTRACT
Superhydrophobic surfaces have attracted significant attention for their ability to prevent ice formation and facilitate deicing without requiring external energy. However, these surfaces are often vulnerable to damage from external forces, leading to functional failure due to poor mechanical stability, which limits their widespread use. Drawing inspiration from the hierarchical groove of rose petals and the micropapillae of lotus leaves, a simple laser-based method is proposed to create a superhydrophobic surface with a micro/nano hierarchical crater-like structure (HCLS). To enhance the surface, boiling water treatment is applied to induce dense nanostructures, resulting in an optimal contact angle (CA) of 162° and a desirable sliding angle (SA) of 2.0°. The initial ice adhesion strength of HCLS is as low as 1.4 kPa and remains below 10 kPa even after 300 cm sandpaper abrasion. Furthermore, the HCLS demonstrates excellent mechanical durability, maintaining its performance under conditions that simulate the continuous impact of water and sand in extreme weather. This approach offers an innovative design concept that has the potential to advance the development of anti-icing and deicing surfaces for future aircraft.
ABSTRACT
The employment of liquid chromatography-mass spectrometry (LC-MS) untargeted and targeted metabolomics has led to the discovery of novel biomarkers and improved the understanding of various disease mechanisms. Numerous strategies have been reported to expand the metabolite coverage in LC-MS-untargeted and targeted metabolomics. To improve the sensitivity of low-abundance or poor-ionized metabolites for reducing the amount of clinical sample, chemical derivatization methods are used to target different functional groups. Proper sample preparation is beneficial for reducing the matrix effect, maintaining the stability of the LC-MS system, and increasing the metabolite coverage. Machine learning has recently been integrated into the workflow of LC-MS metabolomics to accelerate metabolite identification and data-processing automation, and increase the accuracy of disease classification and clinical outcome prediction. Due to the rapidly growing utility of LC-MS metabolomics in discovering disease markers, this review will address the recent advances in the field and offer perspectives on various strategies for expanding metabolite coverage, chemical derivatization, sample preparation, clinical disease markers, and machining learning for disease modeling.
ABSTRACT
BACKGROUND: Previous studies have suggested that oil-based contrast agents used during hysterosalpingography (HSG) in infertile patients can enhance fertility. However, limited research has investigated the effect of oil-based contrast medium specifically in individuals with endometriosis-related infertility. OBJECTIVE: This study aims to explore the impact of oil-based contrast medium on fertility outcomes in women with endometriosis-related infertility. METHODS: Conducted at the First Affiliated Hospital of Guangxi Medical University (January 2020 to June 2022), the study included 512 patients undergoing HSG. Patients were categorized into oil-based and non-oil-based groups, and after propensity score matching, demographic characteristics were compared. Main outcomes included clinical pregnancy rates, live birth rates, early miscarriage rates, and ectopic pregnancy rates. RESULTS: In our analysis, the Oil-based group showed significantly better outcomes compared to the Non-oil-based group. Specifically, the Oil-based group had higher clinical pregnancy rates (51.39% vs. 27.36%) and increased live birth rates (31.48% vs. 19.93%). This trend held true for expectant treatment, IUI, and IVF/ICSI, except for surgical treatment where no significant difference was observed. After adjusting for various factors using propensity score matching, the Non-oil-based group consistently exhibited lower clinical pregnancy rates compared to the Oil-based group. The Odds Ratio (OR) was 0.38 (95%CI: 0.27-0.55) without adjustment, 0.34 (0.22-0.51) in multivariable analysis, 0.39 (0.27-0.57) using inverse probability of treatment weighting (IPTW), and 0.22 (0.14-0.35) in propensity score matching. CONCLUSION: Oil-based contrast medium used in HSG for women with endometriosis-related infertility is associated with higher clinical pregnancy rates and live birth rates compared to Non-oil-based contrast medium.
Subject(s)
Endometriosis , Infertility, Female , Pregnancy , Humans , Female , Contrast Media , Hysterosalpingography , Endometriosis/complications , Endometriosis/diagnostic imaging , Infertility, Female/diagnostic imaging , Infertility, Female/etiology , Infertility, Female/therapy , Retrospective Studies , China/epidemiology , Fertility , Pregnancy Rate , Live BirthABSTRACT
PURPOSE: Sulbactam (SBT) is one of the most significant treatments for patients with extensively drug-resistant Acinetobacter baumannii (XDR-AB). However, the efficacy and safety of SBT and its high dose regimen has not been well documented. This retrospective study aimed to assess the efficacy and safety of SBT-based treatment, particularly at high-dose (≥ 6 g/day), for XDR-AB infection. METHOD: A total of 52 XDR-AB infected patients treated with intravenous SBT at Peking Union Medical College Hospital were included. The primary outcome was 28-day all-cause mortality, while the secondary outcome was 14-day clinical response and the time of response. The formulation of SBT in our study is 0.5 g per vial. RESULTS: Among the patients, the 28-day all-cause mortality rate was 36.5% (19/52), and the favorable 14-day clinical response rate was 59.6% (31/52). The 28-day mortality was independently associated coinfection with gram-positive bacteria (GPB) and a shorter duration of therapy. Patients with intracranial infection might have a longer survival time. A favorable 14-day clinical response was associated with the dose of SBT, and a longer treatment duration. However, the higher creatinine clearance (CrCl) associated with a worse clincal response. In addition, a higher SBT dosage was significantly correlated with a shorter time to clinical response. No adverse effects related were reported. CONCLUSION: The single-agent formulation of SBT emerges as a promising alternative for the treatment of XDR-AB infection, such as intracranial infection, particularly at high doses (≥ 6 g/day). Besides, longer duration of treatment correlates with higher survival rate and better favorable clinical response. Higher CrCl negatively correlates with favorable clinical response.
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BACKGROUND: Keloids are common benign skin lesions originating from a disorganized fibroproliferative collagen response; these lesions often lead to both physical and psychological problems. The optimal treatment for keloids is yet to be standardized. Intralesional injection, which is simple and nontraumatic, is one of the most commonly used treatment modalities for these lesions. In this study, we compared 5 different drugs (intralesional injections) for the treatment of keloids in terms of efficacy. METHODS: We systemically searched relevant studies on PubMed, EMBASE, and Cochrane Library. Randomized clinical trials on the safety and efficacy of triamcinolone acetonide (TAC), 5-fluorouracil (5-FU), botulinum toxin A (BTA), verapamil, and bleomycin were included in this study. RESULTS: This network meta-analysis included a total of 1114 patients from 20 randomized controlled trials. Botulinum toxin A alone and TAC plus 5-FU exhibited significantly better efficacy than did 5-FU, TAC, and verapamil. No significant difference in efficacy between BTA alone and TAC combined with 5-FU was observed. No significant differences were noted in the adverse event rate between BTA, TAC plus 5-FU, 5-FU, and TAC. Furthermore, we performed surface under the cumulative ranking curve analyses to predict the rank of each intervention (by efficacy and adverse event rate). The predicted ranking by efficacy was as follows: TAC plus 5-FU, BTA, bleomycin, TAC, 5-FU, and verapamil; the predicted ranking by adverse events was as follows: TAC, 5-FU, TAC plus 5-FU, and BTA. Funnel plot analysis revealed no publication bias. CONCLUSIONS: Botulinum toxin A and TAC plus 5-FU appear to have outstanding therapeutic efficacy for keloids. The rate of adverse events was similar among BTA, TAC, 5-FU, and TAC plus 5-FU. Nonetheless, additional reviews of rigorous, large-scale randomized controlled trials are warranted for further validation of our findings.
Subject(s)
Botulinum Toxins, Type A , Keloid , Humans , Keloid/drug therapy , Keloid/pathology , Botulinum Toxins, Type A/therapeutic use , Network Meta-Analysis , Drug Therapy, Combination , Treatment Outcome , Fluorouracil/therapeutic use , Injections, Intralesional , Bleomycin/therapeutic use , Verapamil/therapeutic use , Randomized Controlled Trials as TopicABSTRACT
A near-infrared (NIR) sub-ppm level photoacoustic sensor for hydrogen sulfide (H2S) using a differential Helmholtz resonator (DHR) as the photoacoustic cell (PAC) was presented. The core detection system was composed of a NIR diode laser with a center wavelength of 1578.13â nm, an Erbium-doped optical fiber amplifier (EDFA) with an output power of â¼120â mW, and a DHR. Finite element simulation software was used to analyze the influence of the DHR parameters on the resonant frequency and acoustic pressure distribution of the system. Through simulation and comparison, the volume of the DHR was 1/16 that of the conventional H-type PAC for a similar resonant frequency. The performance of the photoacoustic sensor was evaluated after optimizing the DHR structure and modulation frequency. The experimental results showed that the sensor had an excellent linear response to the gas concentration and the minimum detection limit (MDL) for H2S detection in differential mode can reach 460.8 ppb.
ABSTRACT
BACKGROUND: Survival rates of young women undergoing cancer treatment have substantially improved, with a focus on post-treatment quality of life. Ovarian tissue transplantation (OTT) is a viable option to preserve fertility; however, there is no consensus on the optimal transplantation site. Most studies on OTT are nonrandomized controlled trials with limited sample sizes and uncontrolled statistical analyses, leaving the question of which transplant site yields the highest chance of achieving a live birth unanswered. OBJECTIVE: This meta-analysis aimed to assess the effect of different ovarian transplant sites on postoperative reproductive outcomes. METHODS: We adhered to the PRISMA Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Systematic searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 17, 2023. The inclusion criteria were as follows: (1) women who underwent OTT with a desire for future childbirth, and (2) reports of specific transplant sites and corresponding pregnancy outcomes. The exclusion criteria included the inability to isolate or extract relevant outcome data, case reports, non-original or duplicate data, and articles not written in English. RESULTS: Twelve studies (201 women) were included in the meta-analysis of cumulative live birth rates (CLBR) after OTT. The CLBR, which encompasses both spontaneous pregnancies and those achieved through assisted reproductive technology (ART) following OTT to the ovarian site, was 21% (95% CI: 6-40, I2: 52.81%, random effect). For transplantation to the pelvic site, the live birth rate was 30% (95% CI: 20-40, I2: 0.00%, fixed effect). Combining transplantation to both the pelvic and ovarian sites resulted in a live birth rate of 23% (95% CI: 11-36, I2: 0.00%, fixed effect). Notably, heterotopic OTT yielded a live birth rate of 3% (95% CI: 0-17, I2: 0.00%, fixed effect). CONCLUSION: Pregnancy outcomes were not significantly different after orthotopic ovarian transplantation, and pregnancy and live birth rates after orthotopic OTT were significantly higher than those after ectopic transplantation. REGISTRATION NUMBER: INPLASY202390008.
Subject(s)
Ovary , Quality of Life , Pregnancy , Female , Humans , Reproductive Techniques, Assisted , Pregnancy Outcome , Pregnancy, Multiple , Live Birth , Pregnancy RateABSTRACT
BACKGROUND: Contrast-enhanced computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the primary modalities to assess donors' vessels before transplant surgery. Radiation and contrast medium are potentially harmful to donors. PURPOSE: To compare the image quality and visualization scores of hepatic arteries on CTA and balanced steady-state free-precession (bSSFP) non-contrast-enhanced MRA (NC-MRA), and to evaluate if bSSFP NC-MRA can potentially be a substitute for CTA. STUDY TYPE: Prospective. POPULATION: Fifty-six consecutive potential living-related liver donors (30.9 ± 8.4 years; 31 men). FIELD STRENGTH/SEQUENCE: 1.5T; four bSSFP NC-MRA sequences: respiratory-triggered (Inhance inflow inversion recovery [IFIR]) and three breath-hold (BH); and CTA. ASSESSMENT: The artery-to-liver contrast (Ca-l) was quantified. Three radiologists independently assigned visualization scores using a four-point scale to potential origins, segments, and branches of the hepatic arteries, determined the anatomical variants based on Hiatt's classification, and assessed the image quality of NC-MRA sequences. STATISTICAL TESTS: Fleiss' kappa to evaluate the readers' agreement. Repeat measured ANOVA or Friedman test to compare Ca-l of each NC-MRA. Friedman test to compare overall image quality and visualization scores; post hoc analysis using Wilcoxon signed-rank test. P-value <0.05 was considered statistically significant. RESULTS: Inhance IFIR Ca-l was significantly higher than all BH bSSFP Ca-l (0.56 [0.45-0.64] vs. 0.37 [0.29-0.47] to 0.41 [0.23-0.51]). Overall image quality score of BH bSSFP TI1200 was significantly higher than other NC-MRA (4 [4-4] vs. 4 [3 to 4-4]). The median visualization scores of almost all arteries on CTA were significantly higher than on NC-MRA (4 [3 to 4-4] vs. 1 [1-2] to 4 [4-4]). The median visualization scores were all 4 [4-4 ] on Inhance IFIR with >92.3% observed scores ≥3, except the segment 4 branch (3 [1-4], 53.6%). The identification rates of arterial variants were 92.9%-97% on Inhance IFIR. DATA CONCLUSIONS: Although CTA is superior to the NC-MRA, all NC-MRA depict the donor arterial anatomy well. Inhance IFIR can potentially be an alternative image modality for CTA to evaluate the arterial variants of living donors. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.
Subject(s)
Contrast Media , Living Donors , Male , Humans , Prospective Studies , Liver/diagnostic imaging , Liver/blood supply , Magnetic Resonance Angiography/methods , Tomography, X-Ray Computed , Reproducibility of ResultsABSTRACT
Kidney-yang-deficiency-syndrome (KYDS) is a metabolic disease caused by neuroendocrine disorder. Gushudan (GSD) is a traditional Chinese medicine prescription with the effect of nourishing kidney and strengthening bones. In this study, the mechanism of preventive effect of GSD on KYDS was explored by integrating metabolomics and serum pharmacochemistry. Reversed-phase/hydrophilic interaction chromatography-ultra-high-performance liquid chromatography-Quadrupole-Orbitrap high-resolution mass spectrometry (RP/HILIC-UHPLC-Q-Orbitrap HRMS)-based serum metabolomics indicated metabolic disturbances of KYDS rats, and 50 potential biomarkers including l-threonine, succinic acid and phytosphingosine were obtained, which were mainly involved in alanine, aspartate and glutamate metabolism, citrate cycle (tricarboxylic acid cycle) and glycerophospholipid metabolism, among others. Serum pharmacochemistry identified 29 prototypical ingredients and 9 metabolites of GSD after administration, such as icaritin and xanthotoxol. The combination of 10 serum migration ingredients in GSD, including icaritin and osthole, with 7 important targets, including AKT serine/threonine kinase 1 (AKT1) and MAPK14, was found to be key for GSD to prevent KYDS in the network pharmacology study. This study provided a new idea for the research of pathogenesis of diseases and the pharmacodynamic mechanism of traditional Chinese medicine.
Subject(s)
Drugs, Chinese Herbal , Rats , Animals , Drugs, Chinese Herbal/pharmacology , Metabolomics/methods , Yang Deficiency/metabolism , Kidney/metabolism , Biomarkers , Chromatography, High Pressure LiquidABSTRACT
The dibutyl phthalate (DBP) has been detected in fetuses and infants and can cause damage to the reproductive system in adulthood, but the exact mechanism remains unclear. Here, we aim to investigate the effects of intrauterine DBP exposure on offspring reproductive function and explore possible mechanisms. SPF C57BL/6 pregnant mice were given DBP (0.5, 5, 75 mg/kg/d) or corn oil from day 5 to day 19 by gavage. After weaning, the pups were fed a standard diet for 5 weeks. In addition, TM3 Leydig cell cultures were used to study the relevant mechanisms in vitro. The results showed that intrauterine DBP exposure could reduce sperm density and sperm motility, cause testicular tissue damage, down-regulate serum T and LH levels, and up-regulate serum FSH levels at 75 mg/kg/d. Western blot and methylation detection revealed intrauterine exposure to DBP down-regulated testosterone synthesis-related proteins StAR, P450scc, 3ß-HSD, PKA, and PKC expression, while up-regulated the levels of methyltransferase proteins expression and DNA 5-methylcytosine (5mC) in testicular tissue of mouse offspring at 75 mg/kg/d. Further detection found in utero 75 mg/kg/d DBP exposure down-regulated MGARP protein expression, and induced incomplete methylation of the MGARP gene. An in vitro analysis showed that MGARP inhibition is involved in an impaired testosterone synthesis in TM3 cells. Cell culture results suggest that MGARP down-regulation may be involved in impaired testosterone production in monobutyl phthalate-treated cells. The present study revealed that 75 mg/kg/d DBP exposure in utero resulted in testosterone synthesis disorders and reproductive function impairment in mouse offspring, and the mechanism may be related to DNA methylation-mediated down-regulation of MGARP in the testis.
Subject(s)
DNA Methylation , Dibutyl Phthalate , Animals , Female , Male , Mice , Pregnancy , Dibutyl Phthalate/pharmacology , Mice, Inbred C57BL , Semen/metabolism , Sperm Motility , Testis , TestosteroneABSTRACT
Suramin was originally used as an antiparasitic drug in clinics. Here, we demonstrate that suramin can bind to the N-terminal domain of SARS-CoV-2 nucleocapsid protein (N-NTD) and disturb its interaction with RNA. The BLI experiments showed that N-NTD interacts suramin with a dissociate constant (Kd = 2.74 µM) stronger than that of N-NTD with ssRNA-16 (Kd = 8.37 µM). Furthermore, both NMR titration experiments and molecular docking analysis suggested that suramin mainly binds to the positively charged cavity between the finger and the palm subdomains of N-NTD, and residues R88, R92, R93, I94, R95, K102 and A156 are crucial for N-NTD capturing suramin. Besides, NMR dynamics experiments showed that suramin-bound N-NTD adopts a more rigid structure, and the loop between ß2-ß3 exhibits fast motion on the ps-ns timescale, potentially facilitating suramin binding. Our findings not only reveal the molecular basis of suramin disturbing the association of SARS-CoV-2 N-NTD with RNA but also provide valuable structural information for the development of drugs against SARS-CoV-2.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/metabolism , Suramin/pharmacology , Nucleocapsid Proteins/chemistry , Molecular Docking Simulation , Models, Molecular , RNA, Viral/geneticsABSTRACT
BACKGROUND: Ageing and diabetes are growing global health burdens. The current understanding of cardiovascular disease (CVD) and mortality risk across the glycaemic spectrum in older populations is limited. OBJECTIVES: This study sought to characterise CVD and all-cause mortality risk across the glycaemic spectrum among Chinese adults aged 75 years or older in a community-based setting over10 years. METHODS: The 3,989 adults in the Kailuan Study were aged over 75 years (median age was 79 years [interquartile range: 76-82]; 2,785 normoglycaemic, 691 prediabetic and 513 diabetic, determined by fasting blood glucose levels) at baseline, predominantly male (92.9% male) and followed until December 2019. Time-varying Cox regression and competing-risk models were used to examine the hazard ratio (HR) of incident CVD and mortality across the glycaemic exposures. RESULTS: During median follow-up of 11.3 years, 433 first CVD and 2,222 deaths were recorded. Compared with normoglycaemia, multivariable-adjusted models revealed the following: (i) prediabetes was not associated with future risks for CVD (HR: 1.17; 95% CI 0.82-1.69) and all-cause mortality (HR 1.06; 95% CI 0.70-1.60); (ii) diabetes-associated enhanced risks for CVD and all-cause mortality were mainly confined to those exhibiting low-grade inflammation (high-sensitivity C-reactive protein ≥2.0 mg/L) levels. The results were consistent after multiple sensitivity analyses. CONCLUSIONS: Among a male-predominant Chinese population aged 75 years or older, compared with normoglycaemic participants, prediabetes was not associated with an enhanced 10-year CVD and all-cause mortality risk, and diabetes-associated enhanced 10-year risk was mainly confined to individuals exhibiting low-grade inflammation.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Aged , Blood Glucose/metabolism , Cardiovascular Diseases/epidemiology , China/epidemiology , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Female , Humans , Inflammation , Male , Risk FactorsABSTRACT
Soybean mosaic virus (SMV) is the most prevalent soybean viral disease in the world. As a critical enzyme in the secondary metabolism of plants, especially in lignin synthesis, cinnamyl alcohol dehydrogenase (CAD) is widely involved in plant growth and development, and in defense against pathogen infestation. Here, we performed RNAseq-based transcriptome analyses of a highly SMV-resistant accession (BYO-15) of wild soybean (Glycine soja) and a SMV-susceptible soybean cultivar (Williams 82), also sequenced together with a resistant plant and a susceptible plant of their hybrid descendants at the F3 generation at 7 and 14 days post-inoculation with SMV. We found that the expression of GsCAD1 (from G. soja) was significantly up-regulated in the wild soybean and the resistant F3 plant, while the GmCAD1 from the cultivated soybean (G. max) did not show a significant and persistent induction in the soybean cultivar and the susceptible F3 plant, suggesting that GsCAD1 might play an important role in SMV resistance. We cloned GsCAD1 and overexpressed it in the SMV-susceptible cultivar Williams 82, and we found that two independent GsCAD1-overexpression (OE) lines showed significantly enhanced SMV resistance compared with the non-transformed wild-type (WT) control. Intriguingly, the lignin contents in both OE lines were higher than the WT control. Further liquid chromatography (HPLC) analysis showed that the contents of salicylic acid (SA) were significantly more improved in the OE lines than that of the wild-type (WT), coinciding with the up-regulated expression of an SA marker gene. Finally, we observed that GsCAD1-overexpression affected the accumulation of SMV in leaves. Collectively, our results suggest that GsCAD1 enhances resistance to SMV in soybeans, most likely by affecting the contents of lignin and SA.
Subject(s)
Plant Diseases , Potyvirus , Plant Diseases/genetics , Glycine max/genetics , Salicylic Acid , Disease Resistance/geneticsABSTRACT
Animal coronaviruses (CoVs) have been identified to be the origin of Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and probably SARS-CoV-2 that cause severe to fatal diseases in humans. Variations of zoonotic coronaviruses pose potential threats to global human beings. To overcome this problem, we focused on the main protease (Mpro), which is an evolutionary conserved viral protein among different coronaviruses. The broad-spectrum anti-coronaviral drug, GC376, was repurposed to target canine coronavirus (CCoV), which causes gastrointestinal infections in dogs. We found that GC376 can efficiently block the protease activity of CCoV Mpro and can thermodynamically stabilize its folding. The structure of CCoV Mpro in complex with GC376 was subsequently determined at 2.75 Å. GC376 reacts with the catalytic residue C144 of CCoV Mpro and forms an (R)- or (S)-configuration of hemithioacetal. A structural comparison of CCoV Mpro and other animal CoV Mpros with SARS-CoV-2 Mpro revealed three important structural determinants in a substrate-binding pocket that dictate entry and release of substrates. As compared with the conserved A141 of the S1 site and P188 of the S4 site in animal coronaviral Mpros, SARS-CoV-2 Mpro contains N142 and Q189 at equivalent positions which are considered to be more catalytically compatible. Furthermore, the conserved loop with residues 46-49 in animal coronaviral Mpros has been replaced by a stable α-helix in SARS-CoV-2 Mpro. In addition, the species-specific dimerization interface also influences the catalytic efficiency of CoV Mpros. Conclusively, the structural information of this study provides mechanistic insights into the ligand binding and dimerization of CoV Mpros among different species.
Subject(s)
COVID-19 , Peptide Hydrolases , Animals , Coronavirus 3C Proteases , Dimerization , Dogs , Endopeptidases , Ligands , Peptide Hydrolases/chemistry , SARS-CoV-2ABSTRACT
In order to improve the mechanical strength and imprinting efficiency, a novel bovine serum albumin (BSA) molecularly imprinted poly(ionic liquid)/calcium alginate composite cryogel membrane (MICM) was prepared. The results of the tensile test indicated that the MICM had excellent mechanical strength which could reach up to 90.00 KPa, 30.30 times higher than the poly (ionic liquid) membrane without calcium alginate; the elongation of it could reach up to 93.70%, 8.28 times higher than the poly (ionic liquid) membrane without calcium alginate. The MICM had a very high welling ratio of 1026.56% and macropore porosity of 62.29%, which can provide effective mass transport of proteins. More remarkably, it had a very high adsorption capacity of 485.87 mg g-1 at 20 °C and 0.66 mg mL-1 of the initial concentration of BSA. Moreover, MICM also had good selective and competitive recognition toward BSA, exhibiting potential utility in protein separation. This work can provide a potential method to prepare the protein-imprinted cryogel membrane with both high mechanical strength and imprinting efficiency.
Subject(s)
Ionic Liquids , Molecular Imprinting , Cryogels , Serum Albumin, Bovine , Alginates , Molecular Imprinting/methods , AdsorptionABSTRACT
Cultivated jute, which comprises the two species Corchorus capsularis and C. olitorius, is the second most important natural fibre source after cotton. Here we describe chromosome-level assemblies of the genomes of both cultivated species. The C. capsularis and C. olitorius assemblies are each comprised of seven pseudo-chromosomes, with the C. capsularis assembly consisting of 336 Mb with 25,874 genes and the C. olitorius assembly containing 361 Mb with 28 479 genes. Although the two Corchorus genomes exhibit collinearity, the genome of C. olitorius contains 25 Mb of additional sequences than that of C. capsularis with 13 putative inversions, which might give a hint to the difference of phenotypic variants between the two cultivated jute species. Analysis of gene expression in isolated fibre tissues reveals candidate genes involved in fibre development. Our analysis of the population structures of 242 cultivars from C. capsularis and 57 cultivars from C. olitorius by whole-genome resequencing resulted in post-domestication bottlenecks occurred ~2000 years ago in these species. We identified hundreds of putative significant marker-trait associations (MTAs) controlling fibre fineness, cellulose content and lignin content of fibre by integrating data from genome-wide association studies (GWAS) with data from analyses of selective sweeps due to natural and artificial selection in these two jute species. Among them, we further validated that CcCOBRA1 and CcC4H1 regulate fibre quality in transgenic plants via improving the biosynthesis of the secondary cell wall. Our results yielded important new resources for functional genomics research and genetic improvement in jute and allied fibre crops.
Subject(s)
Corchorus , Corchorus/genetics , Genome-Wide Association Study , Genomics , Lignin , Sequence Analysis, DNAABSTRACT
Short-chain chlorinated paraffins (SCCPs), a class of ubiquitous pollutants, are considered to be embryotoxic and teratogenic. However, little is known regarding the bioactivity and mechanisms at environmentally relevant concentrations at the embryonic period. Here, a concentration-dependent reduced transcriptomic approach was used to evaluate the environmental dose (<100 ppb) effects of nine SCCP congeners and eight commercial mixtures on zebrafish embryos at 8 hpf. After 24 h of exposure, the overall biological potency of all the SCCPs, in terms of interference with 20% of the differentially expressed genes (PODDEG20), in zebrafish embryos ranged from 0.83 to 67.61 ppb. C10H14Cl8 (PODGO20 = 3.80 ppb) and C10-13 51.5% Cl (PODGO20 = 3.31 ppb) exhibited the strongest interference with biological processes compared to other SCCP homologs and mixtures, respectively. The most sensitive early molecular responses induced by SCCPs were associated with pathways of genetic damage, energy metabolite interference, and metal ion binding. Furthermore, the carbon number was positively correlated with the transcriptomic potency (PODGO20) of SCCP congeners (with chlorine content > 60%) (p = 0.038), and the chlorine content of SCCP congeners affected the bioactivity associated with genotoxic pathways. The concentration-dependent reduced transcriptomic approach significantly improved the understanding of the ecological risk of environmental contaminants at early life stages.