Lactic acid induced defense responses in tobacco against Phytophthora nicotianae.

Induced resistance is considered an eco-friendly disease control strategy, which can enhance plant disease resistance by inducing the plant's immune system to activate the defense response. In recent years, studies have shown that lactic acid can play a role in plant defense against biological stress; however, whether lactic acid can improve tobacco resistance to Phytophthora nicotianae, and its molecular mechanism remains unclear. In our study, the mycelial growth and sporangium production of P. nicotianae were inhibited by lactic acid in vitro in a dose-dependent manner. Application of lactic acid could reduce the disease index, and the contents of total phenol, salicylic acid (SA), jasmonic acid (JA), lignin and H2O2, catalase (CAT) and phenylalanine ammonia-lyase (PAL) activities were significantly increased. To explore this lactic acid-induced protective mechanism for tobacco disease resistance, RNA-Seq analysis was used. Lactic acid enhances tobacco disease resistance by activating Ca2+, reactive oxygen species (ROS) signal transduction, regulating antioxidant enzymes, SA, JA, abscisic acid (ABA) and indole-3-acetic acid (IAA) signaling pathways, and up-regulating flavonoid biosynthesis-related genes. This study demonstrated that lactic acid might play a role in inducing resistance to tobacco black shank disease; the mechanism by which lactic acid induces disease resistance includes direct antifungal activity and inducing the host to produce direct and primed defenses. In conclusion, this study provided a theoretical basis for lactic acid-induced resistance and a new perspective for preventing and treating tobacco black shank disease.

Topological Electronic Transition Contributing to Improved Thermoelectric Performance in p-Type Mg3Sb2- xBix Solid Solutions.

Topological electronic transition is the very promising strategy for achieving high band degeneracy (NV) and for optimizing thermoelectric performance. Herein, this work verifies in p-type Mg3Sb2- xBix that topological electronic transition could be the key mechanism responsible for elevating the NV of valence band edge from 1 to 6, leading to much improved thermoelectric performance. Through comprehensive spectroscopy characterizations and theoretical calculations of electronic structures, the topological electronic transition from trivial semiconductor is unambiguously demonstrated to topological semimetal of Mg3Sb2- xBix with increasing the Bi content, due to the strong spin-orbit coupling of Bi and the band inversion. The distinct evolution of Fermi surface configuration and the multivalley valence band edge with NV of 6 are discovered in the Bi-rich compositions, while a peculiar two-step band inversion is revealed for the first time in the end compound Mg3Bi2. As a result, the optimal p-type Mg3Sb0.5Bi1.5 simultaneously obtains a positive bandgap and high NV of 6, and thus acquires the largest thermoelectric power factor of 3.54 and 6.93 µW cm-1 K-2 at 300 and 575 K, respectively, outperforming the values in other compositions. This work provides important guidance on improving thermoelectric performance of p-type Mg3Sb2- xBix utilizing the topological electronic transition.

Enhancing the carbon content of coal gangue for composting through sludge amendment: A feasibility study.

Cocomposting coal gangue and sludge eliminates the challenge of utilizing coal gangue. However, there is limited understanding about the feasibility of cocomposting sludge and coal gangue, as well as the composting indicators, functional microorganisms, and safety risks involved. Therefore, this study evaluated the feasibility of enhancing carbon composting in coal gangue by incorporating sludge along with sawdust as a conditioner. Three laboratory-scale reactors were designed and labeled as T1 (20 % coal gangue, 60 % sludge, and 20 % sawdust), T2 (40 % coal gangue, 40 % sludge, and 20 % sawdust), and T3 (60 % coal gangue, 20 % sludge, and 20 % sawdust). Seed germination and plant growth assessments were conducted to ensure compost stability and assess phytotoxicity to cabbage (Brassica rapa chinensis L.) in terms of growth and biomass. The results indicated that the temperature, pH, EC and ammonia nitrogen of all three reactor conditions met the requirements for product decomposition. Composting was successfully achieved when the sludge proportion was 20 % (T3). However, when the sludge proportion was markedly high (T1), the harmlessness of the compost was reduced. The germination indices of T1, T2, and T3 reached 95 %, 122 %, and 119 % at maturity, respectively. This confirmed that the harmless cycle, which involved promoting condensation and aromatization, enhancing decay, and reducing composting time, was shorter in T2 and T3 than in T1. Coal gangue can also serve as a beneficial habitat for microorganisms, promoting an increase in their population and activity. Potting experiments in sandy soil revealed that the mechanism of action of compost products in soil included not only the enhancement of soil nutrients but also the improvement of soil texture. The results of this study suggest that using coal gangue as a raw material for composting is an efficient and environmentally friendly approach for producing organic fertilizers.

A time-course transcriptome analysis revealing the potential molecular mechanism of early gonadal differentiation in the Chinese giant salamander.

The Chinese giant salamander (CGS) Andrias davidianus is the largest extant amphibian and has recently become an important species for aquaculture with high economic value. Meanwhile, its wild populations and diversity are in urgent need of protection. Exploring the mechanism of its early gonadal differentiation will contribute to the development of CGS aquaculture and the recovery of its wild population. In this study, transcriptomic and phenotypic research was conducted on the critical time points of early gonadal differentiation of CGS. The results indicate that around 210 days post-hatching (dph) is the critical window for female CGS's gonadal differentiation, while 270 dph is that of male CGS. Besides, the TRPM1 gene may be the crucial gene among many candidates determining the sex of CGS. More importantly, in our study, key genes involved in CGS's gonadal differentiation and development are identified and their potential pathways and regulatory models at early stage are outlined. This is an initial exploration of the molecular mechanisms of CGS's early gonadal differentiation at multiple time points, providing essential theoretical foundations for its captive breeding and offering unique insights into the conservation of genetic diversity in wild populations from the perspective of sex development.

Glycine max acyl-acyl carrier protein thioesterase B gene overexpression alters lipid content and fatty acid profile of Arabidopsis seeds.

The fatty acyl-acyl carrier protein thioesterase B (FATB ) gene, involved in the synthesis of saturated fatty acids, plays an important role in the content of fatty acid and composition of seed storage lipids. However, the role of FATB in soybeans (Glycine max ) has been poorly characterised. This paper presents a preliminary bioinformatics and molecular biological investigation of 10 hypothetical FATB members. The results revealed that GmFATB1B , GmFATB2A and GmFATB2B contain many response elements involved in defense and stress responses and meristem tissue expression. Moreover, the coding sequences of GmFATB1A and GmFATB1B were significantly longer than those of the other genes. Their expression varied in different organs of soybean plants during growth, with GmFATB2A and GmFATB2B showing higher relative expression. In addition, subcellular localisation analysis revealed that they were mainly present in chloroplasts. Overexpression of GmFATB1A , GmFATB1B , GmFATB2A and GmFATB2B in transgenic Arabidopsis thaliana plants increased the seed oil content by 10.3%, 12.5%, 7.5% and 8.4%, respectively, compared to that in the wild-type and led to significant increases in palmitic and stearic acid content. Thus, this research has increased our understanding of the FATB family in soybeans and provides a theoretical basis for subsequent improvements in soybean quality.

Comparison between an SGLT2 inhibitor and insulin in tumor-to-tissue contrasts in 18F-FDG PET imaging of diabetic mice.

18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has been widely utilized for tumor diagnosis. Hyperglycemia affects the 18F-FDG uptake and reduces tumor-to-tissue contrasts, however, ideal hypoglycemic drugs are lacking. This study compared the role of insulin with the novel widely used hypoglycemic drug, sodium-glucose cotransporter 2 (SGLT2) inhibitor, on 18F-FDG PET imaging in diabetic conditions. The streptozotocin (STZ)-induced diabetic C57BL/6N mice were inoculated with B16 (mouse melanoma) cells to establish the xenograft tumor model. After the mice had been administrated with dapagliflozin (30 mg/kg, IG) or insulin (0.75 U/kg, IP) for one hour, 9.25 MBq/10 g 18F-FDG was injected. Biodistributions were detected by gamma counting and microPET imaging. The results showed dapagliflozin did not significantly affect the 18F-FDG uptake in tumors but reduced uptake in reference tissues, resulting in a significant increase in the tumor-to-skeletal muscle ratio. Conversely, insulin increased 18F-FDG uptake in tumors without significant reduction in uptake in reference tissues; Although there was an observable improvement in tumor imaging, it did not reach significantly statistical differences. This study suggests that insulin and SGLT2 inhibitor yield comparable effects on the quality of 18F-FDG PET imaging in diabetic patients. Nevertheless, SGLT2 inhibitors would be more suitable when skeletal muscle is used as reference tissue.

Overexpressing GmCGS2 Improves Total Amino Acid and Protein Content in Soybean Seed.

Soybean (Glycine max (L.) Merr.) is an important source of plant protein, the nutritional quality of which is considerably affected by the content of the sulfur-containing amino acid, methionine (Met). To improve the quality of soybean protein and increase the Met content in seeds, soybean cystathionine γ-synthase 2 (GmCGS2), the first unique enzyme in Met biosynthesis, was overexpressed in the soybean cultivar "Jack", producing three transgenic lines (OE3, OE4, and OE10). We detected a considerable increase in the content of free Met and other free amino acids in the developing seeds of the three transgenic lines at the 15th and 75th days after flowering (15D and 75D). In addition, transcriptome analysis showed that the expression of genes related to Met biosynthesis from the aspartate-family pathway and S-methyl Met cycle was promoted in developing green seeds of OE10. Ultimately, the accumulation of total amino acids and soluble proteins in transgenic mature seeds was promoted. Altogether, these results indicated that GmCGS2 plays an important role in Met biosynthesis, by providing a basis for improving the nutritional quality of soybean seeds.

Remediation of Pb(II) and Cd(II) in polluted waters with calcium thioglycolate-modified straw biochar.

The pollution of water bodies by heavy metals (HMs) such as Pb(II) and Cd(II) poses a serious environmental risk. Herein, rice straw biochar (RBC) modified with calcium thioglycolate was used to remove Pb(II) and Cd(II) from aqueous solutions. The adsorption performance of the modified biochar was investigated via adsorption kinetics and isotherm model fitting. Furthermore, scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were used to elucidate the modification and adsorption mechanisms. The results showed that the modification process loaded sulfur-containing functional groups, calcium carbonate, and calcium oxalate crystals on the biochar surface, considerably enhancing its complexation performance and ion-exchange capacity. The equilibrium adsorption amounts for Pb(II) and Cd(II) reached 124.92 and 65.44 mg g-1 in unary systems, respectively; they reached 121.34 and 39.43 mg g-1 in a binary Pb(II) and Cd(II), respectively. Moreover, the optimal adsorption conditions were as follows: pH = 6, temperature = 25 °C, dosage = 0.8 g L-1, and contact time = 2 h. In the binary Pb(II) and Cd(II) system, the adsorption process obeyed the Langmuir competitive adsorption model, which means that one adsorption site on the modified biochar was effective for only one heavy-metal ion, and the modified biochar was more selective for Pb(II) than for Cd(II). The adsorption mechanism, which was dominated by chemisorption, mainly involved complexation, precipitation, ion exchange, and cation-π interactions. Meanwhile, adsorption and desorption experiments indicated that the modified biochar exhibited satisfactory recycling performance, demonstrating its feasibility as an inexpensive and efficient heavy-metal adsorbent for polluted water.

Pregnancy-related low back/pelvic girdle pain: Prevalence, severity, and risk factors in Zhengzhou, China.

BACKGROUND: Pregnancy-related low back pain (LBP) and pelvic girdle pain (PGP) significantly affect the quality of life of pregnant women. Understanding their severity and risk factors may help prevent and alleviate such pain and their resulting dysfunction. OBJECTIVE: This study investigated the prevalence, severity, and biopsychosocial risk factors of pregnancy-related LBP and PGP in Zhengzhou, China. METHODS: The Numeric Pain Rating Scale (NPRS), Chinese version of the Roland-Morris Disability Questionnaire (RMDQ), and other questionnaires were self-administered by 1020 pregnant women undergoing treatment at a tertiary hospital between July and December 2019. Binary logistic regression was used to identify factors associated with pregnancy-related LBP and/or PGP. RESULTS: The prevalence of LBP and/or PGP during pregnancy was 63.0%, and most participants (80.4%) had both. The mean NPRS and RMDQ disability scores were 2.44 ± 2.10 and 6.66 ± 4.65, respectively. A higher gestational body mass index, LBP and/or PGP during menstruation, history of pregnancy-related LBP and/or PGP, and constant pressure were significantly associated with pregnancy-related LBP and/or PGP. Subjective support was a protective factor against LBP and/or PGP. CONCLUSION: The prevalence of LBP and/or PGP was high. The risk factors should be included in routine prenatal care to identify patients at risk of LBP and/or PGP.

Global, regional, and national burden of chronic respiratory diseases and associated risk factors, 1990-2019: Results from the Global Burden of Disease Study 2019.

Background: The burden of chronic respiratory diseases has changed over the three decades. This study aims to describe the spatiotemporal trends of prevalence, mortality, and disability-adjusted life years (DALY) due to chronic respiratory diseases (CRDs) worldwide during 1990-2019 using data from the Global Burden of Disease Study 2019 (GBD 2019). Methods: The prevalence, mortality, and DALY attributable to CRDs and risk factors from 1990 to 2019 were estimated. We also assessed the driving factors and potentiality for improvement with decomposition and frontier analyses, respectively. Results: In 2019, 454.56 [95% uncertainty interval (UI): 417.35-499.14] million individuals worldwide had a CRD, showing a 39·8% increase compared with 1990. Deaths due to CRDs were 3.97 (95%UI: 3.58-4.30) million, and DALY in 2019 was 103.53 (95%UI: 94.79-112.27) million. Declines by average annual percent change (AAPC) were observed in age-standardized prevalence rates (ASPR) (0.64% decrease), age-standardized mortality rates (ASMR) (1.92%), and age-standardized DALY rates (ASDR) (1.72%) globally and in 5 socio-demographic index (SDI) regions. Decomposition analyses represented that the increase in overall CRDs DALY was driven by aging and population growth. However, chronic obstructive pulmonary disease (COPD) was the leading driver of increased DALY worldwide. Frontier analyses witnessed significant improvement opportunities at all levels of the development spectrum. Smoking remained a leading risk factor (RF) for mortality and DALY, although it showed a downward trend. Air pollution, a growing factor especially in relatively low SDI regions, deserves our attention. Conclusion: Our study clarified that CRDs remain the leading causes of prevalence, mortality, and DALY worldwide, with growth in absolute numbers but declines in several age-standardized estimators since 1990. The estimated contribution of risk factors to mortality and DALY demands the need for urgent measures to improve them. Systematic review registration: http://ghdx.healthdata.org/gbd-results-tool.

Platelet and ferritin as early predictive factors for the development of macrophage activation syndrome in children with Kawasaki disease: A retrospective case-control study.

Objective: To investigate the early predictive factors for Kawasaki disease complicated with macrophage activation syndrome (KD-MAS). Methods: We performed a retrospective case-control study in children with KD from August 2017 to August 2022, involving 28 cases with KD-MAS and 112 cases not developing KD-MAS. Based on the univariate analysis, binary logistic regression was used to identify the early predictive factors for KD-MAS development, and the receiver operating characteristic curve (ROC) analysis was carried out to obtain the optimal cut-off value. Results: Two predictive factors were associated with the development of KD-MAS, which were PLT (OR = 1.013, 95%CI, 1.001-1.026), and serum ferritin (OR = 0.991, 95%CI, 0.982-0.999). The cut-off value of PLT was 110 × 109/L, and the cut-off value of serum ferritin was 548.4 ng/ml. Conclusion: Children with KD who had a PLT count under 110 × 109/L, and a serum ferritin level over 548.4 ng/ml are more likely to develop KD-MAS.

Genome-wide identification and expression analysis of diacylglycerol acyltransferase genes in soybean (Glycine max).

Background: Soybean (Glycine max) is a major protein and vegetable oil source. In plants, diacylglycerol acyltransferase (DGAT) can exert strong flux control, which is rate-limiting for triacylglycerol biosynthesis in seed oil formation. Methods: Here, we identified soybean DGAT genes via a bioinformatics method, thereby laying a solid foundation for further research on their function. Based on our bioinformatics analyses, including gene structure, protein domain characteristics, and phylogenetic analysis, 26 DGAT putative gene family members unevenly distributed on 12 of the 20 soybean chromosomes were identified and divided into the following four groups: DGAT1, DGAT2, WS/DGAT, and cytoplasmic DGAT. Results: The Ka/Ks ratio of most of these genes indicated a significant positive selection pressure. DGAT genes exhibited characteristic expression patterns in soybean tissues. The differences in the structure and expression of soybean DGAT genes revealed the diversity of their functions and the complexity of soybean fatty acid metabolism. Our findings provide important information for research on the fatty acid metabolism pathway in soybean. Furthermore, our results will help identify candidate genes for potential fatty acid-profile modifications to improve soybean seed oil content. Conclusions: This is the first time that in silico studies have been used to report the genomic and proteomic characteristics of DGAT in soybean and the effect of its specific expression on organs, age, and stages.

Analysis of oil synthesis pathway in Cyperus esculentus tubers and identification of oleosin and caleosin genes.

The tubers of the widely distributed Cyperus esculentus are rich in oil, and therefore, the plant is considered to have a high utilization value in the vegetable oil industry. Oleosins and caleosins are lipid-associated proteins found in oil bodies of seeds; however oleosins and caleosins genes have not been identified in C. esculentus. In this study, we performed transcriptome sequencing and lipid metabolome analysis of C. esculentus tubers at four developmental stages to obtain the information on their genetic profile, expression trends, and metabolites in oil accumulation pathways. Overall, 120,881 non-redundant unigenes and 255 lipids were detected; 18 genes belonged to the acetyl-CoA carboxylase (ACC), malonyl-CoA:ACP transacylase (MCAT), ß-ketoacyl-ACP synthase (KAS), and fatty acyl-ACP thioesterase (FAT) gene families involved in fatty acid biosynthesis, and 16 genes belonged to the glycerol-3-phosphate acyltransferase (GPAT), diacylglycerol acyltransferase 3 (DGAT3), phospholipid:diacylglycerol acyltransferase (PDAT), FAD2, and lysophosphatidic acid acyltransferase (LPAAT) gene families playing important roles in triacylglycerol synthesis. We also identified 9 oleosin- and 21 caleosin-encoding genes in C. esculentus tubers. These results provide detailed information on the C. esculentus transcriptional and metabolic profiles, which can be used as reference for the development of strategies to increase oil content in C. esculentus tubers.

Utilization of KOH-modified fly ash for elimination from aqueous solutions of potentially toxic metal ions.

Long-term accumulation of toxic heavy metals in the environment was a potential hidden danger. High energy consumption, complicated operation and low adsorption capacity were the disadvantages of most current adsorbents. This study used one-step modification of fly ash (FA) by low-temperature melting method with KOH as the activator to generate modified fly ash (KFA) with high adsorption capacity to remove heavy metals from aqueous solutions. Various characterization results revealed a destruction that occurred on the surface structure of adsorbent, 12 times increase in specific surface area, and metal ions were successfully adsorbed onto KFA surface. Furthermore, adsorption proceeded most favorably at pH of 5, the presence of ionic strength and co-existing cations significantly influenced the adsorption effects. The description of adsorption data was more suitable by pseudo-second-order kinetics and Langmuir isotherm models. And in single system at 25 °C, for Pb(II), Cu(II), and Cd (II), the qm were 337.41, 310.09 and 125.00 mg·g-1. However, in ternary system, the qm decreased for all three ions in the order Pb(II) > Cu(II) > Cd(II), which was different from the law in single system, and the Pb(II) adsorption was found to have a significant inhibited effect on adsorption of Cd(II) and Cu(II). The adsorption mechanisms including ion exchange, electrostatic attraction and complexation were revealed. And by exploring the bioaccessibility of absorbed heavy metals in four simulated digestive fluids, it was found that KFA could load heavy metal ions and enable their release in organisms and other aquatic environments, which provided the possibility for subsequent related studies. Therefore, KFA with low energy consumption and high adsorption capacity is equipped a prospective development space on removing heavy metals from wastewater.

The role of available nitrogen in the adsorption of polystyrene nanoplastics on magnetic materials.

Several studies have been conducted on nanoplastics (NPs). However, few studies have investigated the complexity of the interactions between NPs and other aqueous pollutants in multi-solute media. In this study, the adsorption of polystyrene nanoplastics (PSNPs) on magnetic materials (MS) in the presence of available nitrogen (AN) was studied. The results demonstrated that the adsorbed amount of PSNPs increased in the presence of ammonium nitrogen (NH4+-N), whereas no significant difference was detected on the adsorbed amount of PSNPs using nitrate nitrogen (NO3--N) as a cosolute. The increase in the adsorbed amount of PSNPs was attributed to the formation of an MS-PSNPs-NH4+-N complex. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and zeta potential analyses indicated that the PSNPs with NH4+-N as a cosolute can be bound on the MS surfaces. Moreover, the change in the PSNPs amount adsorbed by MS depends on the valence state, electronegativity of the coexisting ions, and the surface properties and functional groups of PSNPs. Additionally, the ionic strength, dissolved organic matter, solution pH, metal cations and the subsequent release of MS-coated PSNPs and NH4+-N changed considerably in different aquatic systems and artificial nitrating fluids. Among different natural aquatic systems, the PSNPs adsorption on MS was excellent in lake water. The results indicate high potential for the attachment of PSNPs to MS in the presence of AN and further deepen the understanding of removing NPs using magnetic materials in aqueous systems with various coexisting contaminants.

Early monitoring of parasitism by Aphidiinae parasitoids on the grain aphid Sitobion miscanthi in wheat fields using DNA barcoding.

BACKGROUND: Sitobion miscanthi is a major wheat pest at the grain-filling stage found in China. Identifying parasitoid species and understanding parasitism rates are keys to controlling the aphids via natural enemies in the wheat field. RESULTS: In the present study, a method based on DNA barcoding for early determination of the community composition of Aphidiinae parasitoids and parasitism on the aphid was developed. The proposed method detected Aphidius gifuensis as the predominant parasite, with parasitism rates of 40.1 ± 2.8% in 2019 and 65.7 ± 3.7% in 2022, and found that the rate varied significantly among different wheat varieties. COI primers efficiently amplified the Aphidiinae parasitoids COI fragments and amplified the aphid COI fragments derived from parasitized (mummified) S. miscanthi. Thus, the COI barcode is not sufficiently specific to unambiguously detect immature parasitoids inside their S. miscanthi hosts. However, it can be used to detect the DNA extracted from mummified aphids. In contrast, the 16S and LWRh primers effectively amplified and identified the parasitoids in parasitized aphids. The 16S primer was reliable even in the early stages of parasitism (24 h) and for DNA samples stored at -20 °C for 5 days. The three barcodes from COI, 16S, and LWRh genes could not clearly distinguish a few certain Aphidiinae species owing to relatively low intraspecific and interspecific diversity. CONCLUSION: The morphological features remain indispensable when identifying Aphidiinae species. Nonetheless, the COI and 16S primers could be used in combination for monitoring the parasitism rates on S. miscanthi in wheat fields. © 2022 Society of Chemical Industry.

Identification of a novel TNNI3 synonymous variant causing intron retention in autosomal recessive dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy type 2A (DCM2A, MIM: #611880) is a rare autosomal recessive heart disease leading to heart failure and sudden cardiac death. However, the causative role of TNNI3 in DCM2A is still questioned due to few cases reported and the conflicting molecular biological evidence. METHODS: Trio whole-exome sequencing (trio-WES) was performed in a Chinese family with dilated cardiomyopathy. Sanger sequencing and real-time quantitative PCR were used to confirm the variants identified. Expression outcome caused by the synonymous mutation was validated by minigene splicing analyses. RESULTS: The one-year-old girl presented severe left ventricular enlargement and significantly reduced left ventricular systolic function and she died of respiratory and heart failure soon after her diagnosis. Trio-WES revealed a compound heterozygous variants of TNNI3, a novel c.24G＞A (p.Ala8Ala) (NM_000363.4) in exon 2 and a deletion of entire gene. Minigene splicing analyses showed it led to an intron retention (c.24 + 1_24 + 45ins) by intron 2 cryptic splicing. CONCLUSIONS: Our study describes and characterizes a synonymous mutation in TNNI3 gene, supporting the clinical diagnosis of an autosomal recessive DCM. Our study emphasizes the importance of functional analysis to assess the potential pathogenicity of synonymous mutations, especially when the synonymous variants are not annotated as benign.

Oxyberberrubine, a novel liver microsomes-mediated secondary metabolite of berberine, alleviates hyperuricemic nephropathy in mice.

BACKGROUND: Berberrubine (BRB), one of the major metabolites of berberine (BBR), exerts an anti-hyperuricemic effect even superior to BBR. Liver is an important location for drug transformation. Nevertheless, there are few studies on the bioactivities and metabolites of BRB. PURPOSE: We investigated whether oxyberberrubine (OBR), a liver metabolite of BRB, exerted urate-lowering and reno-protective effects in hyperuricemic mice. METHODS: Liver microsomes were used to incubate BRB for studying its biotransformation. We isolated and identified its new metabolite OBR, and investigated its anti-hyperuricemic and reno-protective effects. In this work, the hyperuricemic mice model was established by receiving potassium oxonate (PO) and hypoxanthine (HX) for 7 consecutive days. 1 h after modeling, different dosages of OBR (5, 10 and 20 mg/kg), BRB (20 mg/kg) or febuxostat (Fex, 5 mg/kg) were given mice by gavage. RESULTS: Results showed that OBR possessed potent anti-hyperuricemic and reno-protective effects in hyperuricemic mice. Serum uric acid (UA) level was lowered, and the activities of xanthine oxidase (XOD) as well as adenosine deaminase (ADA) in the liver were suppressed after treatment with OBR. Hepatic expressions of XOD were remarkably decreased at mRNA and protein levels by OBR treatment. In addition, OBR prominently alleviated renal injury, embodied in markedly reduced serum creatinine and blood urea nitrogen (BUN) levels, decreased inflammatory mediators (TNF-α, IL-1ß, IL-6 and IL-18) levels, mRNA expression of CYP27B1 and repairment of renal tissues damage. Besides, OBR down-regulated renal expression of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 at mRNA and protein levels. CONCLUSIONS: In short, our study indicated that OBR possessed superior anti-hyperuricemic and reno-protective effects, at least in part, through the inhibition of XOD, URAT1, GLUT9 and NLRP3 inflammasome signaling pathway in the kidney.

The GRACE risk score predicts no-reflow and MACE in patients with STEMI undergoing PCI / 西安交通大学学报(医学版)

【Objective】 Coronary no-reflow during percutaneous conranary intervention (PCI) often results in the failure of ischemic myocardial reperfusion and major adverse cardiovascular events (MACE). The present study sought to evaluate whether the GRACE risk score can predict coronary no-reflow in STEMI patients undergoing PCI. 【Methods】 We consecutively recruited 1 118 patients with STEMI who were admitted to Gansu Provincial People’s Hospital and The First Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2011. Main demographic data, cardiovascular risk factors, blood lipid and other biochemical indicators were recorded. Coronary angiography was performed by a radial artery approach using the standard Judkins technique. Coronary no-reflow was evaluated by at least two independent experienced cardiologists. The GRACE risk score was calculated with a computer program. All the cases were followed up by medical records, face-to-face interviews or telephone calls. Finally, we analyzed the predictive value of the GRACE risk score for coronary non-reflow and MACE in STEMI patients undergoing PCI. 【Results】 During a median period of 36 months, 58 of the 1 118 patients (5.2%) were lost to follow-up. Of the remaining 1 060 patients, 118 (11.1%) had no-reflow and 147 (13.9%) had MACE. The GRACE score was higher in patients with no-reflow than those without no-reflow. Multivariate logistic regression established that the GRACE score was an independent predictor for coronary no-reflow (OR=1.034; P=0.002). And multivariate Cox analysis showed the GRACE score was an independent predictor of MACE. The area under the ROC curve for coronary no-reflow and MACE was 0.719 and 0.697, respectively. Kaplan-Meier analysis showed that the probability of rehospitalization for heart failure, reinfarction, all-cause death and cumulative cardiovascular events increased with the increase of the GRACE risk score. 【Conclusion】 The GRACE risk score is a readily available predictive scoring system for coronary no-reflow and MACE in STEMI patients.

Optimization of labeling methods for a novel prostate cancer PET probe Al 18F-PSMA-137 / 中华核医学与分子影像杂志

Objective:To investigate the effects of different labeling conditions on the yield of Al 18F-labeled 1, 4, 7-triazacylononane-1, 4, 7-triaceticacid (NOTA)-prostate specific membrane antigen (PSMA)-137, and to determine the experimental condition for obtaining Al 18F-PSMA-137 probe in high yield. Methods:The effects of different pH values, buffer systems (acetic acid-sodium acetate buffer system and potassium hydrogen phthalate (KHP) buffer system), AlCl 3-ligand ratios, ligand amounts, ethanol volumes and reaction temperatures on the labeling rate were investigated in detail. Results:The pH value of the reaction solution had a significant effect on the labeling rate, and the optimal range was 4.0-4.5. When the pH value was higher than 4.5, the labeling rate decreased significantly. Both the acetic acid-sodium acetate buffer system and the KHP buffer system could be used to label NOTA-PSMA-137 with Al 18F, and the KHP buffer system obtained higher labeling rate. The ratio of AlCl 3-ligand affected the labeling rate, and the highest labeling rate could be obtained when the ratio of AlCl 3-ligand was 0.54-0.62. When the ratio of AlCl 3-ligand was fixed, increasing the amount of ligand could improve the labeling yield. Adding hydrophilic organic solvent ethanol to the reaction system could significantly increase yield, with the highest labeling rate being achieved at a volume of 100 μl ethanol. The most suitable reaction temperature was 100 ℃, and when the temperature raised to 110 ℃, the labeling rate decreased significantly. The most suitable labeling conditions for NOTA-PSMA-137 were as following: 25 μl KHP buffer (0.50 mol/L, pH=4.0), 7.0 μl AlCl 3 solution (20 mmol/L), 200 μl Na 18F solution (74-80 MBq) and 230 μg ligand NOTA-PSMA-137 were mixed in a vial, then stood for 5 min and 100 μl ethanol was added, and all reagents were heated at 100 ℃ for 10 min. The yield of Al 18F-PSMA-137 under above conditions were 85.7%-88.5%. Conclusion:Optimization of labeling condition can improve the yield of Al 18F-PSMA-137 and the stability of the labeling.