Gap-free genome assembly and CYP450 gene family analysis reveal the biosynthesis of anthocyanins in Scutellaria baicalensis

Scutellaria baicalensis Georgi,a member of the Lamiaceae family,is a widely utilized medicinal plant.The flavones extracted from S.baicalensis contribute to numerous health benefits,including anti-inflammatory,antiviral,and anti-tumor activities.However,the incomplete genome assembly hinders biological studies on S.baicalensis.This study presents the first telomere-to-telomere(T2T)gap-free genome assembly of S.baicalensis through the integration of Pacbio HiFi,Nanopore ultra-long and Hi-C technologies.A total of 384.59 Mb of genome size with a contig N50 of 42.44 Mb was obtained,and all sequences were anchored into nine pseudochromosomes without any gap or mismatch.In addition,we analysed the major cyanidin-and delphinidin-based anthocyanins involved in the determination of blue-purple flower using a widely-targeted metabolome approach.Based on the genome-wide identification of Cytochrome P450(CYP450)gene family,three genes(SbFBH1,2,and 5)encoding flavonoid 3′-hydroxylases(F3′Hs)and one gene(SbFBH7)encoding flavonoid 3′5′-hydroxylase(F3′5′H)were found to hydroxylate the B-ring of flavonoids.Our studies enrich the genomic information available for the Lamiaceae family and provide a toolkit for discovering CYP450 genes involved in the flavonoid decoration.

太阳能驱动的固体氧化物电解池制氢系统性能研究

采用太阳能驱动电解水制氢是实现将太阳能转换为氢能来存储的最佳方式。该文提出一种采用光伏、光热协同驱动固体氧化物电解池(SOEC)进行高温蒸汽电解的制氢系统。建立各子系统数学模型,选取北京地区夏至日气象参数,分析太阳辐照度对制氢系统的性能影响,最后对整个系统进行能量及?分析。结果表明,电流密度和温度是影响SOEC工作的重要因素。在电流密度较大的情况下升高温度,将有利于提高电解效率。耦合太阳能后系统最大能量及?效率分别达到19.1%和20.3%。?分析结果表明系统最大有用功损失发生在光电转换过程,?损比例为87%。提升光电效率,将成为提高太阳能-氢能转换效率的关键。

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis(CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination fromSeptember 2013 to September 2016 were selected for this study. The age of these patients ranged within 18-to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori(H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration.Furthermore,CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve(R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions.

Efficacy and safety of stellate ganglion block in chronic ulcerative colitis

AIM To investigate the efficacy and safety of stellate ganglion block for the treatment of patients with chronic ulcerative colitis.METHODS A total of 120 randomly selected patients with chronic ulcerative colitis treated in Cangzhou Central Hospital from January 2014 to January 2016 were included in this study. These patients were divided into two groups: control group(n = 30), patients received oral sulfasalazine treatment; experimental group(n = 90), patients received stellate ganglion block treatment. Clinical symptoms and disease activity in these two groups were compared before and after treatment using endoscopy. Blood was collected from patients on day 0, 10, 20 and 30 after treatment. Enzyme-linked immunosorbent assay was performed to determine interleukin-8(IL-8) level. The changes in IL-8 level post-treatment in the two groups were compared using repeated measures analysis of variance.RESULTS After treatment, clinical symptoms and disease activity were shown to be alleviated by endoscopy in both the control and experimental groups. However, patients in the control group did not have obvious abdominal pain relief. In addition, the degree of pain relief in the experimental group was statistically better than that in the control group(P < 0.05). Ten days after treatment, IL-8 level was found to be significantly lower in the experimental group than in the control group, and the difference was statistically significant(P < 0.05). In addition, adverse events were significantly higher in the control group than in the experimental group, and the difference was statistically significant(χ~2 = 33.215, P = 0.000).CONCLUSION The application of stellate ganglion block effectively improves treatment efficacy in chronic ulcerative colitis, relieves clinical symptoms in patients, and reduces the level of inflammatory factors. Furthermore, this approach also had a positive impact on the disease to a certain extent.

Study of the effects of nesfatin-1 on gastric function in obese rats

AIM To investigate the effects of nesfatin-1 on gastric function in obese rats. METHODS The obese rat model was induced by a high-fat diet. The gastric emptying rate and gastric acid secretory capacity of the rats were determined after treatment with different drug concentrations of nesfatin-1 and administration routes. Based on this, the expression of H+/K+-ATPase was measured using RT-PCR and western blot to preliminarily explore the mechanism of gastric acid secretion changes. RESULTS Body weight, body length, and Lee's index of the rats significantly increased in the high-fat dietinduced obese rat model. Two hours after lateral intracerebroventricular injection of nesfatin-1, the gastric emptying rate and gastric acid secretory capacity of rats decreased. Four hours after injection, both were restored to normal levels. In addition, the expression of H+/K+-ATPase decreased and moved in line with changes in gastric acid secretory capacity. Thisin vivo experiment revealed that intracerebroventricular injection of nesfatin-1, rather than intravenous injection, could suppress gastric function in obese rats. Moreover, its effect on the gastric emptying and gastric acid secretory capacity of rats is dose-dependent within a certain period of time.CONCLUSION Through this research, we provide a theoretical basis for further studies on nesfatin-1, a potential antiobesity drug.

Studies on the Renaturation with Simultaneous Purification of Recombinant Human Proinsulin with Unit of Simultaneous Renaturation and Purification of Protein in Semi-preparative Scale

The renaturation and purification of recombinant human proinsulin (rh-proinsulin) expressed in E. coli with the unit of simultaneous renaturation and purification of protein (USRPP) in semi-preparative scale was studied. The result shows that rh-proinsulin extracted with 8.0 mol/L urea can be renatured and purified simultaneously in 45 minutes with the USRPP (1050 mm ID). The purity of rh-proinsulin was found to be more than 90% and the mass recovery to be more than 80%. The renaturation effect of rh-proinsulin with the USRPP was tested by enzyme cleavage for obtaining insulin. In addition, the result was further confirmed with RPLC, SDS-PAGE electrophoresis, and MALDI-TOF, respectively.

Determination of Melamine in Quail Egg and Milk with Capillary Zone Electrophoresis

A capillary zone electrophoresis method was developed for determination of melamine in food samples, such as quail egg and milk products. The CE procedure was performed on fused silica capillary (41 cm × 75 μm I.D.) at 17 kV using pH3.1 60mmol/L phosphate buffer as run buffer and detecting at 200 nm. The proposed method showed good linearity (0.5 - 10.0 μmol/L) and low LOD (0.5 μmol/L) with good reproducibility (RSD% was 2.4 and 3.2 for migration time and peak area respectively), which made it suitable for quantity control of the related food product.

Experimental study on the improvement of insomnia model mice's symptoms by Sanwei Anmian Decoction and its disassembled prescription

Background:Insomnia is a sleep disorder,which seriously affects people's physical and mental health.Our experimental study will further explain the efficacy and mechanism of the traditional Chinese medicine prescription Sanwei Anmian Decoction as well as the single drug treatment for insomnia,and provide scientific basis for TCM decoction to cure more insomnia patients.Methods:42 mices,half male and half female,were randomly divided into 7 groups,6 in each group,Blank group,Model group,Positive group,Sanwei Anmian Decoction group(abbreviated as Sanwei group),Suanzaoren group,Maidong group,Yuanzhi group.Intraperitoneal injection(ip)of PCPA 350 mg·kg^-1 in other groups except Blank group to establish a mice model of insomnia.On the next day after the successful modeling,10ml·kg^-1 corresponding decoction was given to Sanwei group,Suanzaoren group,Yuanzhi group and Maidong group respectively,0.8mg·kg^-1 estazolam for Positive group,Blank group and the Model group with the same amount of normal saline,three times a day for two days.The body weight and the number of autonomous activities of mice were observed.The sleep rate,sleep latency and sleep time were recorded after the last administration,and the contents of serum 5-hydroxytryptamine(5-HT)and dopamine(DA)were detected.Results:The changes of hair yellowing,alarm,food loss and weight loss in mice showed that the model was successful.After the last administration,compared with the Model group and the Blank group,the weight of mice in Sanwei Anmian Decoction and each disassembled prescription group increased,the autonomous activity decreased,the number of mice fell asleep increased,the concentration of 5-HT in serum increased and the concentration of DA decreased,P<0.01,which was statistically significant.Conclusions:Sanwei Anmian Decoction can effectively improve the symptoms of PCPA insomnia mice model.For single drug,Suanzaoren Decoction has the most obvious effect on the treatment of insomnia.

Multiomics analyses of two Leonurus species illuminate leonurine biosynthesis and its evolution

The Lamiaceae family is renowned for its terpenoid-based medicinal components,but Leonurus,which has traditional medicinal uses,stands out for its alkaloid-rich composition.Leonurine,the principal active compound found in Leonurus,has demonstrated promising effects in reducing blood lipids and treating strokes.However,the biosynthetic pathway of leonurine remains largely unexplored.Here,we present the chromosome-level genome sequence assemblies of Leonurus japonicus,known for its high leonurine production,and Leonurus sibiricus,characterized by very limited leonurine production.By integrating genomics,RNA sequencing,metabolomics,and enzyme activity assay data,we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase(ADC),uridine diphosphate glucosyltransferase(UGT),and serine carboxypeptidase-like(SCPL)acyltransferase enzymes that catalyze key reactions in this pathway.Further analyses revealed that the UGT–SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L.japonicus,which contributed to the accumulation of leonurine specifically in L.japonicus.Collectively,our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.

Additive manufacturing of high-strength Inconel 718 alloy through the addition of Ti_(2) AlC MAX particles

Decreasing the content of detrimental Laves phase in additively manufactured Inconel 718 alloy is highly essential.In the present study,we introduce a novel approach to effectively suppress the precipitation of Laves phase.By ex-situ incorporation of Ti_(2) AlC MAX particles,Ti_(2) AlC/Inconel 718 composites with Ti_(2) AlC volume fractions of 5%and 10%are successfully fabricated using the directed energy deposition(DED)technique.In comparison to the Inconel 718 alloy,the 10 vol.%Ti_(2) AlC/Inconel 718 composite exhibits 70.9%higher yield strength,39.1%higher ultimate tensile strength,and 61.4%higher hardness.A detailed microstructure examination confirms that the detrimental Laves phase,which is abundantly present in the inter-dendritic region,is replaced by in-situ formed(Nb,Ti)(C,N)andγ’particles with average diam-eters of 1.12μm and 10 nm,respectively.Through non-equilibrium solidification process simulation,the suppression of Laves phase,in-situ formation of multi-scale precipitates,and the microstructural evolu-tion due to Ti_(2) AlC addition are illustrated at the mechanistic level.Conclusively,a theoretical model of Ti_(2) AlC/Inconel 718 composite is developed to reveal its underlying strengthening mechanism.It is indi-cated that Ti_(2) AlC/Inconel 718 composites possess the capability to be a next-generation high-end nickel-based alloy.

Whether Warfarin Therapy is Associated with Damage on Renal Function in Chinese Patients with Nonvalvular Atrial Fibrillation

Background： Warfarin is the most common oral anticoagulant to decrease the stroke risk associated with atrial fibrillation （AF）. There are very few prospective studies that have explored whether warfarin has an association with damage on renal function in Chinese patients with nonvalvular AF （NVAF）. The aim of this study was to evaluate the effects of warfarin on renal function and study the factors associated with kidney dysfunction in Chinese adult NVAF patients without dialysis therapy. Methods： From January 2011 to December 2013, a total of 951 NVAF patients from 18 hospitals were enrolled. The estimated glomerular filtration rate （eGFR） was calculated from baseline and fbllow-up serum creatinine levels. Kaplan-Meier survival curves compared the survival of a 〉25% decline in eGFR （hereafter, endpoint）~ while Cox models estimated hazard ratios （HRs） and 95% confidence intervals for this event after adjustment for age, gender, and selected potential risk factors for renal dysfunction. Cox regression analysis of the various clinical potential variables was performed to identify the predictors of a -〉25% decline in eGFR. Results： After a 58-month follow-up, 951 NVAF patients were divided by observation into warfarin （n = 655） and no anticoagulation groups （n = 296） and 120 （12.6%） patients experienced renal endpoint. Kaplan-Meier survival curves showed that the survival period was not different in the two groups （χ2 = 0.178, log-rank P = 0.67）, but patients with systolic blood pressure （SBP） 〈140 mmHg have significant difference with patients with SBP ≥140 mmHg （χ2 = 4.903, log-rank P = 0.03）. Multivariate Cox regression analysis revealed baseline eGFR and SBP as independent predictors of the endpoint, with HRs of 1.00, and 1.02, respectively. Conclusion： In patients with NVAF, eGFR and SBP are associated with the deterioration of kidney function while Warfarin is not the risk factor of the ≥25% decline in eGFR.

A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants

The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years.The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants.Here we show that the bivalency of an affinity maturated fully human singledomain antibody(n3113.1-Fc)exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus,and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2(ACE2)humanized mice.The crystal structure of n3113 in complex with the receptor-binding domain(RBD)of SARS-CoV-2,combined with the cryo-EM structures of n3113 and spike ecto-domain,reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2.The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion,expanding our recognition of neutralization by antibodies against SARS-CoV-2.Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages,including Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1),and Delta(B.1.617.2)for n3113.1-Fc with Y58L mutation,demonstrating the potential of n3113.1-Fc(Y58L)as a promising candidate for clinical development to treat COVID-19.

Deregulation of tumor suppressive ASXL1−PTEN/AKT axis in myeloid malignancies

Mutations of epigenetic regulators are pervasive in human tumors.ASXL1 is frequently mutated in myeloid malignancies.We previously found that ASXL1 forms together with BAP1 a complex that can deubiquitinylate mono-ubiquitinylated lysine 119 on histone H2A(H2AK119ub1),a Polycomb repressive mark.However,a complete mechanistic understanding of ASXL1 in transcriptional regulation and tumor suppression remains to be defined.Here,we find that depletion of Asxl1 confers murine 32D cells to IL3-independent growth at least partly due to sustained activation of PI3K/AKT signaling.Consistently,Asxl1 is critical for the transcriptional activation of Pten,a key negative regulator of AKT activity.Then we confirm that Asxl1 is specifically enriched and required for H2AK119 deubiquitylation at the Pten promoter.Interestingly,ASXL1 and PTEN expression levels are positively correlated in human blood cells and ASXL1 mutations are associated with lower expression levels of PTEN in human myeloid malignancies.Furthermore,malignant cells with ASXL1 downregulation or mutations exhibit higher sensitivity to the AKT inhibitor MK2206.Collectively,this study has linked the PTEN/AKT signaling axis to deregulated epigenetic changes in myeloid malignancies.It also provides a rationale for mechanism-based therapy for patients with ASXL1 mutations.