Arabidopsis thaliana is an important and long-established model species for plant molec-ular biology,genetics,epigenetics,and genomics.However,the latest version of reference genome still contains a significant number of missing segments.Here,we reported a high-quality and almost complete Col-0 genome assembly with two gaps(named Col-XJTU)by combining the Oxford Nanopore Technologies ultra-long reads,Pacific Biosciences high-fidelity long reads,and Hi-C data.The total genome assembly size is 133,725,193 bp,introducing 14.6 Mb of novel sequences compared to the TAIR1 0.1 reference genome.All five chromosomes of the Col-XJTU assembly are highly accurate with consensus quality(QV)scores＞60(ranging from 62 to 68),which are higher than those of the TAIR10.1 reference(ranging from 45 to 52).We completely resolved chro-mosome(Chr)3 and Chr5 in a telomere-to-telomere manner.Chr4 was completely resolved except the nucleolar organizing regions,which comprise long repetitive DNA fragments.The Chr1 cen-tromere(CEN1),reportedly around 9 Mb in length,is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats.Using the cutting-edge sequencing data and novel computational approaches,we assembled a 3.8-Mb-long CEN1 and a 3.5-Mb-long CEN2.We also investigated the structure and epigenetics of centromeres.Four clusters of CEN180 monomers were detected,and the centromere-specific histone H3-like protein(CENH3)exhibited a strong preference for CEN 180 Cluster 3.Moreover,we observed hypomethylation patterns in CENH3-enriched regions.We believe that this high-quality genome assembly,Col-XJTU,would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms,as well as the genetic and epigenetic features in plants.

Complex structural variants(CSVs)are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants.How-ever,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy.As a result,there has been limited progress for CSV discovery com-pared with simple structural variants.Here,we systematically analyzed the multi-breakpoint con-nection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read sequencing.Specifically,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined models.Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms.Notably,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70％,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,respectively.Moreover,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed duplication.Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs.Mako is publicly available at https://github.com/xjtu-omics/Mako.

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG). METHODS: A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment. RESULTS: After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05). CONCLUSIONS Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.
Activities of Daily Living ; Child ; Humans ; Immunosuppressive Agents ; Myasthenia Gravis ; drug therapy ; Neoplasm Recurrence, Local ; Tacrolimus ; therapeutic use

Two previously undescribed steroidal compounds, 16, 23-epoxy-22, 26-epimino-cholest-22(N), 23, 25(26)-trien-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside (1) and 26-O-β-D-glucopyranosyl-(25R)-5α-furost-20(22)-en-3β, 26-diol (2), together with 7 known ones including 26-O-β-D-glucopyranosyl-(25R)-5, 20(22)-dien-furost-3β, 26-diol (3), (25R)-5-en-spirost-3β-ol-O-β-D-glucopyranosyl-(1→4)-[α-L-rhmanopyranosyl-(1→2)]-β-D-galactopyranoside (4), funkioside D (5), aspidistrin (6), tigogenin-3-O-β-D-lucotrioside (7), desglucolanatigonin II (8), and degalactotigonin (9), were isolated from Solanum lyratum Thunb. Their cytotoxic activities were tested in two cancer cell lines by MTT method. One of the steroidal glycosides (6) showed significant cytotoxic activity against gastric cancer SGC7901 and liver cancer BEL-7402 cells.
Alkaloids ; chemistry ; isolation & purification ; toxicity ; Antineoplastic Agents ; chemistry ; isolation & purification ; toxicity ; Cell Line, Tumor ; Cell Survival ; drug effects ; Glycosides ; chemistry ; pharmacology ; toxicity ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Phytosterols ; chemistry ; isolation & purification ; toxicity ; Plant Extracts ; chemistry ; toxicity ; Plants, Medicinal ; chemistry ; Solanum ; chemistry ; Sterols ; chemistry ; pharmacology ; toxicity

Objective Based on the different physiological characteristics of the mastoid skin and soft tissue in congenital microtia malformation ,the different ear reconstructivemethod were respectively applied for the individuals with microtia .And the feasibility of personalized treatment to microtia patients was explored in this study .Method Considering different thickness and tightness in mastoid hairless skin and soft tissue,2129 microtia patients were received the skin expansionmethod of ear reconstruction surgery , while 1321 cases were treated with Nagata ' s technique, and 330 cases with skin and fascia expansionmethod . Result With average 10-month follow-up,1944 ( 91.31％) cases using the mastoid skin expansionmethod were satisfied with the outcome of the reconstructed ear including three dimensional position and subunit appearance.305(92.42％)cases using the skin and fascia expansionmethod were satisfied with theresult .1264 (95.69％) cases using Nagata ' s two—stagemethod received satisfactory outcomes .49 ( 3.71％) cases showed partial exposure of the cartilage framework .There were no postoperative complications , such as chest wall deformity or affected normal physical function .Conclusion Based on the different physiological characteristics of the mastoid skin and soft tissue ,it's beneficial to select individualized operationalmethod in ear reconstruction for congenital microtia among Chinese patients .

Objective Based on the different physiological characteristics of the mastoid skin and soft tissue in congenital microtia malformation ,the different ear reconstructivemethod were respectively applied for the individuals with microtia .And the feasibility of personalized treatment to microtia patients was explored in this study .Method Considering different thickness and tightness in mastoid hairless skin and soft tissue,2129 microtia patients were received the skin expansionmethod of ear reconstruction surgery , while 1321 cases were treated with Nagata ' s technique, and 330 cases with skin and fascia expansionmethod . Result With average 10-month follow-up,1944 ( 91.31％) cases using the mastoid skin expansionmethod were satisfied with the outcome of the reconstructed ear including three dimensional position and subunit appearance.305(92.42％)cases using the skin and fascia expansionmethod were satisfied with theresult .1264 (95.69％) cases using Nagata ' s two—stagemethod received satisfactory outcomes .49 ( 3.71％) cases showed partial exposure of the cartilage framework .There were no postoperative complications , such as chest wall deformity or affected normal physical function .Conclusion Based on the different physiological characteristics of the mastoid skin and soft tissue ,it's beneficial to select individualized operationalmethod in ear reconstruction for congenital microtia among Chinese patients .

Objective To evaluate the efficacy and safety of Houpu Paiqi mixture in treatment of functional dyspepsia (FD)with abdominal distension symptom.Methods From July 2014 to June 2015 , in nine centers,a total of 162 FD patients with abdominal distension symptom and met Rome Ⅲpostprandial distress syndrome (PDS)diagnostic criteria were enrolled.All patients were randomly divided into trial group and control group,81 patients in either group.The patients of trial group and control group took Houpu Paiqi mixture or placebo,respectively,25 mL per time,twice daily,and both the courses of treatment were two weeks.Before and after the treatment,the improvement of main symptoms,total clinical efficacy rate and efficacy of traditional medicine between two groups were compared.Chi square test,Fisher exact probability method and Wilcoxon test were performed for statistical analysis.Results According to the results of per-protocol (PP)analysis,the total efficacy rate of trial group and control group was 69.4% (50/72)and 59.2% (42/71),respectively,and there was no statistically significant difference in total efficacy rate between the two groups (χ2 =1 .650,P =0.199 ). And there was no statistically significant difference in the improvement of PDS main symptoms(postprandial fullnessand early satiety)between the two groups (56.3% ±27.9% vs 54.4% ±32.1%,t =0.606,P =0.727 ).For those with baseline symptom score over 14,median early satiety score of trial group after the treatment was 0,which was lower than that of control group,and the difference was statistically significant (Z =-2.370,P =0.018).The total efficacy rate of traditional medicine of trial group was 80.8% (59/73 )and that of control group was 72.0% (54/75 ),and the difference was not statistically significant (χ2 = 0.676,P =0.411 ).Conclusion Houpu Paiqi mixture has certain efficacy in FD with abdominal distension,and could be used for the treatment of PDS-predominant FD.

OBJECTIVETo investigate the emergency treatment for large amputated ear defect.

METHODSFrom Feb. 2010 to Oct. 2013, 5 cases with large unilateral amputated ear defects were treated. The amputated auricular cartilage was replanted subcutaneously in mastoid area at the first stage. Cranioauricular sulcus was reconstructed and skin grafting was performed at the second stage.

RESULTSAll cases were followed up for 3-6 months with satisfactory result. The reconstructed helix, scapha and cavity of auricular concha had similar color and elasticity as the ear at healthy side. Scar at donor sites, such as inguinal region and armpit, was inconspicuous.

CONCLUSIONSThe method of auricular cartilage replantation is an effective way for emergency treatment of large amputated auricular defect with less morbidity at donor site.

Adolescent ; Adult ; Ear Cartilage ; transplantation ; Ear, External ; injuries ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Replantation ; Treatment Outcome ; Young Adult

AIM: To study the chemical constituents of stems of Gymnema sylvestre (Retz.) Schult. METHODS: Chromatographic techniques using silica gel, C18 reversed phase silica gel, and prep-HPLC were used. The structures were elucidated on the basis of MS and spectroscopic analysis (1D and 2D NMR), as well as chemical methods. RESULTS: Seven compounds were isolated and their structures were elucidated as conduritol A (1), stigmasterol (2), lupeol (3), stigmasterol-3-O-β-D-glucoside (4), the sodium salt of 22α-hydroxy-longispinogenin-3-O-β-D-glucopyranosyl-(1→3)-β-D-glu-curono-pyranosyl-28-O-α-L-rhamnopyranoside (5), oleanolic acid-3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (6), and the sodium salt of 22α-hydroxy-longispinogenin 3-O-β-D-glucuronopyranosyl-28-O-α-L-rhamnopyranoside (7). The inhibition activities of compounds 1, 5-7 on non-enzymatic glycation of protein in vitro were evaluated. CONCLUSION Compound 7 is a new triterpenoid saponin. It was shown that compounds 1, 5-7 have weak inhibition activities for non-enzymatic glycation of protein in vitro.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Gymnema sylvestre ; chemistry ; Molecular Structure ; Plant Stems ; chemistry

Objective To explore the efficacy and safety of endoscopic balloon dilatation of small bowel stricture in Crohn′s disease with single balloon enteroscopy (SBE).Methods Seven Crohn′s disease patients (four males and three females with a mean age of 37 years) were underwent 10 times dilatation.Before performance,Crohn′s disease with varying degrees of intestinal obstruction was confirmed by image and pathological examinations.There were 8 severe strictures,6 strictures in jejunum.The dilatation was performed step by step with controlled radial expansiondilator (CRE) balloon.After dilatation,the scope could reach the further small bowel was taken as a standard.Results The overall suecess rate was 8 of 10.The average diameter of intestinal stricture was expanded from (4.1 ± 2.5) mm before therapy to (10.2 ±1.5) mm (P＜0.01),and the average distance of the further small bowel that the scope reached was 62 cm.Two patients underwent twice and three times of dilatation.After the performance,all patients′ symptoms of abdominal pain and obstruction relieved obviously and there were no severe complication of bleeding or perforation.After the performance,the average follow-up time was 14 months,two patients were treated by surgery and the other two underwent dilatation treatment again because of the recurrence of symptoms.The median symptom-free time was 15 months and 70％ of patients were without symptom recurrence in one year.Conclusion Endoscopic balloon dilatation of small bowel stricture with SBE is a new technology of endoscopic treatment,which is safe and effective in the treatment of Crohn's diseasecomplicated with intestinal obstruction.