Benchmarking spatial and single-cell transcriptomics integration methods for transcript distribution prediction and cell type deconvolution.

Spatial transcriptomics approaches have substantially advanced our capacity to detect the spatial distribution of RNA transcripts in tissues, yet it remains challenging to characterize whole-transcriptome-level data for single cells in space. Addressing this need, researchers have developed integration methods to combine spatial transcriptomic data with single-cell RNA-seq data to predict the spatial distribution of undetected transcripts and/or perform cell type deconvolution of spots in histological sections. However, to date, no independent studies have comparatively analyzed these integration methods to benchmark their performance. Here we present benchmarking of 16 integration methods using 45 paired datasets (comprising both spatial transcriptomics and scRNA-seq data) and 32 simulated datasets. We found that Tangram, gimVI, and SpaGE outperformed other integration methods for predicting the spatial distribution of RNA transcripts, whereas Cell2location, SpatialDWLS, and RCTD are the top-performing methods for the cell type deconvolution of spots. We provide a benchmark pipeline to help researchers select optimal integration methods to process their datasets.

Visible-Light-Induced Monofluoroalkenylation and gem-Difluoroallylation of Inactivated C(sp3)-H Bonds via 1,5-Hydrogen Atom Transfer (HAT).

The direct monofluoroalkenylation of C(sp3)-H bonds is of great importance and quite challenging. Current methods have been restricted to the monofluoroalkenylation of activated C(sp3)-H bonds. Here, we reported the photocatalyzed C(sp3)-H monofluoroalkenylation of inactivated C(sp3)-H bonds with gem-difluoroalkenes via 1,5-hydrogen atom transfer. This process shows good functional group tolerance, such as halides (F, Cl), nitrile, sulfone, ester, and pyridine, and good γ-selectivity. Moreover, this method succeeds in the photocatalyzed gem-difluoroallylation of inactivated C(sp3)-H with α-trifluoromethyl alkenes.

A novel method for extracting circulating cell-free DNA from whole blood samples and its utility in the non-invasive prenatal test.

OBJECTIVE: We verified a magnetic bead-based, simple, and fast method for circulating cell-free DNA (cfDNA) extraction from whole blood samples(CEWB) and characterised its utility in non-invasive prenatal testing (NIPT). METHOD: We extracted cfDNA from both plasma and whole blood of the patients using CEWB and compared it to that extracted using a Qiagen extraction kit; droplet digital polymerase chain reaction test was used to calculate the fragment size bias. In all, 304 samples were used for NIPT. RESULTS: The CEWB group (mean ± standard deviation [SD]: 4.34 ± 0.41 ng/ml plasma) reported less DNA weight yield than the Qiagen group (4.90 ± 0.50 ng/ml plasma). There was no significant difference between the CEWB group and the Qiagen group in the gene fragments (136 bp: p = 0.064 and 420 bp: p = 0.534). In a parallel cohort study to characterise the utility of the CEWB method in NIPT, the treatment group extracted by CEWB showed a sensitivity of 100%, a specificity of 99.65%, and a positive predictive value of 95%. CONCLUSIONS: This study demonstrated that CEWB achieves an acceptable yield of DNA without contamination from genomic DNA. Subsequent clinical experiments in a parallel cohort indicated its utility for NIPT.

Melatonin inhibiting the survival of human gastric cancer cells under ER stress involving autophagy and Ras-Raf-MAPK signalling.

Melatonin exhibits antitumour activities in the treatment of many human cancers. In the present study, we aimed to improve the therapeutic potential of melatonin in gastric cancer. Our results confirmed that melatonin dose-dependently suppressed the proliferation and necrosis, and increased G0/G1 phase arrest, apoptosis, autophagy and endoplasmic reticulum (ER) stress. The Ras-Raf-MAPK signalling pathway was activated in cells after melatonin treatment. RNA-seq was performed and GSEA analysis further confirmed that many down-regulated genes in melatonin-treated cells were associated with proliferation. However, GSEA analysis also indicated that many pathways related to metastasis were increased after melatonin treatment. Subsequently, combinatorial treatment was conducted to further investigate the therapeutic outcomes of melatonin. A combination of melatonin and thapsigargin increased the apoptotic rate and G0/G1 cell cycle arrest when compared to treatment with melatonin alone. Melatonin in combination with thapsigargin triggered the increased expression of Bip, LC3-II, phospho-Erk1/2 and phospho-p38 MAPK. In addition, STF-083010, an IRE1a inhibitor, further exacerbated the decrease in survival rate induced by combinatorial treatment with melatonin and thapsigargin. Collectively, melatonin was effective in gastric cancer treatment by modifying ER stress.

Potential of fecal microbiota for detection and postoperative surveillance of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers. In recent studies, the gut microbiota has been reported to be potentially involved in aggravating or favoring CRC development. However, little is known about the microbiota composition in CRC patients after treatment. In this study, we explored the fecal microbiota composition to obtain a periscopic view of gut microbial communities. We analyzed microbial 16S rRNA genes from 107 fecal samples of Chinese individuals from three groups, including 33 normal controls (NC), 38 CRC patients (Fa), and 36 CRC post-surgery patients (Fb). RESULTS: Species richness and diversity were decreased in the Fa and Fb groups compared with that of the NC group. Partial least squares discrimination analysis showed clustering of samples according to disease with an obvious separation between the Fa and NC, and Fb and NC groups, as well as a partial separation between the Fa and Fb groups. Based on linear discriminant analysis effect size analysis and a receiver operating characteristic model, Fusobacterium was suggested as a potential biomarker for CRC screening. Additionally, we found that surgery greatly reduced the bacterial diversity of microbiota in CRC patients. Some commensal beneficial bacteria of the intestinal canal, such as Faecalibacterium and Prevotella, were decreased, whereas the drug-resistant Enterococcus was visibly increased in CRC post-surgery group. Meanwhile, we observed a declining tendency of Fusobacterium in the majority of follow-up CRC patients who were still alive approximately 3 y after surgery. We also observed that beneficial bacteria dramatically decreased in CRC patients that recidivated or died after surgery. This revealed that important bacteria might be associated with prognosis. CONCLUSIONS: The fecal bacterial diversity was diminished in CRC patients compared with that in NC. Enrichment and depletion of several bacterial strains associated with carcinomas and inflammation were detected in CRC samples. Fusobacterium might be a potential biomarker for early screening of CRC in Chinese or Asian populations. In summary, this study indicated that fecal microbiome-based approaches could be a feasible method for detecting CRC and monitoring prognosis post-surgery.

Mutation characteristics of cancer susceptibility genes in Chinese ovarian cancer patients.

Introduction: The association between mutations in susceptibility genes and the occurrence of ovarian cancer has been extensively studied. Previous research has primarily concentrated on genes involved in the homologous recombination repair pathway, particularly BRCA1 and BRCA2. However, a wider range of genes related to the DNA damage response pathways has not been fully explored. Methods: To investigate the mutation characteristics of cancer susceptibility genes in the Chinese ovarian cancer population and the associations between gene mutations and clinical data, this study initially gathered a total of 1171 Chinese ovarian cancer samples and compiled a dataset of germline mutations in 171 genes. Results: In this study, it was determined that MC1R and PRKDC were high-frequency ovarian cancer susceptibility genes in the Chinese population, exhibiting notable distinctions from those in European and American populations; moreover high-frequency mutation genes, such as MC1R: c.359T>C and PRKDC: c.10681T>A, typically had high-frequency mutation sites. Furthermore, we identified c.8187G>T as a characteristic mutation of BRCA2 in the Chinese population, and the CHEK2 mutation was significantly associated with the early onset of ovarian cancer, while the CDH1 and FAM175A mutations were more prevalent in Northeast China. Additionally, Fanconi anemia pathway-related genes were significantly associated with ovarian carcinogenesis. Conclusion: In summary, this research provided fundamental data support for the optimization of ovarian cancer gene screening policies and the determination of treatment, and contributed to the precise intervention and management of patients.

SPACEL: deep learning-based characterization of spatial transcriptome architectures.

Spatial transcriptomics (ST) technologies detect mRNA expression in single cells/spots while preserving their two-dimensional (2D) spatial coordinates, allowing researchers to study the spatial distribution of the transcriptome in tissues; however, joint analysis of multiple ST slices and aligning them to construct a three-dimensional (3D) stack of the tissue still remain a challenge. Here, we introduce spatial architecture characterization by deep learning (SPACEL) for ST data analysis. SPACEL comprises three modules: Spoint embeds a multiple-layer perceptron with a probabilistic model to deconvolute cell type composition for each spot in a single ST slice; Splane employs a graph convolutional network approach and an adversarial learning algorithm to identify spatial domains that are transcriptomically and spatially coherent across multiple ST slices; and Scube automatically transforms the spatial coordinate systems of consecutive slices and stacks them together to construct a 3D architecture of the tissue. Comparisons against 19 state-of-the-art methods using both simulated and real ST datasets from various tissues and ST technologies demonstrate that SPACEL outperforms the others for cell type deconvolution, for spatial domain identification, and for 3D alignment, thus showcasing SPACEL as a valuable integrated toolkit for ST data processing and analysis.

Recent advances in difunctionalization of alkenes using pyridinium salts as radical precursors.

In this review, we summarise the recent applications of pyridinium salts in the radical-mediated difunctionalization of alkenes. Pyridinium salts are a privileged class of compounds that show great utility in natural products and synthetic chemistry. Various organic transformations of pyridinium salts, especially in radical chemistry, have been developed in recent years. We prepared this review based on the two distinguished properties of pyridinium salts in radical transformation: (1) pyridinium salts can easily undergo single electron reduction to deliver X radicals. (2) Pyridinium salts are highly electrophilic so that alkyl radical intermediates can easily add to the pyridine core. Based on the role of pyridinium salts in difunctionalization of alkenes, the main body of this review is divided into three parts: (1) using pyridinium salts as X transfer reagents. (2) Using pyridinium salts as novel pyridine transfer reagents. (3) Using pyridinium salts as bifunctional reagents (X and pyridine). The C2 and C4 selectivity during pyridylation is discussed in detail. We hope that this review will provide a comprehensive overview of this topic and promote the wider development and application of pyridinium salts.

Effects of Waterlogging on Soybean Rhizosphere Bacterial Community Using V4, LoopSeq, and PacBio 16S rRNA Sequence.

Waterlogging causes a significant reduction in soil oxygen levels, which in turn negatively affects soil nutrient use efficiency and crop yields. Rhizosphere microbes can help plants to better use nutrients and thus better adapt to this stress, while it is not clear how the plant-associated microbes respond to waterlogging stress. There are also few reports on whether this response is influenced by different sequencing methods and by different soils. In this study, using partial 16S rRNA sequencing targeting the V4 region and two full-length 16S rRNA sequencing approaches targeting the V1 to V9 regions, the effects of waterlogging on soybean rhizosphere bacterial structure in two types of soil were examined. Our results showed that, compared with the partial 16S sequencing, full-length sequencing, both LoopSeq and Pacific Bioscience (PacBio) 16S sequencing, had a higher resolution. On both types of soil, all the sequencing methods showed that waterlogging significantly affected the bacterial community structure of the soybean rhizosphere and increased the relative abundance of Geobacter. Furthermore, modular analysis of the cooccurrence network showed that waterlogging increased the relative abundance of some microorganisms related to nitrogen cycling when using V4 sequencing and increased the microorganisms related to phosphorus cycling when using LoopSeq and PacBio 16S sequencing methods. Core microorganism analysis further revealed that the enriched members of different species might play a central role in maintaining the stability of bacterial community structure and ecological functions. Together, our study explored the role of microorganisms enriched at the rhizosphere under waterlogging in assisting soybeans to resist stress. Furthermore, compared to partial and PacBio 16S sequencing, LoopSeq offers improved accuracy and reduced sequencing prices, respectively, and enables accurate species-level and strain identification from complex environmental microbiome samples. IMPORTANCE Soybeans are important oil-bearing crops, and waterlogging has caused substantial decreases in soybean production all over the world. The microbes associated with the host have shown the ability to promote plant growth, nutrient absorption, and abiotic resistance. High-throughput sequencing of partial 16S rRNA is the most commonly used method to analyze the microbial community. However, partial sequencing cannot provide correct classification information below the genus level, which greatly limits our research on microbial ecology. In this study, the effects of waterlogging on soybean rhizosphere microbial structure in two soil types were explored using partial 16S rRNA and full-length 16S gene sequencing by LoopSeq and Pacific Bioscience (PacBio). The results showed that full-length sequencing had higher classification resolution than partial sequencing. Three sequencing methods all indicated that rhizosphere bacterial community structure was significantly impacted by waterlogging, and the relative abundance of Geobacter was increased in the rhizosphere in both soil types after suffering waterlogging. Moreover, the core microorganisms obtained by different sequencing methods all contain species related to nitrogen cycling. Together, our study not only explored the role of microorganisms enriched at the rhizosphere level under waterlogging in assisting soybean to resist stress but also showed that LoopSeq sequencing is a less expensive and more convenient method for full-length sequencing by comparing different sequencing methods.

A transcriptome atlas and interactive analysis platform for autoimmune disease.

With the rapid development of next-generation sequencing technology, many laboratories have produced a large amount of single-cell transcriptome data of blood and tissue samples from patients with autoimmune diseases, which enables in-depth studies of the relationship between gene transcription and autoimmune diseases. However, there is still a lack of a database that integrates the large amount of autoimmune disease transcriptome sequencing data and conducts effective analysis. In this study, we developed a user-friendly web database tool, Interactive Analysis and Atlas for Autoimmune disease (IAAA), which integrates bulk RNA-seq data of 929 samples of 10 autoimmune diseases and single-cell RNA-seq data of 783 203 cells in 96 samples of 6 autoimmune diseases. IAAA also provides customizable analysis modules, including gene expression, difference, correlation, similar gene detection and cell-cell interaction, and can display results in three formats (plot, table and pdf) through custom parameters. IAAA provides valuable data resources for researchers studying autoimmune diseases and helps users deeply explore the potential value of the current transcriptome data. IAAA is available. Database URL: http://galaxy.ustc.edu.cn/IAAA.

Application research of chronic disease health management in an urban community based on the PRECEDE-PROCEED model in the long-term management of diabetes mellitus.

OBJECTIVE: To evaluate the application of chronic disease health management in an urban community in the long-term management of diabetes mellitus (DM) based on the PRECEDE-PROCEED model. METHODS: The PRECEDE-PROCEED model combines PRECEDE (predisposing, enabling and reinforcing constructs in educational diagnosis and evaluation) with PROCEED (policy, management and organization constructs in educational and environmental intervention). A total of 96 diabetic patients treated in our hospital were selected and divided into two groups by random number table, with 48 cases in each group. The routine group was given routine health management, while the PP group was given the urban community chronic disease health management based on the PRECEDE-PROCEED model in addition to the routine health management. After six months of management, the patients' effect was evaluated by comparing the blood glucose, diabetes knowledge, self-efficacy, self-management level and quality of life between the two groups. RESULTS: The FPG, 2hPG and HbAlc levels of the PP group were lower than those of the routine group after six months of management (all P<0.05). The 6-month awareness rate, self-efficacy, self-management level and quality of life scores of the PP group were higher than those of the routine group (all P<0.05). CONCLUSION: The chronic disease health management in urban communities based on the PRECEDE-PROCEED model in long-term diabetes management can effectively improve patients' diabetes knowledge, lower blood glucose levels, improve self-efficacy and self-management, and improve the quality of life.

Proteomics study of colorectal cancer and adenomatous polyps identifies TFR1, SAHH, and HV307 as potential biomarkers for screening.

Colorectal cancer (CRC) is a malignant tumour with high morbidity and mortality worldwide. Efficient screening strategies for CRC and pre-cancerous lesions can promote early medical intervention and treatment, thereby reducing morbidity and mortality. Proteins are generally considered key biomarkers of cancer. Herein, we performed a quantitative, original-tissue proteomics study in a cohort of ninety patients from pre-cancerous to cancerous conditions via liquid chromatography-tandem mass spectrometry. In total, 134,812 peptides, 8697 proteins, 2355 union differentially expressed proteins (DEPs), and 409 shared DEPs (compared with adjacent tissues) were identified. The number of DEPs indicated a positive correlation with increasing severity of illness. The union and shared DEPs were both enriched in the KEGG pathway of focal adhesion, metabolism of xenobiotics by cytochrome P450, and drug metabolism by cytochrome P450. Among the 2355 union DEPs, 32 were selected for identification and validation by multiple reaction monitoring from twenty plasma specimens. Of these, three proteins, transferrin receptor protein 1 (TFR1), adenosylhomocysteinase (SAHH), and immunoglobulin heavy variable 3-7 (HV307), were significantly differentially expressed and displayed the same expression pattern in plasma as observed in the tissue data. In conclusion, TFR1, SAHH, and HV307 may be considered as potential biomarkers for CRC screening. SIGNIFICANCE: Although CRC is a malignant tumour with high morbidity and mortality worldwide, efficient screening strategies for CRC and pre-cancerous lesions can play an important role in addressing these issues. Screening of molecular biomarkers provide a non-invasive, cost-effective, and efficient approach. Proteins are generally considered key molecular biomarkers of cancer. Our study reports a quantitative proteomics analysis of protein biomarkers for colorectal cancer (CRC) and adenomatous polyps, and identifies TFR1, SAHH, and HV307 as potential biomarkers for screening. This research makes a significant contribution to the literature as although mass spectrometry-based proteomics research has been widely used for clinical research, its application to clinical translation as parallel specimens ranging from pre-cancerous to cancerous tissues-according to the degree of disease progression-has not been readily assessed.

Comparative Analysis of Sample Extraction and Library Construction for Shotgun Metagenomics.

Human fecal specimens, serve as important materials, are widely used in the field of microbiome research, in which inconsistent results have been a pressing issue. The possible attribute factors have been proposed including the specimen status after preservation, extracted DNA quality, library preparation protocol, and sample DNA input. In this study, quality comparisons for shotgun metagenomics sequencing were performed between 2 DNA extraction methods for fresh and freeze-thaw samples, 2 library preparation protocols, and various sample inputs. The results indicate that Mag-Bind® Universal Metagenomics Kit (OM) outperformed DNeasy PowerSoil Kit (QP) with a higher DNA quantity. Controlling on library preparation protocol, OM detected on-average more genes than QP. For library construction comparison by controlling on the same DNA sample, KAPA Hyper Prep Kit (KH) outperformed the TruePrep DNA Library Prep Kit V2 (TP) with the higher number of detected genes number and Shannon index. No significant differences were found in taxonomy between 2 library preparation protocols using the fresh, freeze-thaw and mock community samples. No significant difference was observed between 250 and 50 ng DNA inputs for library preparation on both fresh and freeze-thaw samples. Through the preliminary study, a combined protocol is recommended for performing metagenomics studies, by using OM method plus KH protocol as well as suitable DNA quantity on either fresh or freeze-thaw samples. Our findings provide clues for potential variations from various DNA extraction methods, library protocols, and sample DNA inputs, which are critical for consistent and comprehensive profiling of the human gut microbiome.

Sodium borohydride-assisted synthesis of strontium substituted lanthanum cobaltate with in-situ generated cobaltosic oxide: Towards enhanced oxygen evolution reaction in alkaline media.

Based on the intrinsic behaviour of doped Co-based perovskite to generate the second phase of Co3O4, a novel strategy was developed to synthesize a hybrid catalyst consisting of La1-xSrxCoO3-δ (x = 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0) and in-situ generated Co3O4 in the presence of NaBH4. When x increased to 1.0, a well-designed integration (SrCoO2.5@Co3O4) was obtained which displayed the optimal OER activity with an overpotential of 330 mV at 10 mA cm-2, a small Tafel slope of 66.7 mV dec-1 and terrific durability in alkaline media. This excellent performance can be attributed to the auxiliary of the in-situ generated Co3O4 for SrCoO2.5 which modifies the chemical states of Co cations, compensates for the unsatisfactory electrical conductivity of SrCoO2.5 while preserves oxygen vacancies, boosts the content of lattice oxygen and exposes more active sites. This work is expected to provide a new mind to design effective electrocatalysts towards water splitting.

Capsule oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis: a randomized, double blind, placebo-controlled, multicenter clinical study.

AIM: To evaluate the efficacy and safety of oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: It was a randomized, double blind, placebo-controlled, multicenter clinical study. One hundred and forty-four patients were divided into oxymatrine capsule group(group A) and placebo group (group B). The course was 52 wk. Patients were visited once every 12 wk and the last visit was at 12 wk after cessation of the treatment. All patients had liver biopsy before treatment. part of them had a second biopsy at the end of therapy. Clinical symptoms, liver function test, serum markers of hepatic fibrosis were tested. Ultrasound evaluation was performed before, during and at the end of therapy. RESULTS: One hundred and forty-four patients enrolled in the study. Of them 132 patients completed the study according to the protocol,49 patients had liver biopsy twice (25 patients in group A and 24 in group B). At the end of therapy, significant improvements in hepatic fibrosis and inflammatory activity based on Semi-quantitative scoring system (SSS) were achieved in group A. The total effective rate of the treatment was 48.00%, much higher than that of 4.17% in group B (P<0.05). Significant improvement in serum markers of hepatic fibrosis such as hyaluronic acid (HA) and type III procollagenic peptide (P III P) in group A was seen (P<0.05). The total effective rate of serum markers at the end of therapy in group A was 68.19%, much higher than that of 34.85% in group B (P<0.05). The total effective rate of noninvasive markers at the end of therapy in group A was 66.67%, much higher than that of 30.30% in group B (P<0.05). The rate of adverse events was similar in two groups. CONCLUSION: Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis.

Oxymatrine therapy for chronic hepatitis B: a randomized double-blind and placebo-controlled multi-center trial.

AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B. METHODS: A randomised double-blind and placebo-controlled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo. After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed. RESULTS: Among the 216 patients, six were dropped off, and 11 inconsistent with the standard were excluded. Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47% became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33% became normal in ALT level, 43.33% and 39.29% became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00% became normal in ALT level, 7.46% and 6.45% became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84% in the capsule treated patients, and 33.33% and 50.00% in the injection treated patients, and 2.99% and 41.79% in the placebo treated patients, respectively. There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule, injection and placebo were 7.77%, 6.67% and 8.82%, respectively. There was no statistically significant difference among them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

[Oxymatrine in the treatment of chronic hepatitis B for one year: a multicenter random double-blind placebo-controlled trial].

OBJECTIVE: To evaluate the efficacy and safety of oxymatrine in the treatment of chronic hepatitis B. METHODS: A multicenter randomized double-blind placebo-controlled trial was conducted. A total of 144 patients with chronic hepatitis B entered the study for 52 weeks; of them 72 received oxymatrine, and 72 received a placebo. Before and after the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reactions were observed. RESULTS: In 144 patients, 14 were dropped and excluded due to inconsistencies in the included standard. Therefore, the efficacy and safety of 130 patients were analyzed. After being treated for 52 weeks, 70.77% of the patients in the study group had a normal ALT level, and in 43.08% and 33.33% their HBV DNA and HBeAg became negative. In the placebo group, 39.68% had normal ALT level, and 12.31% and 3.33% had their HBV DNA and HBeAg become negative. The rates of complete response and partial response in the oxymatrine group were 23.08% and 58.46%, and in the placebo group they were 3.08% and 44.62%. They were significantly higher in the oxymatrine group than in the placebo group. In the oxymatrine treated patients, 12 weeks after its withdrawal, 60.00% had a normal ALT level, 41.54% and 23.33% had both HBV DNA and HBeAg negative. In the placebo group, 31.75% had a normal ALT level, 3.08% and 1.67% had both HBV DNA and HBeAg negative. The rates of complete response and partial response in the oxymatrine group were 21.54% and 47.69%, and in the placebo group they were 0 and 41.54%. They were significantly higher in the study group than in the placebo group. The adverse reaction rates of oxymatrine in the study and the placebo group were 7.69% and 6.15%, respectively, but there was no statistical significant difference between them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants.

Targeted capture combined with massively parallel exome sequencing is a promising approach to identify genetic variants implicated in human traits. We report exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold. On average, about 95% of the target regions were covered by at least one read. We identified 121,870 SNPs in the sample population, including 53,081 coding SNPs (cSNPs). Using a statistical method for SNP calling and an estimation of allelic frequencies based on our population data, we derived the allele frequency spectrum of cSNPs with a minor allele frequency greater than 0.02. We identified a 1.8-fold excess of deleterious, non-syonomyous cSNPs over synonymous cSNPs in the low-frequency range (minor allele frequencies between 2% and 5%). This excess was more pronounced for X-linked SNPs, suggesting that deleterious substitutions are primarily recessive.

Sequencing of 50 human exomes reveals adaptation to high altitude.

Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP's association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude.

The phylogeny and expression pattern of APETALA2-like genes in rice.

The multigene families undergo birth-and-death evolution and thus contribute to biological innovations. The APETALA2-like genes belong to the euAP2 group of the AP2 gene family. These genes are characterized by several distinct motifs and exist in ferns, gymnosperms, and angiosperms. The phylogenetic analysis indicated that these genes have undergone the birth-and-death evolution. The five APETALA2-like genes in rice (Oryza sativa L.) display redundant but distinct expression patterns as demonstrated by RT-PCR and in situ hybridization. The potential functions of these genes were discussed on the basis of phylogenetic and expression pattern.