Xiaoyao Pills, a Chinese patent medicine, treats mild and moderate depression: A randomized clinical trial combined with DNA methylation analysis.

BACKGROUND: Xiaoyao pills (XYP) is a commercial Chinese patent medicine used in the treatment of depression. However, the mechanisms underlying its therapeutic effects, as well as the patients who can benefit from XYP, have not been evaluated so far. OBJECTIVES: To this end, we conducted a double-blinded, random, and placebo-controlled clinical trial of orally administered XYP in patients with depression. METHODS: The 17-item Hamilton Depression Rating Scale (HAMD-17) scores were recorded at baseline, and every 2 weeks after the start of treatment. To further elucidate the epigenetic mechanism of XYP, we performed mRNA sequencing and genome-wide DNA methylation sequencing using peripheral blood leukocytes of patients and healthy. RESULTS: XYP effectively alleviated the symptoms in patients with mild or moderate depressive disorders, particularly that of psychomotor retardation. XYP restored aberrant gene expression and DNA methylation patterns associated with depression, and the normalization of DNA methylation correlated with downregulation of several genes. In addition, altered DNA methylation levels in the XYP-treated samples were attributed to increased expression of the DNA methyltransferase DNMT1. CONCLUSIONS: Our study provides new insights into the epigenetic mechanism underlying depression and the therapeutic effects of XYP, along with an experimental basis for using XYP in the treatment of depression. TRIAL REGISTRATION INFORMATION: The name of the registry and number: U.S. CLINICAL TRIALS REGISTRY: The link to the registration: ClinicalTrials.gov ISRCTN12746343 (https://www.isrctn.com/ISRCTN12746343). The name of the trial register is "Efficacy and safety of the Xiaoyao pill for improving the clinical symptoms of stagnation of liver qi (chi) and spleen deficiency". The clinical trial registration number is ISRCTN12746343.

Evaluation of compliance of CONSORT-CHM formula 2017 in randomized controlled trials of Chinese herbal medicine formulas: protocol of a five-year review.

Background: The CONSORT Extension for Chinese Herbal Medicine Formula 2017 (CONSORT-CHM Formula 2017) has established a reporting standard for randomized controlled trials (RCTs) of Chinese Herbal Medicine Formula (CHMF) interventions; however, its adherence and implications for the design and execution of study design remain ambiguous. It is necessary to evaluate the level of compliance with the CONSORT-CHM Formula 2017 in RCTs conducted over the past 5 years, and to determine the reporting quality of clinical trials in this field. Methods: First, a systematic search is conducted for RCTs on CHMF in EBM Reviews, Allied and Complementary Medicine (AMED), Embase, Ovid-MEDLINE(R), Wanfang data, China National Knowledge Infrastructure (CNKI), VIP Chinese Medical Journal Database (VIP) and Chinese Biomedical Literature (CBM) database, that encompassed CHMF interventional RCTs published from 1 January 2018 to 8 June 2022, with language restriction to English or Chinese. Second, a descriptive analysis will be performed regarding the study design and general characteristics of the included trials. Third, for the quality assessment, we have subdivided the CONSORT-CHM Formula 2017 checklist (consisting of 22 extended items) into a total of 42 sub-questions to facilitate scoring, with a specific focus on the description, quality control, and safety assessment of CHMF interventions. Professional training and a pilot test on 100 randomly selected articles will be provided for all reviewers. Throughout this process, a standard operating procedure (SOP) for quality assessment will be developed to ensure consistency. Each item will be assessed by two reviewers in a paired back-to-back manner, and the compliance rate will be calculated to assess inter-rater agreement. Discussion: This review will identify the current reporting characteristics and quality of CHMF interventional studies and further evaluate the impact of CONSORT-CHM Formula 2017. The results may provide suggestions for future application or promotion of the guideline. Registration: The study has been registered on Open Science Framework (https://osf.io/xpn7f).

Stereospecific synthesis of silicon-stereogenic optically active silylboranes and general synthesis of chiral silyl Anions.

Silicon-stereogenic optically active silylboranes could potentially allow the formation of chiral silyl nucleophiles as well as the synthesis of various chiral silicon compounds. However, the synthesis of such silicon-stereogenic silylboranes has not been achieved so far. Here, we report the synthesis of silicon-stereogenic optically active silylboranes via a stereospecific Pt(PPh3)4-catalyzed Si-H borylation of chiral hydrosilanes, which are synthesized by stoichiometric and catalytic asymmetric synthesis, in high yield and very high or perfect enantiospecificity (99% es in one case, and >99% es in the others) with retention of the configuration. Furthermore, we report a practical approach to generate silicon-stereogenic silyl nucleophiles with high enantiopurity and configurational stability using MeLi activation. This protocol is suitable for the stereospecific and general synthesis of silicon-stereogenic trialkyl-, dialkylbenzyl-, dialkylaryl-, diarylalkyl-, and alkylary benzyloxy-substituted silylboranes and their corresponding silyl nucleophiles with excellent enantiospecificity (>99% es except one case of 99% es). Transition-metal-catalyzed C-Si bond-forming cross-coupling reactions and conjugate-addition reactions are also demonstrated. The mechanisms underlying the stability and reactivity of such chiral silyl anion were investigated by combining NMR spectroscopy and DFT calculations.

A Chinese indicine pangenome reveals a wealth of novel structural variants introgressed from other Bos species.

Chinese indicine cattle harbor a much higher genetic diversity compared with other domestic cattle, but their genome architecture remains uninvestigated. Using PacBio HiFi sequencing data from 10 Chinese indicine cattle across southern China, we assembled 20 high-quality partially phased genomes and integrated them into a multiassembly graph containing 148.5 Mb (5.6%) of novel sequence. We identified 156,009 high-confidence nonredundant structural variants (SVs) and 206 SV hotspots spanning ∼195 Mb of gene-rich sequence. We detected 34,249 archaic introgressed fragments in Chinese indicine cattle covering 1.93 Gb (73.3%) of the genome. We inferred an average of 3.8%, 3.2%, 1.4%, and 0.5% of introgressed sequence originating, respectively, from banteng-like, kouprey-like, gayal-like, and gaur-like Bos species, as well as 0.6% of unknown origin. Introgression from multiple donors might have contributed to the genetic diversity of Chinese indicine cattle. Altogether, this study highlights the contribution of interspecies introgression to the genomic architecture of an important livestock population and shows how exotic genomic elements can contribute to the genetic variation available for selection.

A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes.

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5' untranslated region (5' UTR) of HOXB13 is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep.

A missense mutation in RRM1 contributes to animal tameness.

The increased tameness to reduce avoidance of human in wild animals has been long proposed as the key step of animal domestication. The tameness is a complex behavior trait and largely determined by genetic factors. However, the underlying genetic mutations remain vague and how they influence the animal behaviors is yet to be explored. Behavior tests of a wild-domestic hybrid goat population indicate the locus under strongest artificial selection during domestication may exert a huge effect on the flight distance. Within this locus, only one missense mutation RRM1I241V which was present in the early domestic goat ~6500 years ago. Genome editing of RRM1I241V in mice showed increased tameness and sociability and reduced anxiety. These behavioral changes induced by RRM1I241V were modulated by the alternation of activity of glutamatergic synapse and some other synapse-related pathways. This study established a link between RRM1I241V and tameness, demonstrating that the complex behavioral change can be achieved by mutations under strong selection during animal domestication.

Long divergent haplotypes introgressed from wild sheep are associated with distinct morphological and adaptive characteristics in domestic sheep.

The worldwide sheep population comprises more than 1000 breeds. Together, these exhibit a considerable morphological diversity, which has not been extensively investigated at the molecular level. Here, we analyze whole-genome sequencing individuals of 1,098 domestic sheep from 154 breeds, and 69 wild sheep from seven Ovis species. On average, we detected 6.8%, 1.0% and 0.2% introgressed sequence in domestic sheep originating from Iranian mouflon, urial and argali, respectively, with rare introgressions from other wild species. Interestingly, several introgressed haplotypes contributed to the morphological differentiations across sheep breeds, such as a RXFP2 haplotype from Iranian mouflon conferring the spiral horn trait, a MSRB3 haplotype from argali strongly associated with ear morphology, and a VPS13B haplotype probably originating from urial and mouflon possibly associated with facial traits. Our results reveal that introgression events from wild Ovis species contributed to the high rate of morphological differentiation in sheep breeds, but also to individual variation within breeds. We propose that long divergent haplotypes are a ubiquitous source of phenotypic variation that allows adaptation to a variable environment, and that these remain intact in the receiving population probably due to reduced recombination.

Design and characterization of a high-resolution multiple-SNP capture array by target sequencing for sheep.

The efficiency of molecular breeding largely depends on inexpensive genotyping arrays. In this study, we aimed to develop an ovine high-resolution multiple-single-nucleotide polymorphism (SNP) capture array, based on genotyping by target sequencing (GBTS) system with capture-in-solution (liquid chip) technology. All the markers were from 40K captured regions, including genes located within selective sweep regions, breed-specific regions, quantitative trait loci (QTL), and the potential functional SNPs on the sheep genome. The results showed that a total of 210K high-quality SNPs were identified in the 40K regions, indicating a high average capture ratio (99.7%) for the target genomic regions. Using genotyped data (n = 317) from liquid chip technology, we further performed genome-wide association studies (GWAS) to detect the genetic loci affecting sheep hair types and teat number. A single significant association signal for hair types was identified on 6.7-7.1 Mb of chromosome 25. The IRF2BP2 gene (chr25: 7,067,974-7,071,785), which is located within this genomic region, has been previously known to be involved in hair/wool traits in sheep. The results further showed a new candidate region around 26.4 Mb of chromosome 13, between the ARHGAP21 and KIAA1217 genes, that was significantly related to teat number in sheep. The haplotype patterns of this region also showed differences in animals with 2, 3, or 4 teats. Advances in using the high-accuracy and low-cost liquid chip are expected to accelerate sheep genomic and breeding studies in the coming years.

Large-scale genotyping platforms are valuable tools for animal selection and breeding programs. The bead chip has been widely used in both research and commercial applications for a long time. A highly efficient and economical genotyping platform has been developed recently. In the present study, by combining the advantages of resequencing and bead chips, we developed a high-resolution capture array based on target sequencing with capture-in-solution technology (liquid chip), including updated functional probes according to the latest research. We further evaluated this approach by using 317 individuals and found that 210K single-nucleotide polymorphisms can be accurately genotyped, confirming the ratio of the captured regions compared with the designed rations is around 99.7%. Genome-wide association studies conducted using this chip suggested IRF2BP2 gene may be involved in hair types and ARHGAP21-KIAA1217 locus may be related to teats number. The liquid chip with high accuracy and low cost can be widely used in genome-wide association studies and genome selection, supporting efforts in molecular breeding and genetic improvement of sheep.

Genomic analysis of indigenous goats in Southwest Asia reveals evidence of ancient adaptive introgression related to desert climate.

Understanding how evolutionary pressures related to climate change have shaped the current genetic background of domestic animals is a fundamental pursuit of biology. Here, we generated whole-genome sequencing data from native goat populations in Iraq and Pakistan. Combined with previously published data on modern, ancient (Late Neolithic to Medieval periods), and wild Capra species worldwide, we explored the genetic population structure, ancestry components, and signatures of natural positive selection in native goat populations in Southwest Asia (SWA). Results revealed that the genetic structure of SWA goats was deeply influenced by gene flow from the eastern Mediterranean during the Chalcolithic period, which may reflect adaptation to gradual warming and aridity in the region. Furthermore, comparative genomic analysis revealed adaptive introgression of the KITLG locus from the Nubian ibex ( C. nubiana) into African and SWA goats. The frequency of the selected allele at this locus was significantly higher among goat populations located near northeastern Africa. These results provide new insights into the genetic composition and history of goat populations in the SWA region.

Diagnostic value of radiomics in predicting Ki-67 and cytokeratin 19 expression in hepatocellular carcinoma: a systematic review and meta-analysis.

Background: Radiomics have been increasingly used in the clinical management of hepatocellular carcinoma (HCC), such as markers prediction. Ki-67 and cytokeratin 19 (CK-19) are important prognostic markers of HCC. Radiomics has been introduced by many researchers in the prediction of these markers expression, but its diagnostic value remains controversial. Therefore, this review aims to assess the diagnostic value of radiomics in predicting Ki-67 and CK-19 expression in HCC. Methods: Original studies were systematically searched in PubMed, EMBASE, Cochrane Library, and Web of Science from inception to May 2023. All included studies were evaluated by the radiomics quality score. The C-index was used as the effect size of the performance of radiomics in predicting Ki-67and CK-19 expression, and the positive cutoff values of Ki-67 label index (LI) were determined by subgroup analysis and meta-regression. Results: We identified 34 eligible studies for Ki-67 (18 studies) and CK-19 (16 studies). The most common radiomics source was magnetic resonance imaging (MRI; 25/34). The pooled C-index of MRI-based models in predicting Ki-67 was 0.89 (95% CI:0.86-0.92) in the training set, and 0.87 (95% CI: 0.82-0.92) in the validation set. The pooled C-index of MRI-based models in predicting CK-19 was 0.86 (95% CI:0.81-0.90) in the training set, and 0.79 (95% CI: 0.73-0.84) in the validation set. Subgroup analysis suggested Ki-67 LI cutoff was a significant source of heterogeneity (I 2 = 0.0% P>0.05), and meta-regression showed that the C-index increased as Ki-67 LI increased. Conclusion: Radiomics shows promising diagnostic value in predicting positive Ki-67 or CK-19 expression. But lacks standardized guidelines, which makes the model and variables selection dependent on researcher experience, leading to study heterogeneity. Therefore, standardized guidelines are warranted for future research. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023427953.

Markhor-derived Introgression of a Genomic Region Encompassing PAPSS2 Confers High-altitude Adaptability in Tibetan Goats.

Understanding the genetic mechanism of how animals adapt to extreme conditions is fundamental to determine the relationship between molecular evolution and changing environments. Goat is one of the first domesticated species and has evolved rapidly to adapt to diverse environments, including harsh high-altitude conditions with low temperature and poor oxygen supply but strong ultraviolet radiation. Here, we analyzed 331 genomes of domestic goats and wild caprid species living at varying altitudes (high > 3000 m above sea level and low < 1200 m), along with a reference-guided chromosome-scale assembly (contig-N50: 90.4 Mb) of a female Tibetan goat genome based on PacBio HiFi long reads, to dissect the genetic determinants underlying their adaptation to harsh conditions on the Qinghai-Tibetan Plateau (QTP). Population genomic analyses combined with genome-wide association studies (GWAS) revealed a genomic region harboring the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene showing strong association with high-altitude adaptability (PGWAS = 3.62 × 10-25) in Tibetan goats. Transcriptomic data from 13 tissues revealed that PAPSS2 was implicated in hypoxia-related pathways in Tibetan goats. We further verified potential functional role of PAPSS2 in response to hypoxia in PAPSS2-deficient cells. Introgression analyses suggested that the PAPSS2 haplotype conferring the high-altitude adaptability in Tibetan goats originated from a recent hybridization between goats and a wild caprid species, the markhor (Capra falconeri). In conclusion, our results uncover a hitherto unknown contribution of PAPSS2 to high-altitude adaptability in Tibetan goats on QTP, following interspecific introgression and natural selection.

Genome-wide association study for wattles trait in the dairy goat breed.

Dairy goats are significant livestock that provide high-quality milk sources in the world. The wattles trait is an evident phenotypic character on the neck of a dairy goat, which is considered to be under genetic control. We collected samples of 189 dairy goats, including 94 with wattles and 95 without wattles, from four different farms and multiple dairy goat breeds. The samples were genotyped with the GeneSeek Genomic Profiler Goat 70 K SNP chip. Genome-wide association studies (GWAS) in wattles have identified associations with single nucleotide polymorphisms (SNPs) at chromosome 10. In this area, an extremely strong association locus was assigned to FMN1 (Formin 1) belongs to the formin homology family and is associated with limb deformity, other candidate genes of interest confirmed for wattles were ARHGAP11A (Rho GTPase Activating Protein 11 A) and GJD2 (Gap Junction Protein Delta 2). Meanwhile, we found the presence or absence of wattles had no significant effect on milk yield. This research will provide genetic resources useful to explore genetic factors affecting the trait.

Boosting immunotherapy of triple negative breast cancer through the synergy of mild PTT and Fe-loaded organosilica nanoparticles.

Triple negative breast cancer (TNBC) is associated with drug resistance, metastasis, and poor immune response. The development of novel strategies to evoke a robust immune response against TNBC is necessary. In this study, we propose a TNBC tumor immunotherapy modality by synergizing nanocatalytic medicine with mild photothermal therapy. Briefly, mesoporous organosilica nanoparticles (MONs) and an Fe3+-loaded MON (MOF) were prepared. Then, the MOF was modified by hyaluronic acid (HA) and loaded with indocyanine green (ICG) to obtain MOFH (IMOFH). The IMOFH was spherical with a uniform particle size and showed pH-dependent Fe3+ release behavior. In vitro experiments showed that IMOFH was effectively internalized by 4T1 cells, which resulted in Fe3+-mediated oxidative cell death in synergy with mild PTT. Furthermore, this synergistic therapy activated dendritic cells (DCs) through damage-associated molecular pattern (DAMP) exposure resulting from enhanced oxidative damage in tumor cells. In vivo experiments showed that the application of mild PTT promoted IMOFH-mediated maturation of DCs and infiltration of CD8+ T cells. The synergistic effects of IMOFH and mild PTT resulted in boosted activation of adaptive immunity. The pH responsive nanocatalytic medicine IMOFH promoted significant adaptive immunity through the exposure of tumor associated antigens via the Fe3+ mediated Fenton reaction in concert with mild PTT. These effects resulted in the elimination of TNBC tumors without obvious side effects. Therefore, such a synergistic modality of IMOFH + mild PTT is promising for TNBC therapy.

Transmission of the gut microbiome in cohousing goats and pigs.

Social interaction facilitates the horizontal transmission of the microbiota between different individuals. However, little is known about the level of microbiota transmission in different livestock animals and different digestive tracts. The Hainan black goat and Wuzhishan pig are typical tropical local breeds on Hainan Island in China. Thus, we sampled and analyzed the gut microbiome in Hainan black goats (cecum and rumen) and Wuzhishan pigs (cecum) to study horizontal transmission by rearing them in the same pen (six goats and six pigs) or separate pens (nine goats and nine pigs). De novo assembly and binning recovered 3,262 strain-level and 2,488 species-level metagenome-assembled genomes (MAGs) using ∼1.3 Tb sequencing data. Of these MAGs, 1,856 MAGs were identified as novel strain. Compared with goats living in separate pens, social interaction in the same pen promotes community homogeneity in the rumen microbiome (P < 0.05) and the cecum microbiome (P < 0.05), respectively. Notably, approximately 7.08% (231/3262) of the gut microbial population could transmit during cohousing, 12 strains only in inter-species transmission, versus 190 strains only in intra-species transmission, and 10 strains only in foregut and hindgut transmission. In addition, the social contact group has high transmitted strain abundance, which is correlated with community composition. This study provided a new insight into the influence of social interaction on the animal gut microbiota.

Metagenomic Analysis of in Vitro Ruminal Fermentation Reveals the Role of the Copresent Microbiome in Plant Biomass Degradation.

In vitro ruminal fermentation is considered an efficient way to degrade crop residue. To better understand the microbial communities and their functions during in vitro ruminal fermentation, the microbiome and short chain fatty acid (SCFA) production were investigated using the metagenomic sequencing and rumen simulation technique (RUSITEC) system. A total of 1677 metagenome-assembled genomes (MAGs) were reconstructed, and 298 MAGs were found copresenting in metagenomic data of the current work and 58 previously ruminal representative samples. Additionally, the domains related to pectin and xylan degradation were overrepresented in the copresent MAGs compared with total MAGs. Among the copresent MAGs, we obtained 14 MAGs with SCFA-synthesis-related genes positively correlated with SCFA concentrations. The MAGs obtained from this study enable a better understanding of dominant microbial communities across in vivo and in vitro ruminal fermentation and show promise for pointing out directions for further research on in vitro ruminal fermentation.

Integrating Metabolomics and Network Analysis for Exploring the Mechanism Underlying the Antidepressant Activity of Paeoniflorin in Rats With CUMS-Induced Depression.

Background: Paeoniflorin (PF) represents the major bioactive constituent of the traditional Chinese medicine plant Paeonia suffruticosa (Ranunculaceae), which has a long history as a folk medicine in Asian. Paeoniflorin, a bitter pinene monoterpene glycoside, has antidepressant effects, but its potential therapeutic mechanism has not been thoroughly explored. Methods: Experimental depression in rats was established by the chronic unpredictable mild stress (CUMS) combined with orphan method, and the efficacy of paeoniflorin on depression was evaluated by the sucrose preference test and open field test. The antidepressant mechanism of paeoniflorin was investigated by metabolomic and network pharmacology. The relevant pathways of biomarkers highlighted in metabolomics were explored, and the possible targets of paeoniflorin in the treatment of depression were further revealed through network analysis. The binding activity of paeoniflorin to key targets was verified by molecular docking. Results: Metabolomics showed that rats with CUMS-induced depression had urine metabolic disorders, which were reversed by paeoniflorin through the regulation of metabolic pathways. Metabolites that play a key role in the function of paeoniflorin include citric acid, thiamine monophosphate, gluconolactone, 5-hydroxyindoleacetic acid and stachyose. Key predicted targets are SLC6A4, TNF, IL6 and SLC6A3. An important metabolic pathway is the Citrate cycle (TCA cycle). Conclusion: Network integrative analysis in this study showed that paeoniflorin could improve depressive-like symptoms in model rats with CUMS-induced depression and overall correct the disordered metabolic profile through multiple metabolic pathways.

Chinese herbal medicines in the treatment of ulcerative colitis: a review.

OBJECTIVE: To investigate how the ulcerative colitis (UC) be treated with Chinese herbal medicines (CHM), using Chinese medicine (CM) pattern (zheng) identification, in the current clinical practice. METHODS: A total of 7 electronic databases were systematically searched for UC clinical studies with CHM interventions (including single herbs and CHM formulas) published in English and Chinese from the date of their inception to November 25, 2020. Descriptive statistics were adopted to demonstrate the characteristics of study design, and to collate the commonly CM patterns of UC and frequently used CHM herbs and formulas. Further, IBM SPSS Modeler 18.0 and Cytoscape 3.7.1 software were used to analyze and visualize the associations between different categories of CHM and their zheng indications. RESULTS: A total of 2311 articles were included in this study, of which most (> 90%) were RCTs with CHM formulas. The most common zheng of UC was Large intestine dampness-heat, while the basic type of CM patten was Spleen deficiency. The most frequently used classical formula was Bai-Tou-Weng-Tang, followed by Shen-Ling-Bai-Zhu-San, and the commonly used proprietary CHM was Xi-Lei-San (enema). Sulfasalazine and Mesalazine are commonly used as concomitant western medicines. The most frequently used single medicinals were Huang Lian and Bai Zhu, which also identified as the core herbs for different CM patterns. CONCLUSION: This study examined the application of CHM interventions for UC and summarized their characteristics in clinical practice. These data indicated there were limited information about the safety assessment of CHM formulas and further RCTs including CM pattern(s) with strict design are necessary.

De Novo Assembly of 20 Chicken Genomes Reveals the Undetectable Phenomenon for Thousands of Core Genes on Microchromosomes and Subtelomeric Regions.

The gene numbers and evolutionary rates of birds were assumed to be much lower than those of mammals, which is in sharp contrast to the huge species number and morphological diversity of birds. It is, therefore, necessary to construct a complete avian genome and analyze its evolution. We constructed a chicken pan-genome from 20 de novo assembled genomes with high sequencing depth, and identified 1,335 protein-coding genes and 3,011 long noncoding RNAs not found in GRCg6a. The majority of these novel genes were detected across most individuals of the examined transcriptomes but were seldomly measured in each of the DNA sequencing data regardless of Illumina or PacBio technology. Furthermore, different from previous pan-genome models, most of these novel genes were overrepresented on chromosomal subtelomeric regions and microchromosomes, surrounded by extremely high proportions of tandem repeats, which strongly blocks DNA sequencing. These hidden genes were proved to be shared by all chicken genomes, included many housekeeping genes, and enriched in immune pathways. Comparative genomics revealed the novel genes had 3-fold elevated substitution rates than known ones, updating the knowledge about evolutionary rates in birds. Our study provides a framework for constructing a better chicken genome, which will contribute toward the understanding of avian evolution and the improvement of poultry breeding.

Efficacy and safety of Xiaoyao pills for mild to moderate depression: study protocol for a randomized controlled trial.

BACKGROUND: Depression is one of the most frequent and severe psychiatric conditions. Many chemical drugs to treat depression are associated with adverse reactions and have shortcomings. Traditional Chinese medicine is of great significance in the prevention and treatment of depression. Xiaoyao pills has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions. The aim of our study is to evaluate the efficacy and safety of Xiaoyao pills on mild to moderate depression patients. METHODS: This study is a multi-centre, double-blinded, randomized and placebo-controlled clinical trial. A total of 108 participants are assigned to three groups: Xiaoyao pill group taking Xiaoyao pills twice daily for 4 weeks, placebo group taking placebos twice daily for 4 weeks and normal group without taking any drug. The primary and secondary outcome measures are the Hamilton Depression Scale (HAMD) and Traditional Chinese Medicine (TCM) Syndrome Scale. The assessment is at baseline (before treatment initiation), 1 week, 2 weeks 4 weeks after the first treatment. Exploratory outcome is also assessed to explore the mechanism of Xiaoyao pills at baseline and 4 weeks. DISCUSSION: The results from this study will provide clinical evidence on the efficacy and safety of Xiaoyao pills in patients with mild to moderate depression with syndrome of liver stagnation and spleen deficiency. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN12746343. Registered on September 25, 2020.