Terpenoids from Alpinia galanga and their acetylcholinesterase inhibitory activity.

A new labdane diterpene (1), two new norsesquiterpenoids (2-3), as well as eight known terpenoids (4-11) were isolated from the seeds of Alpinia galanga (Zingiberaceae). Their structures and absolute configurations were elucidated by 1D, 2D NMR, MS, and comparison of their experimental and calculated electronic circular dichroism (ECD). The acetylcholinesterase (AChE) inhibitory activities of all the isolated compounds (1-11) were evaluated and the result showed that compounds 6 and 9 had inhibitory activity against AChE, with IC50 values at 295.70 and 183.91 µM, whereas other compounds did not show any inhibitory activity.

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis.

BACKGROUND: Hepatitis B cirrhosis (HBC) is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction. Although the relationship between certain single probiotics and HBC has been explored, the impact of the complex ready-to-eat Lactobacillus paracasei N1115 (LP N1115) supplement on patients with HBC has not been determined. AIM: To compare the changes in the microbiota, inflammatory factor levels, and liver function before and after probiotic treatment in HBC patients. METHODS: This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020. Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only. Fecal samples were collected at the onset and conclusion of the 12-wk intervention period. The structure of the intestinal microbiota and the levels of serological indicators, such as liver function and inflammatory factors, were assessed. RESULTS: Following LP N1115 intervention, the intestinal microbial diversity significantly increased in the intervention group (P < 0.05), and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria. Additionally, the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors (P < 0.05). CONCLUSION: LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota, improving liver function, and reducing inflammatory factor levels.

Gastrodin alleviates mitochondrial dysfunction by regulating SIRT3-mediated TFAM acetylation in vascular dementia.

BACKGROUND: Mitochondrial dysfunction is key to the pathogenesis of vascular dementia (VaD). Sirtuin-3 (SIRT3), an essential member of the sirtuins family, has been proven to be a critical sirtuin in regulating mitochondrial function. The phenolic glucoside gastrodin (GAS), a bioactive ingredient from Gastrodiae Rhizome (known in Chinese as Tian ma) demonstrates significant neuroprotective properties against central nervous system disorders; however, the precise mechanisms through which GAS modulates VaD remain elusive. PURPOSE: This study aims to investigate whether GAS confers a protective role against VaD, and to figure out the underlying molecular mechanisms. METHODS: A bilateral common carotid artery occlusion (BCCAO)-mediated chronic cerebral hypoperfusion (CCH) VaD rat model and a hypoxia model using HT22 cells were employed to investigate pharmacological properties of GAS in mitigating mitochondrial dysfunction. A SIRT3 agonist resveratrol (RES), a SIRT3 inhibitor 3-TYP and SIRT3-knockdown in vitro were used to explore the mechanism of GAS in association with SIRT3. The ability of SIRT3 to bind and deacetylate mitochondrial transcription factor A (TFAM) was detected by immunoprecipitation assay, and TFAM acetylation sites were further validated using mass spectrometry. RESULTS: GAS increased SIRT3 expression and ameliorated mitochondrial structure, mitochondrial respiration, mitochondrial dynamics along with upregulated TFAM, mitigating oxidative stress and senescence. Comparable results were noted with the SIRT3 agonist RES, indicating an impactful neuroprotection played by SIRT3. Specifically, the attenuation of SIRT3 expression through knockdown techniques or exposure to the SIRT3 inhibitor 3-TYP in HT22 cells markedly abrogated GAS-mediated mitochondrial rescuing function. Furthermore, our findings elucidate a novel facet: SIRT3 interacted with and deacetylated TFAM at the K5, K7, and K8 sites. Decreased SIRT3 is accompanied by hyper-acetylated TFAM. CONCLUSION: The present results were the first to demonstrate that the SIRT3/TFAM pathway is a protective target for reversing mitochondrial dysfunction in VaD. The findings suggest that GAS-mediated modulation of the SIRT3/TFAM pathway, a novel mechanism, could ameliorate CCH-induced VaD, offering a potentially beneficial therapeutic strategy for VaD.

Role and Mechanism of Epigenetic Regulation in the Aging of Germ Cells: Prospects for Targeted Interventions.

In modern times, a notable trend toward delayed childbearing has been observed in most developed countries. As a result, sperm aging and quality loss, as well as premature ovarian failure (POF), have emerged as major causes of infertility. The pathogenesis of sperm aging and POF is complex and has not been clearly elucidated. However, evidence from some studies has linked germ cell aging to epigenetic modifications. Epigenetics refers to the heritable changes in gene expression that occur in the absence of any alterations to the gene's nucleotide sequence. This paper systematically reviewed and analyzed the relevant literature to describe the relationship of DNA methylation, non-coding RNA regulation, histone modifications, chromatin remodeling, and RNA modifications with sperm aging and POF. In addition, we analyzed how sperm aging and POF can be mitigated via epigenetic interventions. This review could provide new therapeutic insights and guide strategies for improving sperm quality and ovarian function.

Using scanning electron microscopy and molecular data to discover a new species from old herbarium collections: The case of Phlomoideshenryi (Lamiaceae, Lamioideae).

Phlomoides is one of the largest genera of Lamiaceae with approximately 150-170 species distributed mainly in Eurasia. In this study, we describe and illustrate a new species, P.henryi, which was previously misidentified as P.bracteosa, from Yunnan Province, southwest China. Molecular phylogenetic analyses revealed that P.henryi is found within a clade in which most species lack basal leaves. In this clade, the new species is morphologically distinct from P.rotata in having an obvious stem and, from the rest, by having transparent to white trichomes inside the upper corolla lip. In addition, micro-features of trichomes on the calyx and leaf epidermis can differentiate the new species from other species grouped in the same clade and a key, based on trichome morphology for these species, is provided. The findings demonstrate that the use of scanning electron microscopy can reveal inconspicuous morphological affinities amongst morphologically similar species and play an important role in the taxonomic study of the genus Phlomoides.

Isodonxiaoluzhiensis (Lamiaceae, Nepetoideae), a new species from Yunnan, southwest China.

Isodonxiaoluzhiensis, a new species of the tribe Ocimeae in family Lamiaceae, is described and illustrated. The new species is known only from the type locality, Xiaoluzhi village in Luzhijang dry-hot valley of Yimen County, central Yunnan, southwest China. It is characterized by having a procumbent habit, gracile stems and branches, relatively small leaves and flowers, and the phenology of flowering in winter. The morphological comparisons with its putative closest relatives (I.adenanthus and I.hsiwenii) are also presented.

miR-199a/b-3p inhibits HCC cell proliferation and invasion through a novel compensatory signaling pathway DJ-1\Ras\PI3K/AKT.

Several studies have reported the effects of DJ-1 gene and miR-199a/b-3p on HCC development. However, whether miR-199a/b-3p regulates HCC progression through a novel compensatory signaling pathway involving DJ-1, Ras, and PI3K/AKT remains unknown. We used (TCGA, HPA, miRWalk and Target scan) databases, cancer and para-tissue HCC patients, dual-luciferase reporter gene analysis, proteomic imprinting, qPCR, cell proliferation, scratch, transport, and flow cytometry to detect the molecular mechanism of DJ-1 and miR-199a/b-3p co-expression in HCC cell lines. Bioinformatics analysis showed that DJ-1 was highly expressed in HCC ((P < 0.001) were closely associated with tumor stage (T), portal vein vascular invasion, OS, DSS, and PFI (P < 0.05); miR-199a/b-3p was lowly expressed in HCC (P < 0.001), which was the upstream regulator of DJ-1. Spearman coefficient r = -0.113, P = 0.031; Dual luciferase gene report verified the negative targeting relationship between them P< 0.001; Western blotting demonstrated that miR-199a/b-3p could inhibit the protein expression of DJ-1, Ras and AKT(P < 0.05); The results of CCK8, cell scratch, Transwell migration and flow cytometry showed that OE + DJ-1 increased the proliferation, migration and invasion ability of HepG2 cells, and decreased the apoptosis process, and the differences were statistically significant (P < 0.05), while miR-199a/b-3p had the opposite effect (P < 0.05).

Essential oil from Fructus Alpinia zerumbet ameliorates atherosclerosis by activating PPARγ-LXRα-ABCA1/G1 signaling pathway.

BACKGROUND: Atherosclerosis (AS) is a progressive chronic disease. Currently, cardiovascular diseases (CVDs) caused by AS is responsible for the global increased mortality. Yanshanjiang as miao herb in Guizhou of China is the dried and ripe fruit of Fructus Alpinia zerumbet. Accumulated evidences have confirmed that Yanshanjiang could ameliorate CVDs, including AS. Nevertheless, its effect and mechanism on AS are still largely unknown. PURPOSE: To investigate the role of essential oil from Fructus Alpinia zerumbet (EOFAZ) on AS, and the potential mechanism. METHODS: A high-fat diet (HFD) ApoE-/- mice model of AS and a oxLDL-induced model of macrophage-derived foam cells (MFCs) were reproduced to investigate the pharmacological properties of EOFAZ on AS in vivo and foam cell formation in vitro, respectively. The underlying mechanisms of EOFAZ were investigated using Network pharmacology and molecular docking. EOFAZ effect on PPARγ protein stability was measured using a cellular thermal shift assay (CETSA). Pharmacological agonists and inhibitors and gene interventions were employed for clarifying EOFAZ's potential mechanism. RESULTS: EOFAZ attenuated AS progression in HFD ApoE-/- mice. This attenuation was manifested by the reduced aortic intima plaque development, increased collagen content in aortic plaques, notable improvement in lipid profiles, and decreased levels of inflammatory factors. Moreover, EOFAZ inhibited the formation of MFCs by enhancing cholesterol efflux through activiting the PPARγ-LXRα-ABCA1/G1 pathway. Interestingly, the pharmacological knockdown of PPARγ impaired the beneficial effects of EOFAZ on MFCs. Additionally, our results indicated that EOFAZ reduced the ubiquitination degradation of PPARγ, and the chemical composition of EOFAZ directly bound to the PPARγ protein, thereby increasing its stability. Finally, PPARγ knockdown mitigated the protective effects of EOFAZ on AS in HFD ApoE-/- mice. CONCLUSION: These findings represent the first confirmation of EOFAZ's in vivo anti-atherosclerotic effects in ApoE-/- mice. Mechanistically, its chemical constituents can directly bind to PPARγ protein, enhancing its stability, while reducing PPARγ ubiquitination degradation, thereby inhibiting foam cell formation via activation of the PPARγ-LXRα-ABCA1/G1 pathway. Simultaneously, EOFAZ could ameliorates blood lipid metabolism and inflammatory microenvironment, thus synergistically exerting its anti-atherosclerotic effects.

Generation of Human Blood Vessel and Vascularized Cerebral Organoids.

Brain organoids have been widely used to study diseases and the development of the nervous system. Many reports have investigated the application of brain organoids, but most of these models lack vascular structures, which play essential roles in brain development and neurological diseases. The brain and blood vessels originate from two different germ layers, making it difficult to induce vascularized brain organoids in vitro. We developed this protocol to generate brain-specific blood vessel and cerebral organoids and then fused them at a specific developmental time point. The fused cerebral organoids exhibited robust vascular network-like structures, which allows simulating the in vivo developmental processes of the brain for further applications in various neurological diseases. Key Features • Culturing vascularized brain organoids using human embryonic stem cells (hESCs). • The new approach generates not only neural cells and vessel-like networks but also brain-resident microglia immune cells in a single organoid.

A Unique G-Quadruplex Aptamer: A Novel Approach for Cancer Cell Recognition, Cell Membrane Visualization, and RSV Infection Detection.

Surface staining has emerged as a rapid technique for applying external stains to trace cellular identities in diverse populations. In this study, we developed a distinctive aptamer with selective binding to cell surface nucleolin (NCL), bypassing cytoplasmic internalization. Conjugation of the aptamer with a FAM group facilitated NCL visualization on live cell surfaces with laser confocal microscopy. To validate the aptamer-NCL interaction, we employed various methods, including the surface plasmon resonance, IHC-based flow cytometry, and electrophoretic mobility shift assay. The G-quadruplex formations created by aptamers were confirmed with a nuclear magnetic resonance and an electrophoretic mobility shift assay utilizing BG4, a G-quadruplex-specific antibody. Furthermore, the aptamer exhibited discriminatory potential in distinguishing between cancerous and normal cells using flow cytometry. Notably, it functioned as a dynamic probe, allowing real-time monitoring of heightened NCL expression triggered by a respiratory syncytial virus (RSV) on normal cell surfaces. This effect was subsequently counteracted with dsRNA transfection and suppressed the NCL expression; thus, emphasizing the dynamic attributes of the probe. These collective findings highlight the robust versatility of our aptamer as a powerful tool for imaging cell surfaces, holding promising implications for cancer cell identification and the detection of RSV infections.

Functional divergence of CYP76AKs shapes the chemodiversity of abietane-type diterpenoids in genus Salvia.

The genus Salvia L. (Lamiaceae) comprises myriad distinct medicinal herbs, with terpenoids as one of their major active chemical groups. Abietane-type diterpenoids (ATDs), such as tanshinones and carnosic acids, are specific to Salvia and exhibit taxonomic chemical diversity among lineages. To elucidate how ATD chemical diversity evolved, we carried out large-scale metabolic and phylogenetic analyses of 71 Salvia species, combined with enzyme function, ancestral sequence and chemical trait reconstruction, and comparative genomics experiments. This integrated approach showed that the lineage-wide ATD diversities in Salvia were induced by differences in the oxidation of the terpenoid skeleton at C-20, which was caused by the functional divergence of the cytochrome P450 subfamily CYP76AK. These findings present a unique pattern of chemical diversity in plants that was shaped by the loss of enzyme activity and associated catalytic pathways.

East Asian-North American disjunctions and phylogenetic relationships within subtribe Nepetinae (Lamiaceae).

Biogeographic disjunctions, including intercontinental disjunctions, are frequent across plant lineages and have been of considerable interest to biologists for centuries. Their study has been reinvigorated by molecular dating and associated comparative methods. One of the "classic" disjunction patterns is that between Eastern Asia and North America. It has been speculated that this pattern is the result of vicariance following the sundering of a widespread Acrto-Teritary flora. Subtribe Nepetinae in the mint family (Lamiaceae) is noteworthy because it contains three genera with this disjunction pattern: Agastache, Dracocephalum, and Meehania. These disjunctions are ostensibly the result of three separate events, allowing for concurrent testing of the tempo, origin, and type of each biogeographic event. Using four plastid and four nuclear markers, we estimated divergence times and analyzed the historical biogeography of Nepetinae, including comprehensive sampling of all major clades for the first time. We recover a well-supported and largely congruent phylogeny of Nepetinae between genomic compartments, although several cases of cyto-nuclear discordance are evident. We demonstrate that the three disjunctions are pseudo-congruent, with unidirectional movement from East Asia at slightly staggered times during the late Miocene and early Pliocene. With the possible exception of Meehania, we find that vicariance is likely the underlying driver of these disjunctions. The biogeographic history of Meehania in North America may be best explained by long-distance dispersal, but a more complete picture awaits deeper sampling of the nuclear genome and more advanced biogeographical models.

Gastrodin relieves cognitive impairment by regulating autophagy via PI3K/AKT signaling pathway in vascular dementia.

Vascular dementia (VaD), the second most common type of dementia, is attributed to lower cerebral blood flow. To date, there is still no available clinical treatment for VaD. The phenolic glucoside gastrodin (GAS) is known for its neuroprotective effects, but the role and mechanisms of action on VD remains unclear. In this study, we aim to investigate the neuroprotective role and underlying mechanisms of GAS on chronic cerebral hypoperfusion (CCH)-mediated VaD rats and hypoxia-induced injury of HT22 cells. The study showed that GAS relieved learning and memory deficits, ameliorated hippocampus histological lesions in VaD rats. Additionally, GAS down-regulated LC3II/I, Beclin-1 levels and up-regulated P62 level in VaD rats and hypoxia-injured HT22 cells. Notably, GAS rescued the phosphorylation of PI3K/AKT pathway-related proteins expression, which regulates autophagy. Mechanistic studies verify that YP-740, a PI3K agonist, significantly resulted in inhibition of excessive autophagy and apoptosis with no significant differences were observed in the YP-740 and GAS co-treatment. Meantime, we found that LY294002, a PI3K inhibitor, substantially abolished GAS-mediated neuroprotection. These results revealed that the effects of GAS on VaD are related to stimulating PI3K/AKT pathway-mediated autophagy, suggesting a potentially beneficial therapeutic strategy for VaD.

Unveiling the role of G-quadruplex structure in promoter region: Regulation of ABCA1 expression in macrophages possibly via NONO protein recruitment.

ABCA1 has been found to be critical for cholesterol efflux in macrophages. Understanding the mechanism regulating ABCA1 expression is important for the prevention and treatment of atherosclerosis. In the present study, a G-quadruplex (G4) structure was identified in the ABCA1 promoter region. This G4 was shown to be essential for ABCA1 transcription. Stabilizing the G4 by ligands surprisingly upregulated ABCA1 expression in macrophages. Knocking out the G4 remarkably reduced ABCA1 expression, and abolished the increase of ABCA1 expression induced by the G4 ligand. By pull-down assays, the protein NONO was identified as an ABCA1 G4 binder. Overexpression or repression of NONO significantly induced upregulation and downregulation of ABCA1 expression, respectively. ChIP and EMSA experiments showed that the G4 ligand promoted the binding between the ABCA1 G4 and NONO, which led to more recruitment of NONO to the promoter region and enhanced ABCA1 transcription. Finally, the G4 ligand was shown to significantly reduce the accumulation of cholesterol in macrophages. This study showed a new insight into the regulation of gene expression by G4, and provided a new molecular mechanism regulating ABCA1 expression in macrophages. Furthermore, the study showed a possible novel application of the G4 ligand: preventing and treating atherosclerosis.

Seed morphology of Hypericum (Hypericaceae) in China and its taxonomic significance.

The seed morphology of 40 taxa within the genus Hypericum (Hypericaceae) from China, representing 9 sections of the genus, was examined using both Light and Scanning Electron Microscopy to evaluate the taxonomic relevance of macro- and micro-morphological features. Details articulating variation in seed size, color, shape, appendages, and seed coat ornamentation are described, illustrated, and compared, and their taxonomic importance is discussed. Seeds were generally brown in color and cylindric-ellipsoid to prolonged cylindric in shape. Seed size displayed wide variation, ranging from 0.37-1.91 mm in length and 0.12-0.75 mm in width. Seed appendages were observed as a characteristic morphological feature. Seed surface ornamentation has high phenotypic plasticity, and four types (reticulate, foveolate, papillose, and ribbed) can be recognized. In general, seed color and shape have limited taxonomic significance. However, some other features represent informative characters that can be used efficiently in distinguishing the studied taxa at the section and/or species levels. The findings illustrate that considerable taxonomic knowledge can be obtained by investigating the seed features of Hypericum, and the use of Scanning Electron Microscopy can reveal inconspicuous morphological affinities among species and play a role in taxonomic and systematic studies of the genus Hypericum. RESEARCH HIGHLIGHTS: Macro- and micro-morphological features of seeds of 40 Hypericum taxa from China were examined using Light and Scanning Electron Microscopy, providing the first broad study regarding seed morphology for Hypericum from China. Details and variations of seed size, shape, color, surface ornamentation, and appendages are fully presented. Seed features and their variation have important taxonomic significance at the section and/or species levels within Hypericum.

Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB.

Rheumatoid arthritis (RA) is a chronic autoimmune disease triggered by a cascading inflammatory response. Sigesbeckia Herba (SH) has long been utilized as a traditional remedy to alleviate symptoms associated with rheumatism. Our previous study found that leocarpinolide B (LB), a sesquiterpene lactone isolated from the whole plant of SH, possesses potent a anti-inflammatory effect on macrophages. This study was designed to evaluate the therapeutic effects of LB on RA, and further investigate the underlying mechanisms. In collagen type II-induced arthritic mice, LB was demonstrated to decrease the production of autoimmune antibodies in serum and inflammatory cytokines in the joint muscles and recover the decreased regulatory T lymphocytes in spleen. Moreover, LB significantly suppressed the inflammatory infiltration, formation of pannus and bone erosion in the paw joints. In vitro testing showed that LB inhibited the proliferation, migration, invasion, and secretion of inflammatory cytokines in IL-1ß-induced human synovial SW982 cells. Network pharmacology and molecular docking suggested NF-κB p65 could be the potential target of LB on RA treatment, subsequent experimental investigation confirmed that LB directly interacted with NF-κB p65 and reduced the DNA binding activity of NF-κB in synovial cells. In conclusion, LB significantly attenuated the collagen type II-induced arthritis, which was at least involved in the inhibition of DNA binding activity of NF-κB through a direct binding to NF-κB p65. These findings suggest that LB could be a valuable lead compound for developing anti-RA drugs.

Diversity, morphology, and molecular phylogeny of Diatrypaceae from southern China.

During an investigation of Diatrypaceae from southern China, 10 xylariales-like taxa have been collected. Morphological and multi-gene analyses confirmed that these taxa reside in Diatrypaceae and represent eight novel taxa and two new records belonging to six genera (viz., Allocryptovalsa, Diatrype, Diatrypella, Paraeutypella, Peroneutypa, and Vasilyeva gen. nov.). Vasilyeva gen. nov. was proposed to accommodate Vasilyeva cinnamomi sp. nov. Among the other collections, seven new species were introduced (viz., Diatrype camelliae-japonicae sp. nov., Diatrype rubi sp. nov., Diatrypella guiyangensis sp. nov., Diatrypella fatsiae-japonicae sp. nov., Paraeutypella subguizhouensis sp. nov., Peroneutypa hainanensis sp. nov., and Peroneutypa qianensis sp. nov.), while two were reported as new records from China (Allocryptovalsa rabenhorstii and Diatrype enteroxantha). For Diatrypaceae, the traditional taxonomic approach based on morphology may not be applicable.

Site-directed mutagenesis identified the key active site residues of 2,3-oxidosqualene cyclase HcOSC6 responsible for cucurbitacins biosynthesis in Hemsleya chinensis.

Hemsleya chinensis is a Chinese traditional medicinal plant, containing cucurbitacin IIa (CuIIa) and cucurbitacin IIb (CuIIb), both of which have a wide range of pharmacological effects, including antiallergic, anti-inflammatory, and anticancer properties. However, few studies have been explored on the key enzymes that are involved in cucurbitacins biosynthesis in H. chinensis. Oxidosqualene cyclase (OSC) is a vital enzyme for cyclizing 2,3-oxidosqualene and its analogues. Here, a gene encoding the oxidosqualene cyclase of H. chinensis (HcOSC6), catalyzing to produce cucurbitadienol, was used as a template of mutagenesis. With the assistance of AlphaFold2 and molecular docking, we have proposed for the first time to our knowledge the 3D structure of HcOSC6 and its binding features to 2,3-oxidosqualene. Mutagenesis experiments on HcOSC6 generated seventeen different single-point mutants, showing that single-residue changes could affect its activity. Three key amino acid residues of HcOSC6, E246, M261 and D490, were identified as a prominent role in controlling cyclization ability. Our findings not only comprehensively characterize three key residues that are potentially useful for producing cucurbitacins, but also provide insights into the significant role they could play in metabolic engineering.

Study on detection of CNVs using human whole genome bisulfite sequencing data.

It has been reported that the aberrant DNA methylation may result in copy number variations (CNVs), and the CNVs may alter the levels of DNA methylation. Whole genome bisulfite sequencing (WGBS) is able to generate the sequencing data of DNAs, and shows the potential ability to detect CNVs. However, the evaluations and performances on the detections of CNVs using WGBS data is still unclear. In this study, five software with different strategies for CNV detections, e.g., BreakDancer, cn.mops, CNVnator, DELLY and Pindel, were selected to explore and benchmark the performances of CNV detections with WGBS data. Based on the real (2.62 billion reads) and simulated (12.35 billion reads) WGBS data of humans, we calculated the number, precision, recall, relative ability, memory usage, and running time of CNV detections by 150 times, and tried to figure out the optimal strategy for CNV detections with WGBS data. Based on the real WGBS data, Pindel detected the most deletions and duplications, CNVnator detected the deletions with the highest precision, cn.mops detected the duplications with the highest precision, Pindel detected the deletions with the highest recall, and cn.mops detected the duplications with the highest recall. Based on the simulated WGBS data, BreakDancer detected the most deletions, and cn.mops detected the most duplications. The CNVnator showed the highest precision and recall for both deletions and duplications. In real and simulated WGBS data, the ability of CNVnator to detect CNVs was likely to overtake that in the whole genome sequencing data. Additionally, DELLY and BreakDancer displayed the lowest peak of memory usage and the lest CPU runtime, while CNVnator expressed the highest peak of memory usage and the most CPU runtime. Taken together, CNVnator and cn.mops showed the excellent performances of CNV detections with WGBS data. These results suggested that it was feasible to detect CNVs using WGBS data, and provided the useful information to further investigate both CNVs and DNA methylation using WGBS data alone.

Whether the Golgi protein 73 could be a diagnostic serological marker in hepatocellular carcinoma: a meta analysis.

BACKGROUND: The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis. METHODS: 36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software. RESULTS: The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74-0.83),0.85(95%CI 0.80-0.89),5.4(95%CI 3.8-7.5), 0.25(95%CI 0.20-0.31), 22(95%CI 13-35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64-0.81),0.70(95%CI 0.49-0.85),2.40(95%CI 1.3-4.7),0.38(95%CI 0.23-0.61),6(95%CI 2-19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis. CONCLUSION: The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.