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A small GTPase, RhoA, plays a variety of functions in the regulation of cellular and developmental events via its downstream effectors, including cytokinesis, cell migration, and phagocytosis. In this study, a novel RhoA-related gene from the planarian Dugesia japonica, DjRhoA, was cloned and characterized. The full-length cDNA of DjRhoA is 869 bp, and the open reading frame encodes a poly-peptide of 194 amino acids. Phylogenetic analysis revealed that DjRhoA clustered with another RhoA-related protein, DjRho2, and located on the base of phylogenetic tree. Whole-mount in situ hybridization results indicated that DjRhoA was expressed in the brain primordia and intestine during regeneration. Knockdown of DjRhoA induces defects in the brain and intestine. These results suggested that DjRhoA was responsible for the regeneration of brain and intestine in Dugesia japonica.

The growth and differentiation of neurons are critical events in the establishment of proper neuron connectivity and function. Planarians have a remarkable ability to completely regenerate a functional nervous system from a pluripotent stem cell population. Thus, planarians provide a powerful model to identify genes required for neuronal differentiation in vivo. The Wnt/Ca2+ signaling pathway is crucial for cancer development, arousing inflammatory responses, and neurodegeneration. We analyzed the expression patterns and RNAi phenotypes for members of the Wnt/Ca2+ signaling pathway in the planarian, Dugesia japonica. The expression of DjWnt5a, DjPLC-β, DjCamKII, and DjCaln during regeneration was surprisingly similar and revealing in the regenerated brain. RNAi knockdown of DjWnt5a, DjPLC-β, DjCamKII, and DjCaln led to defects in regenerated brains including brain partial deletions, incompact phenotypes at the posterior of the new brain, and lateral branches, which could not regenerate. Furthermore, the expressions of GAD and the number of GABAergic neurons decreased. Together, these results suggest that the Wnt/Ca2+ signaling pathway is required for GABAergic neuron regeneration.

The relationships between interleukin (IL)-6 and cardiac myxoma remain to be clarified. This article systematically reviewed the IL-6 properties in cardiac myxoma patients based on retrieval of pertinent literature published between 1998 and 2018. Significant differences were found in circulating IL-6 values between preoperation and 1 and 6 months after operation. Preoperative circulating IL-6 correlated significantly with tumour volume (r=0.8552, p=0.003), while there were no significant correlations with maximal tumour dimension (r=0.2443, p=0.190). No correlation was found between circulating IL-6 at 1 and 6 months after tumour resection with either tumour volume or with maximal tumour dimension. The positive rate of immunostaining of IL-6 in cardiac myxoma tissues was 93.3%. Overproduction of IL-6 is responsible for the inflammatory presentations, constitutional symptoms, and recurrence and distal embolisation of cardiac myxoma. Cardiac myxoma could be a cellular source of IL-6 release. Cardiac myxoma resection is an absolute choice of eliminating IL-6 production in these patients. Key Words: Cardiac surgical procedures, Cytokines; Inflammation, Interleukin-6, Neoplasms.

Anthocyanins are a type of natural pigment that have high potential for development and utilization in regions like food, pharmaceutical, and cosmetic industries, with nitrogen and phosphorus starvation possibly promoting their accumulation in grapes. However, it remains unclear whether such starvation impacts the grape callus, or how the co-starvation of nitrogen and phosphorus affects the biosynthesis of anthocyanins. Here, we investigated how nitrogen starvation, phosphorus starvation, and the co-starvation of these two elements affects the synthesis of anthocyanins in the callus of grape skin. Results showed that separate starvation of nitrogen and phosphorus, as well as nitrogen and phosphorus co-starvation, inhibited callus growth, while significantly promoting the accumulation of anthocyanins. However, co-starvation did not facilitate anthocyanin biosynthesis during the later stages of callus growth. qRT-PCR analysis showed that the expression of VvUFGT and VvMYBA1 was closely related to anthocyanin accumulation in the callus under nitrogen and phosphorus starvation. Besides, we also confirmed that the abscisic acid signaling pathway was involved in anthocyanin accumulation as well as callus resistance under adverse conditions. This study provides a basis for investigating the regulatory mechanisms of anthocyanin synthesis in grapes, as well as theoretical support for the production of anthocyanins by callus culture. Even though nitrogen and phosphorus deficiencies have been reported to promote anthocyanin biosynthesis in grapevine berries, whether the same deficiencies also induce anthocyanin accumulation in grape callus and whether nitrogen and phosphorus co-deficiency enhances this induction have yet to be reported. Therefore, the present study to investigate the effects of nitrogen starvation, phosphorus starvation, and nitrogen and phosphorus co-starvation on anthocyanin accumulation and ABA signaling in grape callus.

Human Y-chromosome haplogroup C2b-F1067 is one of the dominant paternal lineages of populations in Eastern Eurasia. In order to explore the origin, diversification, and expansion of this haplogroup, we generated 206 new Y-chromosome sequences from C2b-F1067 males and coanalyzed 220 Y-chromosome sequences of this haplogroup. BEAST software was used to reconstruct a revised phylogenetic tree of haplogroup C2b-F1067 with age estimates. The revised phylogeny of C2b-F1067 included 155 sublineages, 1986 non-private variants, and >6000 private variants. The age estimation suggested that the initial splitting of C2b-F1067 happened at about 32.8 thousand years ago (kya) and the major sublineages of this haplgroup experienced continuous expansion in the most recent 10,000 years. We identified numerous sublineages that were nearly specific for Korean, Mongolian, Chinese, and other ethnic minorities in China. In particular, we evaluated the candidate-specific lineage for the Dayan Khan family and the Confucius family, the descendants of the ruling family of the Chinese Shang dynasty. These findings suggest that ancient populations with varied C2b-F1067 sublineages played an important role during the formation of most modern populations in Eastern Eurasia, and thus eventually became the founding paternal lineages of these populations.

Background: Due to their long history, complex admixture processes and large population sizes, more research is required to explore the fine genetic structure of Han populations from different geographic locations of China.Aim: To characterise the paternal genetic structure of the Han Chinese in Henan province, which was once the central living region of the ancient Huaxia population, the precursors of the Han Chinese.Subjects and methods: We sequenced Y chromosomes of 60 males from Zhengzhou, Henan Province, and reconstructed a phylogenetic tree for these samples with age estimation.Results: We observed high diversity of paternal lineages in our collection. We found that the in situ Neolithic expansion of the "Major lineages" contributed to a large portion of the paternal gene pool of the Han population in Henan Province. We also detected a large number of "Minor lineages" that diverged in the Palaeolithic Age.Conclusion: We suggest that the high genetic diversity in the paternal gene pool of modern Han populations is mainly attributed to the reservation of a larger number of lineages that diverged in the Palaeolithic Age, while the recent expansion of limited lineages contributed to the majority of the gene pool of modern Han populations. We propose that such a structure is a basal characteristic for the genetic structure of modern Han populations.

To observe the effects of electroacupuncture (EA) of different frequencies on transmission function, electromyography, nitric oxide synthase (NOS) content and interstitial cells of Cajal (ICC) expression of colon in rat models with slow transit constipation (STC). Of the 50 healthy male Wistar rats, 10 were randomly selected as a normal group and fed with ordinary diet, and the remaining 40 rats were fed with the diet added with the compound diphenoxylate at a dose of 8 mg/(kg·bw) each day for continuous 120 d. The 40 successfully established STC rat models were randomly divided into a model group, a low-frequency EA group (2 Hz), a high-frequency EA group (100 Hz), and a variable-frequency EA group (2 Hz/100 Hz), with 10 rats in each group. Rats in the normal and the model groups were not given any treatment; the low-frequency EA and the high-frequency EA groups were given EA at Tianshu (ST 25), Zusanli (ST 36) and Zhigou (TE 6) with continuous wave at the designated frequency, and the variable-frequency EA group received sparse-dense wave (2 Hz/100 Hz) EA at the same acupoints, once a day for a total of 15 d. After treatment, the colonic transmission function, electromyography, NOS content and ICC expression (calculated by the difference in the area of the C-kit positive cells) of the rats in each group were measured. For the colonic transmission function, compared with the normal group, the first black stool excretion durations of rats in the other groups were significantly prolonged (all P

Fluorouracil (5-FU) and oxaliplatin (L-OHP) are the most commonly used chemotherapy drugs for colorectal cancer, though resistance is common. Compound Sophora injection is a traditional Chinese medicine that can protect the liver against oxidation, improve immunity, and enhance sensitivity to chemotherapy; it may have an effect of reversing resistance in 5-FU- and L-OHP-resistant gastric cancer cells (5-FU/SW480 and L-OHP/SW480, respectively). A concentration gradient experiment was performed to identify a nontoxic dose of compound Sophora injection. 5-FU/SW480 and L-OHP/SW480 cells were treated with the nontoxic dose of compound radix Sophorae injection for 48 h, and changes in drug resistance to 5-FU and L-OHP were detected. Alterations in apoptosis and the cell cycle were assessed, as were the mRNA and protein levels of permeability glycoprotein (P-gp), annexin A1 (ANXA1), and ATP-binding cassette superfamily G member 2 (ABCG2). Flow cytometry showed a reduction in the number of cells in the G1 phase and an increase of cells in the S phase (P<0.05). mRNA and protein expression of P-gp and ABCG2 was significantly higher in 5-FU/SW480 and L-OHP/SW480 cell lines, and ANXA1 expression decreased significantly (P<0.05). Compound Sophora injection can reverse the drug resistance of 5-FU/SW480 and L-OHP/SW480 cell lines to 5-FU and L-OHP, respectively, possibly through a mechanism involving reduced expression of P-gp and ABCG2 but enhanced expression of ANXA1, which is the basis for the identification of clinical drug resistance in colorectal cancer.

Intracontinental biotic divisions across the vast Palaearctic region are not well-characterized. Past research has revealed patterns ranging from a lack of population structure to deep divergences along varied lines of separation. Here we compared biogeographic patterns of two Palaearctic shorebirds with different habitat preferences, Whimbrel (Numenius phaeopus) and Eurasian curlew (N. arquata). Using genome-wide markers from populations across the Palaearctic, we applied a multitude of population genomic and phylogenomic approaches to elucidate population structure. Most importantly, we tested for isolation by distance and visualized barriers and corridors to gene flow. We found shallow Palaearctic population structure in subpolar bog and tundra-breeding whimbrels, consistent with other species breeding at a similarly high latitude, indicating connectivity across the tundra belt, both presently and during southward shifts in periods of global cooling. In contrast, the temperate grassland-breeding Eurasian curlew emerged in three distinct clades corresponding to glacial refugia. Barriers to gene flow coincided with areas of topographic relief in the central Palaearctic for whimbrels and further east for Eurasian curlews. Our findings highlight the interplay of historic and ecological factors in influencing present-day population structure of Palaearctic biota.

Antarctic krill (Euphausia superba) is one of the important bioresources in Antarctic waters, containing many bioactives (e.g., astaxanthin), which have a highly potential value for commercial exploitation. In this study, the effects of processing methods on the content, structural isomers, and composition of astaxanthins (free astaxanthin and astaxanthin esters) were studied. Three drying methods, comprising freeze-drying, microwave drying, and hot-air drying, were used. Free astaxanthin (Ast), astaxanthin monoesters (AM), and astaxanthin diesters (AD) in boiled krill (control) and dried krill were extracted and analyzed using high-resolution mass spectrometry with ultraviolet detection. After the three processes, total astaxanthin loss ranged from 8.6 to 64.9%, and the AM and AD contents ranged from 78.3 to 16.6 and 168.7 to 90.5 μg/g, respectively. Compared to other kinds of astaxanthin esters, astaxanthin esters, which linked to eicosapentaenoic acid and docosahexaenoic acid, as well as the Ast, were more easily degraded, and AM was more susceptible to degradation than AD. All-E-astaxanthin easily transformed to the 13Z-astaxanthin than to the 9Z-astaxanthin during the drying process, but the proportions of optical isomers changed due to drying by no more than 5%. The results suggested that freeze-drying, low-power microwave drying (≤1 kW), and low-temperature hot-air drying (≤60 °C) are optimal drying methods for ensuring the quality of krill products.

Obesity is considered a chronic inflammatory disease, the inflammatory factors, such as interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and small inducible cytokine A5 (RANTES), are elevated in obese individuals. Pituitary adenylate cyclase‐activating polypeptide (PACAP) suppresses anti‐inflammatory cytokines and ameliorates glucose and lipid metabolism. Our previous study showed that Fas apoptosis inhibitory molecule (FAIM) is a new mediator of Akt2 signalling, increases the insulin signalling pathway and lipid metabolism. In this study, we found that PACAP promoted the expression of FAIM protein in a human hepatocyte cell line (L02). Overexpression of FAIM with lentivirus suppressed the expression of the inflammatory factor interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and tumour necrosis factor alpha (TNF‐α). Following treatment of obese mice with FAIM or PACAP for 2 weeks, inflammation was alleviated and the bodyweight and blood glucose levels were decreased. Overexpression of FAIM down‐regulated the expression of adipogenesis proteins, including SREBP1, SCD1, FAS, SREBP2 and HMGCR, and up‐regulated glycogen synthesis proteins, including Akt2 (Ser474) phosphorylation, GLUT2 and GSK‐3β, in the liver of obese mice. However, down‐regulation of FAIM with shRNA promotes obesity. Altogether, our data identified that FAIM mediates the function of PACAP in anti‐inflammation, glucose regulation and lipid metabolism in obese liver.

Hereditary spastic paraplegias refer to a heterogeneous group of neurodegenerative disorders resulting from degeneration of the corticospinal tract. Clinical characterization of patients with hereditary spastic paraplegias represents progressive spasticity, exaggerated reflexes and muscular weakness. Here, to expand on the increasingly broad pools of previously unknown hereditary spastic paraplegia causative genes and subtypes, we performed whole exome sequencing for six affected and two unaffected individuals from two unrelated Chinese families with an autosomal dominant hereditary spastic paraplegia and lacking mutations in known hereditary spastic paraplegia implicated genes. The exome sequencing revealed two stop-gain mutations, c.247_248insGTGAATTC (p.I83Sfs*11) and c.526G>T (p.E176*), in the ubiquitin-associated protein 1 (UBAP1) gene, which co-segregated with the spastic paraplegia. We also identified two UBAP1 frameshift mutations, c.324_325delCA (p.H108Qfs*10) and c.425_426delAG (p.K143Sfs*15), in two unrelated families from an additional 38 Chinese pedigrees with autosomal dominant hereditary spastic paraplegias and lacking mutations in known causative genes. The primary disease presentation was a pure lower limb predominant spastic paraplegia. In vivo downregulation of Ubap1 in zebrafish causes abnormal organismal morphology, inhibited motor neuron outgrowth, decreased mobility, and shorter lifespan. UBAP1 is incorporated into endosomal sorting complexes required for transport complex I and binds ubiquitin to function in endosome sorting. Patient-derived truncated form(s) of UBAP1 cause aberrant endosome clustering, pronounced endosome enlargement, and cytoplasmic accumulation of ubiquitinated proteins in HeLa cells and wild-type mouse cortical neuron cultures. Biochemical and immunocytochemical experiments in cultured cortical neurons derived from transgenic Ubap1flox mice confirmed that disruption of UBAP1 leads to dysregulation of both early endosome processing and ubiquitinated protein sorting. Strikingly, deletion of Ubap1 promotes neurodegeneration, potentially mediated by apoptosis. Our study provides genetic and biochemical evidence that mutations in UBAP1 can cause pure autosomal dominant spastic paraplegia.

Background: Previous studies have suggested that the human Y-chromosome haplogroup Q1a1a-M120, a widespread paternal lineage in East Asian populations, originated in South Siberia. However,...

Objectives Kashgar prefecture is an important transportation and trade hub with a high incidence of tuberculosis. The following study analyzed the composition and differences in Mycobacterium tuberculosis (M.tb) lineage and specific tags to distinguish the lineage of the M.tb in Kashgar prefecture, thus providing a basis for the classification and diagnosis of tuberculosis in this area. Methods Whole-genome sequencing (WGS) of 161 M.tb clinical strains was performed. The phylogenetic tree was constructed using Maximum Likelihood (ML) based on single nucleotide polymorphisms (SNPs) and verified through principal component analysis (PCA). The composition structure of M.tb in different regions was analyzed by combining geographic information. Results M.tb clinical strains were composed of lineage 2 (73/161, 45.34%), lineage 3 (52/161, 32.30%) and lineage 4 (36/161, 22.36%). Moreover, the 3 lineages were subdivided into 11 sublineages, among which lineage 2 included lineage 2.2.2/Asia Ancestral 1 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 2 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 3 (18/73, 24.66%), and lineage 2.2.1-Modern Beijing (39/73, 53.42%). Lineage 3 included lineage 3.2 (14/52, 26.92%) and lineage 3.3 (38/52, 73.08%), while lineage 4 included lineage 4.1 (3/36, 8.33%), lineage 4.2 (2/36, 5.66%), lineage 4.4.2 (1/36, 2.78%), lineage 4.5 (28/36, 77.78%) and lineage 4.8 (2/36, 5.66%), all of which were consistent with the PCA results. One hundred thirty-six markers were proposed for discriminating known circulating strains. Reconstruction of a phylogenetic tree using the 136 SNPs resulted in a tree with the same number of delineated clades. Based on geographical location analysis, the composition of Lineage 2 in Kashgar prefecture (45.34%) was lower compared to other regions in China (54.35%-90.27%), while the composition of Lineage 3 (32.30%) was much higher than in other regions of China (0.92%-2.01%), but lower compared to the bordering Pakistan (70.40%). Conclusion Three lineages were identified in M.tb clinical strains from Kashgar prefecture, with 136 branch-specific SNP. Kashgar borders with countries that have a high incidence of tuberculosis, such as Pakistan and India, which results in a large difference between the M.tb lineage and sublineage distribution in this region and other provinces of China.

Previously, we established an optogenetic model to induce Amyloid-β intracellular oligomerization to model distinct disease etiologies (Limet al. 2020). Here we examine the effect of Wnt signaling on Amyloid in this model. We observe that Wnt activation rescues the detrimental effects of Amyloid expression and oligomerization. We analyze the gene expression changes downstream of Wnt that contribute to this rescue and find changes in aging related genes, protein misfolding, metabolism and inflammation. We propose that Wnt expression reduces inflammation through repression of Toll activating factors and confirm that chronic Toll activation reduces lifespan. We propose that the protective effect observed for Lithium treatment functions at least in part through Wnt activation and inhibition of inflammation.

Background Grain weight and grain shape are important agronomic traits that affect the grain yield potential and grain quality of rice. Both grain weight and grain shape are controlled by multiple genes. The 3,000 Rice Genomes Project (3 K RGP) greatly facilitates the discovery of agriculturally important genetic variants and germplasm resources for grain weight and grain shape. Results Abundant natural variations and distinct phenotic differentiation among the subgroups in grain weight and grain shape were observed in a large population of 2,453 accessions from the 3 K RGP. A total of 21 stable quantitative trait nucleotides (QTNs) for the four traits were consistently identified in at least two of 3-year trials by genome-wide association study (GWAS), including six new QTNs (qTGW3.1, qTGW9, qTGW11, qGL4/qRLW4, qGL10, and qRLW1) for grain weight and grain shape. We further predicted seven candidate genes (Os03g0186600, Os09g0544400, Os11g0163600, Os04g0580700, Os10g0399700, Os10g0400100 and Os01g0171000) for the six new QTNs by high-density association and gene-based haplotype analyses. The favorable haplotypes of the seven candidate genes and five previously cloned genes in elite accessions with high TGW and RLW are also provided. Conclusions Our results deepen the understanding of the genetic basis of grain weight and grain shape in rice and provide valuable information for improving rice grain yield and grain quality through molecular breeding.

The intestinal flora is recognized as a significant contributor to the immune system. In this research, the protective effects of oyster peptides on immune regulation and intestinal microbiota were investigated in mice treated with cyclophosphamide. The results showed that oyster peptides restored the indexes of thymus, spleen and liver, stimulated cytokines secretion and promoted the relative mRNA levels of Th1/Th2 cytokines (IL-2, IFN-γ, IL-4 and IL-10). The mRNA levels of Occludin, Claudin-1, ZO-1, and Mucin-2 were up-regulated, and the NF-κB signaling pathway was also activated after oyster peptides administration. Furthermore, oyster peptides treatment reduced the proportion of Firmicutes/Bacteroidetes, increased the relative abundance of Alistipes, Lactobacillus, Rikenell and the content of short-chain fatty acids, and reversed the composition of intestinal microflora similar to that of normal mice. In conclusion, oyster peptides effectively ameliorated cyclophosphamide-induced intestinal damage and modified gut microbiota structure in mice, and might be utilized as a beneficial ingredient in functional foods for immune regulation.

Proper embryonic development requires directional axes to pattern cells into embryonic structures. In Drosophila, spatially discrete expression of transcription factors determines the anterior to posterior organization of the early embryo, while the Toll and TGFβ signalling pathways determine the early dorsal to ventral pattern. Embryonic MAPK/ERK signaling contributes to both anterior to posterior patterning in the terminal regions and to dorsal to ventral patterning during oogenesis and embryonic stages. Here we describe a novel loss of function mutation in the Raf kinase gene, which leads to loss of ventral cell fates as seen through the loss of the ventral furrow, the absence of Dorsal/NFκB nuclear localization, the absence of mesoderm determinants Twist and Snail, and the expansion of TGFβ. Gene expression analysis showed cells adopting ectodermal fates much like loss of Toll signaling. Our results combine novel mutants, live imaging, optogenetics and transcriptomics to establish a novel role for Raf, that appears to be independent of the MAPK cascade, in embryonic patterning.

MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs that regulate gene expression at the translation level in cell growth, proliferation and differentiation. In addition, some types of miRNAs have been proven to be key modulators of both CNS development and plasticity, such as let-7, miR-9 and miR-124. In this research, we found miR-8b acts as an important regulator involved in brain and eyespot regeneration in Dugesia japonica. miR-8b was highly conserved among species and was abundantly expressed in central nervous system. Here, we detected the expression dynamics of miR-8b by qPCR during the head regeneration of D. japonica. Knockdown miR-8b by anti-MIRs method caused severe defects of eyes and CNS. Our study revealed the evolutionary conserved role of miR-8b in the planarian regeneration process, and further provided more research ideas and available information for planarian miRNAs., Summary: Most miRNAs in planarians are homologous to humans and other mammals, and may also play a similar regulatory role. Knockdown miR-8b planarian miR-8b induces brain and eyespot defects during head regeneration.

The nigrostriatal dopaminergic (DA) system, which includes DA neurons in the ventral and dorsal tiers of the substantia nigra pars compacta (vSNc, dSNc) and DA terminals in the dorsal striatum, is critically implicated in motor control. Accumulating studies demonstrate that both the nigrostriatal DA system and motor function are impaired in aged subjects. However, it is unknown whether dSNc and vSNc DA neurons and striatal DA terminals age in similar patterns, and whether these changes parallel motor deficits. To address this, we performed ex vivo patch-clamp recordings in dSNc and vSNc DA neurons, measured striatal dopamine release, and analyzed motor behaviors in rodents. Spontaneous firing in dSNc and vSNc DA neurons and depolarization-evoked firing in dSNc DA neurons showed inverse V-shaped changes with age. But depolarization-evoked firing in vSNc DA neurons increased with age. In the dorsal striatum, dopamine release declined with age. In locomotor tests, 12-month-old rodents showed hyperactive exploration, relative to 6- and 24-month-old rodents. Additionally, aged rodents showed significant deficits in coordination. Elevating dopamine levels with a dopamine transporter inhibitor improved both locomotion and coordination. Therefore, key components in the nigrostriatal DA system exhibit distinct aging patterns and may contribute to age-related alterations in locomotion and coordination.

Breast cancer is the most common type of cancer diagnosed among women, and basal-like breast carcinoma (BLBC) has been associated with a more aggressive histology, poorer prognosis, and non-responsiveness to hormone therapy. In the present study, the role and molecular mechanism of circular (circ)_NOTCH3 in the development and progression for BLBC was identified. circ_RNAs array was used to screen the ectopic expression of hsa_circ_0109177 (circ_NOTCH3) in BLBC. RT-qPCR was conducted to evaluate the circ_NOTCH3 expression in BLBC tissues and paired normal tissues, as well as related cell lines. Cell function changes were analyzed following circ_NOTCH3 or micro (mi)RNA overexpression or co-expression. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the binding sites between circ_NOTCH3 and miRNAs. Gene expression changes were assessed using western blotting. circ_NOTCH3 had a significantly higher expression in BLBC tissues and cell lines. The upregulation of circ_NOTCH3 promoted the proliferation, migration, invasion and inhibited the apoptosis for BLBC cells. The opposite results were observed following miR-205-5p overexpression. However, the co-expression of circ_NOTCH3 and miR-205-5p resulted in those restoration. circ_NOTCH3 is capable of binding to miR-205-5p, and upregulating its target gene KLF12, which can be downregulated by miR-205-5p overexpression and restored by the co-expression of circ_NOTCH3 and miR205-5p. circ_NOTCH3, being an protooncogene and a powerful biomarker, can function as a sponge, compete with miR-205-5p, modulate KLF12 expression, and promote the development and progression of BLBC.

A large number of colorectal cancers have a genetic background in China. However, due to insufficient awareness, the diagnostic rate remains low and merely 5-6% of colorectal cancer patients are diagnosed with hereditary colorectal cancer. Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease caused by mutations in the adenomatous polyposis coli (APC) gene. Different mutation sites in APC are associated with the severity of FAP, risks of carcinogenesis, and extraintestinal manifestations. We used next-generation sequencing (NGS) and capture techniques to screen suspected mutation points in the proband in this pedigree. Using modified Sanger sequencing, we identified members of the family who were carriers of this variant and whether this segregated well with disease occurrence. FAP family members had multiple adenomatous polyps in their gastrointestinal tracts, some of which developed into cancer with age. Two subjects presented a rare common bile duct polyp phenotype. No extraintestinal manifestations were observed. A heterozygous frameshift mutation in APC exon 16 (NM_000038.6) was observed in the proband and in other patients: c.3260_3261del (p.Leu1087GlnQfs ∗ 31) (rs587782305); the variant call format was CCT/C. Due to the deletion of two bases, a stop codon appeared after 31 amino acids, and the protein was truncated prematurely, which affected the conformation of the protein. Pedigree genetic linkage analysis showed that the clinical phenotype cosegregated with the APC mutation p.L1087fs. This mutation may be the pathogenic in this FAP family and responsible for this rare common bile duct polyp.

Mongolian populations are widely distributed geographically, showing abundant ethnic diversity with geographic and tribal differences. To infer the genetic substructure, admixture and ancient genetic sources of Mongolians together with Kazakhs We genotyped more than 690,000 genome-wide SNPs from 33 Mongolian and Chinese Kazakh individuals and compared these with both ancient and present-day Eurasian populations using Principal Component Analysis (PCA), ADMIXTURE, Refine-IBD, f statistics, qpWave and qpAdm. We found genetic substructures within Mongolians corresponding to Ölöd, Chahar, and Inner Mongolian clusters, which was consistent with tribe classifications. Mongolian and Kazakh groups derived about 6–40% of West Eurasian related ancestry, most likely from Bronze Age Steppe populations. The East Asian related ancestry in Mongolian and Kazakh groups was well represented by the Neolithic DevilsCave related nomadic lineage, comprising 42–64% of studied groups. We also detected 10–51% of Han Chinese related ancestry in Mongolian and Kazakh groups, especially in Inner Mongolians. The average admixture times for Inner Mongolian, Mongolian_Chahar, Mongolian_Ölöd and Chinese Kazakh were about 1381, 626, 635 and 632 years ago, respectively, with Han and French as the sources. The DevilsCave related ancestry was once widespread westwards covering a wide geographical range from Far East Russia to the Mongolia Plateau. The formation of present-day Mongolic and Turkic-speaking populations has also received genetic influence from agricultural expansion.

The present study aimed to investigate the potential of simple sugars for use as protection agents in the control of tomato bacterial wilt caused by Ralstonia pseudosolanacearum. Based on the sugar assimilation patterns of the pathogen, four unassimilable sugars (L-arabinose, maltose, D-raffinose, and D-ribose) were selected from 10 representative sugars present in tomato root exudates. These sugars were evaluated for their effects on bacterial wilt using a tomato seedling bioassay. The application of 0.25% L-arabinose significantly reduced disease severity and was, thus, selected as a candidate for further evaluations in a pot experiment under glasshouse conditions. The results obtained showed that the disease suppressive effects of L-arabinose slightly increased at higher concentrations; drench treatments at 0.1, 0.25, and 0.5% reduced disease severity by ca. 48, 70, and 87%, respectively. The drench treatment with 0.5% L-arabinose significantly reduced the pathogen population in the rhizosphere and stem tissues of tomato plants without any antibacterial activity. Real-time reverse-transcription PCR revealed that the expression of salicylic acid-dependent and ethylene-dependent defense genes was significantly enhanced in the stem tissues of L-arabinose-treated tomato plants following the pathogen inoculation. These results suggest that soil drenching with L-arabinose effectively suppresses tomato bacterial wilt by preventing pathogen proliferation in the rhizosphere and stem tissues of tomato plants. This is the first study to report the potential of L-arabinose as a safe, eco-friendly, and cost-effective plant protection agent for the control of tomato bacterial wilt.

Background Acting as a cellular cleaner by packaging and transporting defective proteins and organelles to lysosomes for breakdown, autophagic process is involved in the regulation of cell remodeling after cell damage or cell death in both vertebrate and invertebrate. In human, limitations on the regenerative capacity of specific tissues and organs make it difficult to recover from diseases. Comprehensive understanding on its mechanism within invertebrate have strong potential provide helpful information for challenging these diseases. Method In this study, recent findings on the autophagy function in three invertebrates including planarian, hydra and leech with remarkable regenerative ability were summarized. Furthermore, molecular phylogenetic analyses of DjATGs and HvATGs were performed on these three invertebrates compared to that of Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens. Results In comparison with Scerevisiae, C elegans, D melanogaster, M musculus and human, our analysis exhibits the following characteristics of autophagy and its function in regeneration within invertebrate. Phylogenetical analysis of ATGs revealed that most autophagy-related genes (ATGs) were highly similar to their homologs in other species, which indicates that autophagy is a highly conservative biological function in both vertebrate and invertebrate. Structurally, almost all the core amino acids necessary for the function of ATG8 in mammal were observed in invertebrate HvATG8s and DjATG8s. For instance, ubiquitin-like domain as a signature structure in each ATG8, was observed in all ATG8s in three invertebrates. Basically, autophagy plays a key role in the regulation of regeneration in planarian. DjATG8-2 and DjATG8-3 associated with mTOR signaling pathway are sophisticated in the invertebrate tissue/organ regeneration. Furthermore, autophagy is involved in the pathway of neutralization of toxic molecules input from blood digestion in the leech. Conclusions The recent investigations on autophagy in invertebrate including planarian, hydra and leech suggest that autophagy is evolutionally conserved from yeast to mammals. The fundamental role of its biological function in the invertebrate contributing to the regeneration and maintenance of cellular homeostasis in these three organisms could make tremendous information to confront life threatening diseases in human including cancers and cardiac disorders.

Objectives The origin and differentiation of Austronesian populations and their languages have long fascinated linguists, archeologists, and geneticists. However, the founding process of Austronesians and when they separated from their close relatives, such as the Daic and Austro-Asiatic populations in the mainland of Asia, remain unclear. In this study, we explored the paternal origin of Malays in Southeast Asia and the early differentiation of Austronesians. Materials and methods We generated whole Y-chromosome sequences of 50 Malays and co-analyzed 200 sequences from other Austronesians and related populations. We generated a revised phylogenetic tree with time estimation. Results We identified six founding paternal lineages among the studied Malays samples. These founding lineages showed a surprisingly coincident expansion age at 5000 to 6000 years ago. We also found numerous mostly close related samples of the founding lineages of Malays among populations from Mainland of Asia. Conclusion Our analyses provided a refined phylogenetic resolution for the dominant paternal lineages of Austronesians found by previous studies. We suggested that the co-expansion of numerous founding paternal lineages corresponds to the initial differentiation of the most recent common ancestor of modern Austronesians. The splitting time and divergence pattern in perspective of paternal Y-chromosome evidence are highly consistent with the previous theories of ethnologists, linguists, and archeologists.

Objectives Haplogroup C2a-M48 is the predominant paternal lineage of Tungusic-speaking populations, one of the largest population groups in Siberia. Up until now, the origins and dispersal of Tungusic-speaking populations have remained unclear. In this study, the demographic history of Tungusic-speaking populations was explored using the phylogenetic analysis of haplogroup C2a-M86, the major subbranch of C2a-M48. Materials and methods In total, 18 newly generated Y chromosome sequences from C2a-M48 males and 20 previously available Y-chromosome sequences from this haplogroup were analyzed. A highly revised phylogenetic tree of haplogroup C2a-M86 with age estimates was reconstructed. Frequencies of this lineage in the literature were collected and a comprehensive analysis of this lineage in 13 022 individuals from 245 populations in Eurasia was performed. Results The distribution map of C2a-M48 indicated the most probable area of origin and diffusion route of this paternal lineage in North Eurasia. Most C2a-M86 samples from Tungusic-speaking populations belonged to the sublineage C2a-F5484, which emerged about 3300 years ago. We identified six unique sublineages corresponding to the Manchu, Evenks, Evens, Oroqen, and Daurpopulations; these sublineages diverged gradually over the past 1900 years. Notably, we observed a clear north-south dichotomous structure for sublineages derived from C2a-F5484, consistent with the internal north-south divergence of Tungusic languages and ethnic groups. Conclusions We identified the important founding paternal haplogroup, C2a-F5484, for Tungusic-speaking populations as well as numerous unique subgroups of this haplogroup. We propose that the timeframe for the divergence of C2a-F5484 corresponds with the early differentiation of ancestral Tungusic-speaking populations.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

As a two-dimensional (2D) ordered porous organic framework (POF), PAF-6 is demonstrated to have an extraordinarily high fluorescence quenching ability to dye-labeled single-stranded DNA (ssDNA). Based on its different affinities to ssDNA and double-stranded DNA (dsDNA), and to ssDNAs with different lengths, PAF-6 is firstly utilized as a simple, cost-efficient, sensitive and selective sensing platform for sequence-specific detection of DNA and activity analysis of exonuclease I (Exo I). In these two systems, the sensing approach is accomplished by simply mixing the dye-labeled ssDNA probe with the targets and PAF-6. The targets of DNA and Exo I are specifically and sensitively detected with detection limits of 0.6 nM and 0.03 U mL−1 (S/N = 3), respectively, by using PAF-6 as a fluorescence quencher of the dye-labeled ssDNA probe. The results of this study suggest that PAF-6 can be developed as an excellent platform for the detection of nucleic acid and nuclease activity. In addition, PAF-6 exhibits a remarkable ability to protect ssDNA probe from enzymatic digestion, which may greatly extend the applications of the proposed ssDNA probe/PAF-6 sensing system to bioanalysis and biomedicine.

To observe the effects of electroacupuncture (EA) of three different frequencies (2 Hz, 80 Hz and 2 Hz/80 Hz) on the free radicals in hippocampus of vascular dementia (VD) model mice. A total of 100 Kunming mice were randomly divided into a sham operation group, a model group, a 2 Hz EA group, an 80 Hz EA group and a 2 Hz/80 Hz EA group, with 20 mice in each group. The ischemia-reperfusion VD model was established by repeated blockade of bilateral common carotid arteries. Mice in EA groups began EA treatment on the 4th day after the operation. Baihui (GV 20), Dazhui (GV 14), Geshu (BL 17) and Zusanli (ST 36) were punctured and then connected to EA instrument, with different waves of 2 Hz, 80 Hz or 2 Hz/80 Hz (10 min/time) applied accordingly, once a day. During the jumping stand experiment, the learning performance, memory performance and hippocampal calcitonin gene-related peptide (CGRP), nitric oxide synthase (NOS), malondialdehyde (MDA), changes in superoxide dismutase (SOD) and true choline esterase (TChE) were observed. In hippocampus, the CGRP level was determined by radioimmunoassay; the MDA level was determined by thiobarbituric acid colorimetric method; the activities of NOS and TChE were determined by spectrophotometry; the activity of SOD was determined by xanthine oxidase method. Compared with the sham operation group, the performances of learning and memory decreased significantly in the model group (P

Background: miR-24-3p is a microRNA (miRNA) that is involved in the differentiation of various types of cancers and has been shown to act as an oncogene or tumor suppressor in certain cancers. However, the underlying mechanism of the miR-24-3p/TEL2 pathway has not been elucidated yet. Methods: The expression of miR-24-3p mRNA in NP69 cells and five NPC cell lines was detected. miR-24-3p mimics were transfected into S26 and 6-10B cells to explore the effect of miR-24-3p on the TEL2 mRNA and protein levels in NPC by Western blotting. In addition, tissue was collected from 116 patients with NPC, and total RNA was extracted for qRT-PCR to determine the expression of levels TEL2 and miR-24-3p. Furthermore, Transwell assays were conducted to study the effect of cancer cell migration and invasion. Results: In this study, we found that ectopic expression of miR-24-3p decreased the mRNA and protein levels of TEL2 in NPC cells, while knockdown of miR-24-3p increased the mRNA and protein levels of TEL2. Additionally, there was a negative correlation between miR-24-3p and TEL2 in NPC tissues. Mechanistically, we showed that miR-24-3p inhibits TEL2 expression via direct binding to the 3' untranslated region (3' UTR) of TEL2. Conclusions: Collectively, our results suggest that the miR-24-3p/TEL2 pathway may be a new target for treating patients with NPC.

Background Hereditary spastic paraplegias (HSP) is a heterogeneous group of rare neurodegenerative disorders affecting the corticospinal tracts. To date, more than 78 HSP loci have been mapped to cause HSP. However, both the clinical and mutational spectrum of Chinese patients with HSP remained unclear. In this study, we aim to perform a comprehensive analysis of clinical phenotypes and genetic distributions in a large cohort of Chinese HSP patients, and to elucidate the primary pathogenesis in this population. Methods We firstly performed next-generation sequencing targeting 149 genes correlated with HSP in 99 index cases of our cohort. Multiplex ligation-dependent probe amplification testing was further carried out among those patients without known disease-causing gene mutations. We simultaneously performed a retrospective study on the reported patients exhibiting HSP in other Chinese cohorts. All clinical and molecular characterization from above two groups of Chinese HSP patients were analyzed and summarized. Eventually, we further validated the cellular changes in fibroblasts of two major spastic paraplegia (SPG) patients (SPG4 and SPG11) in vitro. Results Most patients of ADHSP (94%) are pure forms, whereas most patients of ARHSP (78%) tend to be complicated forms. In ADHSP, we found that SPG4 (79%) was the most prevalent, followed by SPG3A (11%), SPG6 (4%) and SPG33 (2%). Subtle mutations were the common genetic cause for SPG4 patients and most of them located in AAA cassette domain of spastin protein. In ARHSP, the most common subtype was SPG11 (53%), followed by SPG5 (32%), SPG35 (6%) and SPG46 (3%). Moreover, haplotype analysis showed a unique haplotype was shared in 14 families carrying c.334C > T (p.R112*) mutation in CYP7B1 gene, suggesting the founder effect. Functionally, we observed significantly different patterns of mitochondrial dynamics and network, decreased mitochondrial membrane potential (Δψm), increased reactive oxygen species and reduced ATP content in SPG4 fibroblasts. Moreover, we also found the enlargement of LAMP1-positive organelles and abnormal accumulation of autolysosomes in SPG11 fibroblasts. Conclusions Our study present a comprehensive clinical spectrum and genetic landscape for HSP in China. We have also provided additional evidences for mitochondrial and autolysosomal-mediated pathways in the pathogenesis of HSP. Electronic supplementary material The online version of this article (10.1186/s13024-018-0269-1) contains supplementary material, which is available to authorized users.

Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-β1) and p53, and corresponding high-mobility group box 1 (HMGB1) signaling and T helper cell differentiation were thought to be associated with matrine’s mechanism. Expression of predicted serum targets were verified in a 1,2-dimethylhydrazine dihydrochloride-induced CRC model rats that were treated with matrine (ip) for 18 weeks. Data show that matrine suppressed CRC growth and decreased previously elevated expression of IL-6, TNF-α, p53, and HMGB1. Matrine may have had a therapeutic effect on CRC via inhibition of HMGB1 signaling, and this occurred through downregulation of IL-6, TNF-α, and HMGB1.

Primary familial brain calcification (PFBC) is a neuropsychiatric disorder characterized by bilateral cerebral calcification with diverse neurologic or psychiatric symptoms. Recently, XPR1 variation has accounted for PFBC as another new causative gene. However, little is known about the distribution and basic function of XPR1 and its interaction with the other three pathogenic genes for PFBC (SLC20A2, PDGFRB and PDGFB). The aim of this study was to further clarify the role of XPR1 in PFBC brain pathology. As a result, gene expression profiles showed that XPR1 mRNA was widely expressed throughout the mouse brain. Cerebellum and striatum, most commonly affected in PFBC, contained a higher level of XPR1 protein than other brain regions. Additionally, XPR1 deficiency seriously affected Pi efflux and XPR1 mutations seemed to have an effect through haploinsufficiency mechanism. The immunoprecipitation and immunohistochemical studies demonstrated that XPR1 could interact with PDGFRB and might form a complex on the cell membrane. These results suggested that XPR1 played a fundamental role in the maintenance of cellular phosphate balance in the brain. This provided us with a novel perspective on understanding the pathophysiology of PFBC. The expression networks and interaction with the known pathogenic genes could shed new light on additional candidate genes for PFBC.

Marek’s disease virus type 1 (MDV-1) is a representative oncogenic Alpha herpesvirus that causes an immunosuppressive and neoplastic lymphoproliferative avian disease, namely Marek’s disease (MD). The rapid-onset T-cell lymphoma in chickens induced by MDV-1 has been historically regarded as an ideal natural model for herpesvirus-related cancer research. As a viral analog of cellular miR-155, the MDV-1-encoded miR-M4-5p has been shown to be crucial for the virally-induced MD tumorigenesis. Our previous studies demonstrated that miR-M4-5p induces an over-expression of oncogene c-Myc by targeting LTBP1 and suppressing the TGF-β signaling pathway during MDV-1 infection. We have now further identified the chicken heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) as a new cellular biological target for miR-M4-5p. Suppression of hnRNPAB expression mediated by miR-M4-5p promotes the proliferation, but not the apoptosis, of both primary chicken embryo fibroblasts (CEFs) and transformed chicken fibroblast DF-1 cell line. HnRNPAB is a member of the hnRNP family of proteins that play important roles in normal biological processes as well as cancer development. Our data suggests that the recognition and down-regulation of hnRNPAB by miR-M4-5p may be one of the important strategies for MDV-1 to trigger the development of MD lymphomas.

Ammonia oxidation is the rate-limiting and central step in global biogeochemistry cycle of nitrogen. A bibliometric analysis based on 4314 articles extracted from Science Citation Index Expanded database was carried out to provide insights into publication performances and research trends of ammonia oxidation in the period 1991-2014. These articles were originated from a wide range of 602 journals and 95 Web of Science Categories, among which Applied and Environmental Microbiology and Environmental Sciences took the leading position, respectively. Furthermore, co-citation analysis conducted with help of CiteSpace software clearly illustrated that ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA), and anaerobic ammonia oxidation (anammox) were three dominant research themes. A total of 15 landmark works identified with the highest co-citation frequencies at every 8 years were extracted, which demonstrated that the establishments of culture-independent molecular biotechnologies as well as the discoveries of anammox and AOA played the most significant roles in promoting the evolution and development of ammonia oxidation research. Finally, word cluster analysis further suggested that microbial abundance and community of AOA and AOB was the most prominent hotspot, with soil and high-throughput sequencing as the most promising ecosystem and molecular biotechnology. In addition, application of anammox in nitrogen removal from wastewater has become another attractive research hotspot. This study provides a basis for better understanding the situations and prospective directions of the research field of ammonia oxidation.

14-3-3 proteins are a family of highly conserved acidic proteins that regulate cellular processes. They act as a kind of important signaling molecules taking part in many crucial decisions throughout the development process. We have isolated and characterized two members of the 14-3-3 family, namely, Dj14-3-3 α and Dj14-3-3 ζ in the planarian Dugesia japonica. The Dj14-3-3 α and ζ genes encode polypeptides of 260 and 255 amino acids respectively. We have proved that the Dj14-3-3 α and ζ genes were especially expressed in the pharynx in adult and regenerating planarians by in situ hybridization and they were not involved in regeneration process. Besides, Dj14-3-3 α and ζ genes can compensate each other in planarians by RNA interference. The Dj14-3-3 α and ζ were significantly up-regulated expression when planarians were stimulated with the pathogen-associated molecular patterns including lipopolysaccharide (LPS), peptidoglycan (PGN), β-Glu and Poly (I:C), indicating that the Dj14-3-3 α and ζ may be involved in the immune responses.

Temperature is an important factor governing the community traits of N2O-emission related functional guilds (mainly autotrophic ammonia oxidizers and heterotrophic denitrifiers) and their activities. However, there have been few attempts to explore the broad response patterns of these guilds to temperature changes across arable soils. For this, a temperature-controlled (15, 25 and 35 °C) microcosm experiment was conducted using three arable soils (Fujian, Gansu, and Jiangsu) in China under two different fertilizations (no fertilization control (CK) and inorganic fertilization (NPK)). In conjunction with the measurement of N2O emission, the community structure and abundance of ammonia oxidizing archaea (AOA) and bacteria (AOB), as well as nirS- and nirK-denitrifiers were assessed using T-RFLP and quantitative PCR, respectively. The analysis of community traits indicated a consistent response pattern of AOAs to temperature in terms of guild abundance, and a consistent effect of inorganic fertilization on the abundance of AOBs, but soil-dependent response patterns to fertilization and temperature were found for nirS- and nirK-denitrifiers in terms of abundance and community structure. The correlation analysis suggested that AOAs possibly assumed a role in N2O emission in all the tested soils, and nirS-denitrifiers probably participated in N2O emission in both the Fujian and Gansu soil, while a considerable amount of N2O emission in the Jiangsu soil might have been derived from heterotrophic nitrification.

Recently, certain studies have demonstrated in vitro that prostaglandin E2 (PGE2) promotes human cluster of differentiation (CD)34+ cell homing. However, the sub‑type receptors activated by PGE2 are unknown, as the PGE2 receptor EP1-4 subtypes (EP1-4) are expressed on the membrane of human CD34+ cells. Based on the above, the present study aimed to screen the receptor subtype activity by PGE2 to promote human CD34+ cell homing. It was observed that human CD34+ cells expressed the four PGE2 sub‑receptors, particularly EP2 and 4. PGE2 increased EP2 and 4 mRNA expression significantly, while EP1 and 3 mRNA exhibited no significant alteration. PGE2, EP2 agonist (EP2A), and EP4A upregulated C‑X‑C chemokine receptor 4 mRNA and protein expression in human CD34+ cells, and promoted stromal cell‑derived factor 1α (SDF‑1α) expression in bone marrow mesenchymal stem cells (BMMSCs). These phenomena were inhibited by the associated receptor antagonists. PGE2, EP2A, and EP4A facilitated human CD34+ cell migration towards SDF‑1α and BMMSCs. The results of the present study suggested that PGE2 promoted human CD34+ cell homing through EP2 and 4 receptors in vitro.

Idiopathic pulmonary fibrosis is known as a life-threatening disease with high mortality and limited therapeutic strategies. In addition, the molecular mechanism by which pulmonary fibrosis developed is not fully understood. Asiatic acid (AA) is a triterpenoid, isolated from Centella asiatica, exhibiting efficient anti-inflammatory and anti-oxidative activities. In our study, we attempted to explore the effect of Asiatic acid on bleomycin (BLM)-induced pulmonary fibrosis in mice. The findings indicated that pre-treatment with Asiatic acid inhibited BLM-induced lung injury and fibrosis progression in mice. Further, Asiatic acid down-regulates inflammatory cells infiltration in bronchoalveolar lavage fluid (BALF) and pro-inflammatory cytokines expression in lung tissue specimens induced by BLM. Also, Asiatic acid apparently suppressed transforming growth factor-beta 1 (TGF-β1) expression in tissues of lung, accompanied with Collagen I, Collagen III, α-SMA and matrix metalloproteinase (TIMP)-1 decreasing, as well as Smads and ERK1/2 inactivation. Of note, Asiatic acid reduces NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome. The findings indicated that Asiatic acid might be an effective candidate for pulmonary fibrosis and inflammation treatment.

Vatica guangxiensis S.L. Mo is an evergreen large tree of Dipterocarpaceae. Herein, we assembled the complete chloroplast genome of Vatica guangxiensis by next-generation sequencing technologies. The complete chloroplast genome sequence of Vatica guangxiensis is 151,010 base pairs (bp) in length, including a pair of inverted repeat regions (IRs, 23,827 bp), one large single-copy region (LSC, 83,353 bp), one small single-copy region (SSC, 20,003 bp). Besides, the complete chloroplast genome contains 123 genes in total, including 83 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. Phylogenetic analysis showed that Vatica guangxiensis has the closest relationship with Vatica mangachapoi. Our study lay a foundation for further research of Vatica mangachapoi.

Paphiopedilum emersonii is an endemic terrestrial orchid in China. In this study, the chloroplast genome of P. emersonii was determined from BGISEQ-500 sequencing data. The total chloroplast genome was 162,590 bp in length, consisting of a large single-copy region (LSC, 87,852 bp), a small single-copy region (SSC, 870 bp), and two inverted repeat regions (IRA and IRB, 36,934 bp, each). The complete chloroplast genome contains 131 genes, including 81 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. In addition, the phylogenetic analysis indicates that P. emersonii was sister to Paphiopedilum micranthum. The chloroplast genome will contribute to the research and conservation of P. emersonii.

Liquidambar formosana (Hamamelidaceae) is a tertiary relic species widely distributed in subtropical areas, and is a common endemic broad-leaved tree species in south China. Here, we report and describe for the first time the complete chloroplast genome of L. formosana based on Illumina double-ended sequencing data. The complete plastid genome was 160,425 bp, which contained inverted repeats (IR) of 26,266 bp separated by a large single-copy (LSC) and a small single-copy (SSC) of 88,971 bp and 18,922 bp, respectively. The cpDNA contains 132 genes, comprising 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the plastome is 37.9%. The phylogenetic analysis of 18 selected chloroplast genomes demonstrated that L. formosana was close to the species Sinowilsonia henryi.

The aim of the present study was to identify a strain of endophytic Bacillus species that control tomato bacterial wilt by foliar spray application. Fifty heat-tolerant endophytic bacteria were isolated from the surface-sterilized foliar tissues of symptomless tomato plants that had been pre-inoculated with the pathogen Ralstonia pseudosolanacearum. In the primary screening, we assessed the suppressive effects of a shoot-dipping treatment with bacterial strains against bacterial wilt on tomato seedlings grown on peat pellets. Bacillus sp. strains G1S3 and G4L1 significantly suppressed the incidence of tomato bacterial wilt. In subsequent pot experiments, the biocontrol efficacy of foliar spray application was examined under glasshouse conditions. G4L1 displayed consistent and significant disease suppression, and, thus, was selected as a biocontrol candidate. Moreover, the pathogen population in the stem of G4L1-treated plants was markedly smaller than that in control plants. A quantitative real-time PCR analysis revealed that the foliar spraying of tomato plants with G4L1 up-regulated the expression of PR-1a and LoxD in stem and GluB in roots upon the pathogen inoculation, implying that the induction of salicylic acid-, jasmonic acid-, and ethylene-dependent defenses was involved in the protective effects of this strain. In the re-isolation experiment, G4L1 efficiently colonized foliar tissues for at least 4‍ ‍weeks after spray application. Collectively, the present results indicate that G4L1 is a promising biocontrol agent for tomato bacterial wilt. Furthermore, to the best of our knowledge, this is the first study to report the biocontrol of bacterial wilt by the foliar spraying with an endophytic Bacillus species.

Visfatin acts as a significant regulator of inflammatory cytokines. However, the immunological response and therapeutic effects of visfatin under bacterial stress in murine lung tissue are still not clear. To investigate the role of visfatin on lipopolysaccharide (LPS)-induced acute lung injury (ALI), thirty Kunming mice were divided into Saline, LPS, and LPS + visfatin groups. After routine blood examination, the effects of visfatin on inflammatory cytokines, lung tissue structure, and expression of inflammatory mediators were explored through hematoxylin-eosin (HE), Masson and immunohistochemical staining, quantitative polymerase chain reaction (Q-PCR), and Western blotting. Compared with the Saline group, neutrophil percentage, peripheral blood neutrophil count, and the ratio of lymphocyte count (NLR) were upregulated in LPS group. Moreover, Masson staining showed alterations in lung tissue structure; the mRNA level of different cytokines (IL-6, IL-1β, TNF-α, IL-10, TLR4, IFN-γ) was upregulated; and the protein expression of interleukin (IL)-6, myeloperoxidase (MPO), and transforming growth factor-β1 (TGF-β) was significantly (p 0.05) different in LPS group. Compared with LPS group, neutrophil percentage significantly decreased (p 0.01), the numbers of lymphocytes significantly (p 0.05) increased, NLR decreased, Masson staining of the lung was extremely different (p 0.01), the structure of the lung was slightly damaged, and the myeloperoxidase values of lung showed no differences in LPS + visfatin. Hence, visfatin inhibits the lung inflammation induced by ALI. During the ALI, visfatin acts by decreasing NLR, downregulated the expression of MPO, enhanced antioxidant capacity, and regulated the inflammatory factors IL-1β, IL-6, IL-10, and TNF-α to reduce the lung injury.

Introduction This randomized, double-blind trial aimed to test effect of a Chinese herbal medicine, Qinggongshoutao (QGST) pill, on the cognition and progression of amnestic mild cognitive impairment (aMCI). Methods Patients with aMCI were randomly assigned to receive QGST, Ginkgo biloba extract, or placebo for 52 weeks. The primary outcome measures were progression to possible or probable Alzheimer's disease (AD) and change in Alzheimer's Disease Assessment Scale–cognitive subscale scores; secondary outcome measures included assessments for cognition and function. Results Total 350 patients were enrolled, possible or probable AD developed in 10. There were significant differences in the probability of progression to AD in the QGST group (1.15%) compared with placebo group (10%). There was significant difference in Alzheimer's Disease Assessment Scale–cognitive subscale scores in favor of QGST over the placebo group. Secondary outcome measure (Mini-Mental State Examination) also showed benefit in QGST at end point. Discussion In patients with aMCI, QGST showed lower AD progression rate than placebo at 8.85%, and may have benefit on global cognition.

Aristolochia kechangensis Y. D. Peng & L.Y. Yu, a new species from northwestern Guangxi, China, is described and illustrated. Based on morphology, the species is referred to Aristolochia subg. Isotrema. The species is similar to A. kwangsiensis and is found in karstic limestone habitats, with ovate‐rounded to heart‐shaped blades and 1–4‐flowered racemose inflorescences, but differs from the latter by a heart‐shaped (versus rounded) blade base, yellow‐green limbs with densely brown nervules (versus red to purple limbs with tuberculate ornamentation), and slender fruit with a diameter of ca 1.5 cm (versus robust fruit with a diameter of ca 2 cm). The leaf epidermis of the new species is characterized by tuberculate protuberances. We present a detailed description, with line drawings, distribution map and color plate, and compare it to related species based on morphological characters. An updated key to Aristolochia distributed in Guangxi region is provided.

Alzheimer's disease (AD) is characterized by β‐amyloid (Aβ) deposition and Tau phosphorylation, in which its pathogenesis has not been cleared so far. The metabolism of Aβ and Tau is critically affected by the autophagy. Abnormal autophagy is thought to be involved in the pathogenesis of AD, regulating autophagy may become a new strategy for AD treatment. In the early stage of AD, the presence of Aβ and Tau can induce autophagy to promote their clearance by means of mTOR‐dependent and independent manners. As AD progress, the autophagy goes aberrant. As a result, Aβ and Tau generate continually, which aggravates both autophagy dysfunction and AD. Besides, several related genes and proteins of AD can also adapt autophagy to make an effect on the AD development. There seems to be a bi‐directional relationship between AD pathology and autophagy. At present, this article reviews this relationship from these aspects: (a) the signaling pathways of regulating autophagy; (b) the relationships between the autophagy and the processing of Aβ; (c) Aβ and Tau cause autophagy dysfunction; (d) normal autophagy promotes the clearance of Aβ and Tau; (e) the relationships between the autophagy and both genes and proteins related to AD: TFEB, miRNAs, Beclin‐1, Presenilin, and Nrf2; and (f) the small molecules regulating autophagy on AD therapy. All of the above may help to further elucidate the pathogenesis of AD and provide a theoretical basis for clinical treatment of AD.

Four causative genes, including solute carrier family 20 member 2 (SLC20A2), platelet-derived growth factor receptor b (PDGFRB), platelet-derived growth factor b (PDGFB)and xenotropic and polytropic retrovirus receptor 1 (XPR1), have been identified to cause primary familial brain calcification (PFBC). However, PDGFRB mutations seem to be quite rare and no PDGFRB mutations have been reported in Chinese PFBC patients. A total of 146 PFBC patients including 12 families and 134 sporadic patients were recruited in this study. All of them were previously tested negative for the SLC20A2. Mutational analyses of the entire exons and exon-intron boundaries of PDGFRB were carried out by direct gene sequencing. In silico analyses of the identified variants were conducted using Mutation Taster, PolyPhen-2 and Sorts Intolerant From Tolerant. Two heterozygous variants, c.3G>A and c.2209G>A, of the PDGFRB gene were revealed in two PFBC families, respectively. These two variants were not observed in 200 healthy controls. The variant c.3G>A was located in exon 2 and affected the initiation codon of the PDGFRB gene. The variant c.2209G>A resulted in amino-acid substitutions of aspartic acid to asparagine at position 737. Both of these two variants co-segregated with the disease phenotype (variant carriers in Family 1: I1, II2 and II3; variant carriers in Family 2: I2 and II8), suggesting a pathogenic impact of these variants. The prevalence of PDGFRB mutations in Chinese PFBC patients seems to be quite low, indicating that PDGFRB is not a major causative gene of PFBC in Chinese population.