Mazusjiangshiense (Mazaceae), a new species from China: evidence from morphological and molecular analyses.

Utilising both morphological and molecular analyses, this study unveils Mazusjiangshiensesp. nov., a novel addition to the Mazaceae family, discovered in Shaowu County, Fujian Province, China. The comprehensive description and illustrations provided here are a result of a meticulous exploration of its morphological features. While bearing a resemblance to M.gracilis, this new-found species is distinguished by three distinct characteristics: its stems are delicately soft, its leaves possess a membranous quality and the ovary is notably villous at the apex. Integration of molecular evidence, derived from the nuclear ribosomal DNA (nrITS) and three plastid DNA sequences (rps16, rbcL and trnL-trnF), unequivocally supports the classification of M.jiangshiense as a distinct species. Notably, the molecular analysis positions it as a sister species to M.spicatus, underscoring the phylogenetic relationships within the genus Mazus. Our research not only introduces M.jiangshiense as a novel taxonomic entity, but also provides a nuanced understanding of its morphological differences and molecular affinities, enriching our comprehension of the diversity and evolutionary relationships of Mazaceae.

[A Review of High-altitude Hypoxia Adaptation and Hypoxic Solid Tumor].

Historically, the Cambrian explosion was a major life evolution event caused by changes of natural environmental oxygen concentration. The use of oxygen was part of the basic survival instinct of higher life, which evolved a complex regulation system in response to variant levels of oxygen concentration. Hypoxia is one of the typical environmental characteristics in plateau areas. After long-term natural selection in hypoxic conditions, numerous species living in plateau areas have evolved unique mechanisms adapted to hypoxia. Recent studies have found that there are some similarities in adaptation to hypoxia between the animals in highland and different types of human solid tumor cells. Herein, we will summarize recent findings about the hypoxia adaptation evolution in high-altitude animals and the characteristics of hypoxic solid tumors, especially the reactive oxygen species responses in hypoxic solid tumors. We believe that deciphering the underlying molecular mechanisms involved in hypoxia adaptation in highland will facilitate the identification of new genes or biomarkers critical for research on hypoxic solid tumors in the future.

Convergent genomic signatures of high-altitude adaptation among domestic mammals.

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the EPAS1 gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the gene C10orf67, which underwent positive selection in three of the domestic mammals. Our data provide an insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway.

Complete plastid genome of Holcoglossum tsii (Orchidaceae, Aeridinae) and phylogenetic analysis.

The complete plastid genome of Holcoglossum tsii was determined and analyzed in this work. The plastome was 146,897 bp in length with 83,366 bp of the large single-copy (LSC) region, 11,957 bp of the small single-copy (SSC) region, and 25,787 bp of the invert repeats (IR) regions. The genome contained 127 genes, 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Phylogenetic analysis suggested H. tsii is sister to H. rupestre.

Effects of paternal electromagnetic pulse exposure on the reproductive endocrine function of male offspring: a pilot study.

Many studies indicate that parental exposure to an electromagnetic field (EMF) can cause long-term toxicity to the health of the offspring. While concerns have been focused on maternal influence, much less is known regarding the effects of paternal factors. Electromagnetic pulse (EMP) is a special and widely used type of EMF. The present study was designed to investigate the effects of paternal EMP exposure on the reproductive endocrine function of the male rat offspring. Male Sprague Dawley rats were randomly exposed to EMP at 200 kV m-1 for 0, 100 or 400 pulses before mating. The adult male offspring were sacrificed and the structural changes of testes, levels of serum steroid hormones, sperm characteristics, reproductive behaviors, content of the reproductive endocrine-related neurotransmitter GABA and expression of the GABAA receptor were analyzed. The results showed that paternal exposure induced a decrease of testosterone (T), sperm quantity and acrosin activity in the male offspring (p < 0.05). It did not show significant changes in the structure of testes, sperm deformity frequency and reproductive behaviors compared with the sham-exposed group. The content of GABA and the protein and mRNA expression of the hypothalamic GABAA receptor protein increased in the EMP exposure group (p < 0.05). In conclusion, our study shows that under these experimental conditions EMP had a certain degree of influence on the reproductive endocrine function of the male rat offspring, and the hypothalamic GABAA receptor may be involved in the reproductive toxicity of the male offspring.

GRK5 functions as an oncogenic factor in non-small-cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide, and non-small-cell lung cancer (NSCLC) accounts for about 80% of all cases, which is the major subgroup of lung cancer. G protein-coupled receptor kinase 5 (GRK5) has been demonstrated to play pivotal roles in both development and progression of several pathological conditions including cancer. Here, we found that GRK5 expression was significantly increased in 539 NSCLC cancerous tissues than that in 99 normal non-cancerous tissues by immunohistochemistry analysis; we also showed intensive higher positive staining percentage in female and adenocarcinoma (ADC) NSCLC patients than that in male and squamous cell carcinoma (SCC) patients, respectively. In addition, GRK5 high expression NSCLC patients had a worse overall survival rate than the low expression patients. We provided evidence showing that both the mRNA and protein expression levels of GRK5 were increased in NSCLC cancerous cell lines (GLC-82, SPC-A-1, H520, H838, H358, A549, and H1299) comparing with that in normal human bronchial epithelium cell line (BEAS-2B), and identified many GRK5 mutations in NSCLC cancerous tissues. In addition, we found that depletion of GRK5 inhibited NSCLC cancerous cell proliferation, migration in vitro, and xenograft tumor formation in vivo. Furthermore, GRK5 knockdown promoted cell cycle arrest at G2/M phase and induced cellular apoptosis. In summary, our data reveal an oncogenic role of GRK5 in NSCLC progression, indicating that GRK5 could be used as a new therapeutic target in future.

Establishment of basal cell carcinoma animal model in Chinese tree shrew (Tupaia belangeri chinensis).

Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog (Hh) signaling pathway has been identified in most BCCs. The treatment of locally advanced and metastatic BBCs is still a challenge and requires a better animal model than the widely used rodents for drug development and testing. Chinese tree shrews (Tupaia belangeri chinensis) are closely related to primates, bearing many physiological and biochemical advantages over rodents for characterizing human diseases. Here, we successfully established a Chinese tree shrew BCC model by infecting tail skins with lentiviral SmoA1, an active form of Smoothened (Smo) used to constitutively activate the Hh signaling pathway. The pathological characteristics were verified by immunohistochemical analysis. Interestingly, BCC progress was greatly enhanced by the combined usage of lentiviral SmoA1 and shRNA targeting Chinese tree shrew p53. This work provides a useful animal model for further BCC studies and future drug discoveries.

A Normalization-Free and Nonparametric Method Sharpens Large-Scale Transcriptome Analysis and Reveals Common Gene Alteration Patterns in Cancers.

Heterogeneity in transcriptional data hampers the identification of differentially expressed genes (DEGs) and understanding of cancer, essentially because current methods rely on cross-sample normalization and/or distribution assumption-both sensitive to heterogeneous values. Here, we developed a new method, Cross-Value Association Analysis (CVAA), which overcomes the limitation and is more robust to heterogeneous data than the other methods. Applying CVAA to a more complex pan-cancer dataset containing 5,540 transcriptomes discovered numerous new DEGs and many previously rarely explored pathways/processes; some of them were validated, both in vitro and in vivo, to be crucial in tumorigenesis, e.g., alcohol metabolism (ADH1B), chromosome remodeling (NCAPH) and complement system (Adipsin). Together, we present a sharper tool to navigate large-scale expression data and gain new mechanistic insights into tumorigenesis.

NCAPH plays important roles in human colon cancer.

Colon cancer (CC) is one of the major malignancies worldwide, whose pathogenesis is complex and requires the accumulated alteration of multiple genes and signaling pathways. Condensins are multi-protein complexes that play pivotal roles in chromosome assembly and segregation during mitosis, meiosis and even tumorigenesis. Using tissue microarrays by immunohistochemistry and hematoxylin-eosin staining, we found that non-SMC condensin I complex subunit H (NCAPH) in colon cancerous tissues was higher than that in all corresponding adjacent non-cancerous tissues. We then characterized the exact function of the NCAPH in CC. We provided evidences showing that NCAPH is highly expressed in colorectal cancer cell lines comparing with normal human colonic epithelial cells, and identified many NCAPH mutations in CC patients. We found that depletion of NCAPH inhibits CC cell proliferation, migration in vitro and xenograft tumor formation in vivo. Furthermore, NCAPH knockdown promotes cell apoptosis and cell cycle arrest at G2/M phase. Interestingly, the NCAPH high expression in tumor tissues of colon patients had a significantly better prognosis and survival rate than low-expression patients, suggesting that NCAPH high expression promotes colonic cancerous cell proliferation; on the other hand, it may also sensitize these cells responding to chemo- or radio-therapies. Collectively, these findings reveal an important role of NCAPH in CC, indicating that NCAPH could be used as a new therapeutic target in future.

Genomic analysis of snub-nosed monkeys (Rhinopithecus) identifies genes and processes related to high-altitude adaptation.

The snub-nosed monkey genus Rhinopithecus includes five closely related species distributed across altitudinal gradients from 800 to 4,500 m. Rhinopithecus bieti, Rhinopithecus roxellana, and Rhinopithecus strykeri inhabit high-altitude habitats, whereas Rhinopithecus brelichi and Rhinopithecus avunculus inhabit lowland regions. We report the de novo whole-genome sequence of R. bieti and genomic sequences for the four other species. Eight shared substitutions were found in six genes related to lung function, DNA repair, and angiogenesis in the high-altitude snub-nosed monkeys. Functional assays showed that the high-altitude variant of CDT1 (Ala537Val) renders cells more resistant to UV irradiation, and the high-altitude variants of RNASE4 (Asn89Lys and Thr128Ile) confer enhanced ability to induce endothelial tube formation in vitro. Genomic scans in the R. bieti and R. roxellana populations identified signatures of selection between and within populations at genes involved in functions relevant to high-altitude adaptation. These results provide valuable insights into the adaptation to high altitude in the snub-nosed monkeys.

Pulsed electromagnetic wave exposure induces ultrastructural damage and upregulated expression of heat shock protein 70 in the rat adenohypophysis.

The aim of the present study was to investigate the ultrastructural damage and the expression of heat shock protein 70 (HSP70) in the rat adenohypophysis following pulsed electromagnetic wave (PEMW) exposure. The rats were randomly divided into four groups: Sham PEMW exposure, 1 x 10(4) pulses of PEMW exposure, 1 x 10(5) pulses of PEMW exposure and 3 x 10(5) pulses of PEMW exposure. Whole body radiation of 1 x 10(4) pulses, 1 x 10(5) pulses and 3 x 10(5) pulses of PEMW were delivered with a field strength of 100 kV/m. The rats in each group (n=6 in each) were sacrificed 12, 24, 48 and 96 h after PEMW exposure. Transmission electron microscopy was then used to detect the ultrastructural changes and immunocytochemistry was used to examine the expression of HSP70. Cellular damage, including mitochondrial vacuolation occurred as early as 12 h after PEMW exposure.More severe cellular damages, including cell degeneration and necrosis, occurred 24 and 48 h after PEMW exposure. The PEMW-induced cellular damage increased as the number of PEMW pulses increased. In addition, the expression of HSP70 significantly increased following PEMW exposure and peaked after 12 h. These findings suggested that PEMW induced ultrastructural damages in the rat adenohypophysis and that HSP70 may have contributed to the PEMW-induced adenohypophyseal damage.

Metabolites from the mushroom Ganoderma lingzhi as stimulators of neural stem cell proliferation.

Ganoderma lingzhi is a valuable, edible and medicinal fungus that has been widely used for the prevention and treatment of a broad range of diseases. In this study, spirolingzhines A-D, four meroterpenoids with a spiro[benzofuran-2,10-cyclopentane] motif, lingzhines A-F, six meroterpenoids with diverse ring systems, along with two known compounds were isolated from the fruiting bodies of this fungus. The structures and stereochemistry of these substances were determined by using spectroscopic, X-ray crystallographic and computational methods. Chiral HPLC was used to separate (-)- and (+)-antipodes of seven of ten meroterpenoids, which were isolated from the fungus as racemic mixtures. Several of the metabolites were found to promote proliferation of neural stem cells (NSCs) and, as such, they constitute a class of NSC stimulators. The most potent member of this series, (-)-spirolingzhine A, was shown to affect NSC cell cycle progression using the 5-bromo-2-deoxyuridine (BrdU) incorporation assay.

Indole alkaloids with new skeleton activating neural stem cells.

Alstoscholarisines A-E (1-5), five unprecedented monoterpenoid indole alkaloids with 6/5/6/6/6 fused-bridge rings, were isolated from Alstonia scholaris. They promoted adult neuronal stem cells (NSCs) proliferation significantly, in which the most active one (1) functioned from a concentration of 0.1 µg/mL in a dosage-dependent manner. Furthermore, 1 enhanced NSC sphere formation and neurogenic fate commitment through activation of a Wnt signaling pathway and promoted NSC differentiation but did not affect proliferation of neuroblastoma cells.

Fem1b promotes ubiquitylation and suppresses transcriptional activity of Gli1.

The mammalian Fem1b gene encodes a homolog of FEM-1, a protein in the sex-determination pathway of the nematode Caenorhabditis elegans. Fem1b and FEM-1 proteins each contain a VHL-box motif that mediates their interaction with certain E3 ubiquitin ligase complexes. In C. elegans, FEM-1 negatively regulates the transcription factor TRA-1, and functions as an E3 ubiquitin ligase substrate recognition subunit to target TRA-1 for ubiquitylation. TRA-1 is homologous to the mammalian Gli1 protein, a transcription factor that mediates Hedgehog signaling as well as having Hedgehog-independent functions. Whether the interaction between nematode FEM-1 and TRA-1 proteins is conserved, between corresponding mammalian homologs, has not been reported. Herein, we show that Fem1b interacts with Gli1 within cells, and directly binds Gli1. Fem1b also promotes ubiquitylation of Gli1, suppresses transcriptional activation by Gli1, and attenuates an oncogenic Gli1 autoregulatory loop in cancer cells, all dependent on the VHL-box of Fem1b. These findings have implications for understanding the cellular functions of Fem1b, and the regulation of Gli1 oncoprotein activity.

TCTP overexpression is associated with the development and progression of glioma.

Upregulation of translationally controlled tumor protein (TCTP) has been reported in a variety of malignant tumors. However, the impact of TCTP in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of TCTP in glioma patients. Western blot analysis was used to characterize the expression patterns of TCTP in 45 glioma and 22 normal brain tissues. Immunohistochemistry on a tissue microarray containing 127 cases of glioma was performed to analyze the association between TCTP expression and clinicopathological features. Compared with normal brain tissues, TCTP expression was significantly higher in glioma tissues (p <0.001). In addition, high TCTP expression in glioma was significantly associated with advanced pathological grade (p = 0.018). Kaplan-Meier analysis showed that patients with glioma and higher TCTP expression tend to have shorter overall survival time (p <0.001). In multivariate analysis, TCTP expression was proved to be an independent prognostic factor for patients with glioma (p <0.001). In conclusion, this study confirmed the overexpression of TCTP and its association with tumor progression in glioma. It also provided the first evidence that TCTP expression in glioma was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of glioma.

[Tree shrews under the spot light: emerging model of human diseases].

Animal models are indispensible in biomedical research and have made tremendous contributions to answer fundamental questions on human biology, disease mechanisms, and to the development of new drugs and diagnostic tools. Due to the limitations of rodent models in translational medicine, tree shrews (Tupaia belangeri chinensis), the closest relative of primates, have attracted increasing attention in modeling human diseases and therapeutic responses. Here we discuss the recent progress in tree shrew biology and the development of tree shrews as human disease models including infectious diseases, metabolic diseases, neurological and psychiatric diseases, and cancers. Meanwhile, the current problems and future perspectives of the tree shrew model are explored.

[Observation on therapeutic effect of type II early diabetic nephropathies intervened by acupoint thread embedding].

OBJECTIVE: To observe the therapeutic effect of type II early diabetic nephropathies intervened by acupoint thread embedding for strengthening spleen and benefiting kidney. METHODS: Sixty cases of type II early diabetic nephropathies were randomly divided into an acupoint thread embedding group and a routine therapy group, 30 cases in each group. In routine therapy group, western medicine routine therapy was applied to control blood sugar, blood pressure and blood lipid. In acupoint thread embedding group, besides the western medicine routine therapy, thread embedding intervention was given at Pishu (BL 20), Zusanli (ST 36), Shenshu (BL 23) and Yishu (Extra) on both sides as main acupints, and the treatment course was 3 months. Urinary micro-albumin excretion (UAER), total score of TCM syndrome and monitor control indices (blood sugar, blood pressure, blood lipid, urea nitrogen and serum creatinine) in both groups were observed before and after treatment, and the therapeutic effects in both groups were compared. RESULTS: After treatment, the indices of UAER and total score of TCM syndrome were all reduced (P < 0.001, P < 0.01); the reduction in acupoint thread embedding group was more obvious (P < 0.01, P < 0.05); the total effective rate in acupoint thread embedding group was 76.7% (23/30), superior to that of 63.3% (19/30) in routine therapy group (P < 0.05). The blood sugar, blood pressure and blood lipid in both groups were remarkably improved (all P < 0.001) after treatment; the urea nitrogen and creatinine had no notable variation. CONCLUSION: Acupoint thread embedding combined with western medicine routine therapy can not only reduce the urinary micro-albumin excretion of type II early diabetic nephropathies, but also improve the Chinese medicine symptoms and the therapeutic effect is superior to that of simple western medicine routine therapy.

A multilayered approach of Si/SiO to promote carrier transport in electroluminescence of Si nanocrystals.

The electroluminescence (EL) and photoluminescence of Si nanocrystals (Si-nc) from multilayered samples of Si/SiO are investigated. Si-nc are formed within Si and SiO layers after furnace annealing. It is found that the presence of Si interlayers creates extra carrier paths for EL emission. A comparative study is further performed on a multilayered Si/SiO sample and a single-layered one with Si and SiO homogeneously mixed. Both samples have the same ratio of Si to O and the same contents of Si and O. The multilayered sample is found to have higher EL intensity, less turn-on voltage, lower resistance, and higher current efficiency than the single-layered one. The results indicate that Si interlayers in Si/SiO may act as carrier channels, which promote carrier transport and enhance the EL emission of Si-nc.

Plexins are GTPase-activating proteins for Rap and are activated by induced dimerization.

Plexins are cell surface receptors that bind to semaphorins and transduce signals that regulate neuronal development, immune responses, and other processes. Signaling through plexins has been proposed to rely on specific guanosine triphosphatase (GTPase)-activating protein (GAP) activity for R-Ras and M-Ras. Activation of this GAP activity of plexins appears to require simultaneous binding of semaphorin to the plexin extracellular domain and of the Rho GTPases Rac1 or Rnd1 to the cytoplasmic region. However, GAP activity of plexins has eluded detection in several recent studies. We show that the purified cytoplasmic region of plexin uses a noncanonical catalytic mechanism to act as a GAP for Rap, but not for R-Ras or M-Ras. The RapGAP activity of plexins was autoinhibited and was activated by induced dimerization. Biochemical and crystallographic analyses demonstrated that binding of Rho GTPases did not directly contribute to activation of plexin RapGAP activity. Semaphorin stimulated the RapGAP activity of full-length plexin in cells, which was required for plexin-mediated neuronal growth cone collapse. Together, these findings define a pathway for plexin signaling and provide insights into the mechanism for semaphorin-induced activation of plexins.