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Eight new species from China, Cheirostylis chuxiongensis, C. yei, Myrmechis lingulata, M. longii, Bulbophyllum ximaense, B. xizangense, B. retusum and B. pulcherissimum, are described and illustrated. Cheirostylis chuxiongensis differs from C. thailandica by having 5–9 irregular and papillae-like calli on each side in the sac of the lip, epichile with entire lobes, petals narrowly obliquely obovate and an apex that is not recurved. Cheirostylis yei is easily distinguished from its relatives similar by having a long stem, pubescent ovary and sepals, epichile lobes with irregular and undulate margins, a subquadrate callus without teeth in the saccate hypochile. Myrmechis lingulata differs from M. chinensis by having a simple and lanceolate to ligulate lip, glabrous bracts and ovary, oblique and narrowly ovate petals. Myrmechis longii differs from M. pumila by having white-veined leaves, oblong-lanceolate epichile lobes, and viscidium attached to the middle of the caudicle. Bulbophyllum ximaense is easily distinguished from its relatives similar by having distant pseudobulbs, shorter scape, an inflorescence with 9–16 orange-red flowers, shorter lateral sepals with a long acuminate apex, incurved and tubular apical margins, a papillate lip disk and triangular-subulate stelidia. Bulbophyllum xizangense is easily distinguished from its relatives similar by having narrow lanceolate leaves, shorter inflorescence with 1–3 greenish-yellow flowers, falcate-ovoid lateral sepals, a lip with small lateral lobes and 3 keels at the base. Bulbophyllum retusum differs from B. spathulatum by having shorter inflorescence, peduncles with 2 tubular sheaths, dorsal sepals with a retuse apex, lateral sepals with lower edges that are connate to each other and free and divergent toward the apex, obovate petals with an acute or slightly retuse apex. Bulbophyllum pulcherissimum differs from B. lopalanthum by its 5-veined dorsal sepal, ovate-lanceolate lateral sepals, obliquely ovate-oblong petal, erose-toothed margins and obovate lip with a large, oblong basal callus, and an obtuse base. In addition, three species (Bulbophyllum frostii, B. raskotii and B. nematocaulon) are reported for the first time in China.

Tintinnid ciliates, having distributional sensitivity to hydrological changes, have been applied as a useful tool to track the movements of water masses. The Yellow Sea Bottom Cold Water (YSBCW) is one of the most prominent summer oceanographic phenomena in the Yellow Sea. To examine the potential of tintinnid species as a biological indicator of the bottom cold water, the spatial distributions of the ciliates were investigated in the southeastern Yellow Sea during the summers of 2010 and 2020. A dominant species, Tintinnidium primitivum, was found in the bottom cold waters in both years. The temperature and salinity (T–S) diagram for the dominant species distribution was plotted against the T–S range for the YSBCW at low temperatures between 6 and 12 ℃ and salinity between 32 and 33. A positive relationship was shown between T. primitivum and Gammaproteobacteria distribution and negative relationships with photosynthetic pico- and nano-plankton. Further studies on prey and predator relationships between microbial organisms and T. primitivum are required to understand the unique structure and function of microbial food webs in the YSBCW.

Background The incidence of bladder cancer (BCa) in male is approximately three to four times higher than in female, but the oncological outcomes in female patients with BCa are significantly worse than in male patients. Although many biomarkers have been identified in recent decades to predict the prognosis of BCa patients, few of them are able to distinguish the prognosis of BCa patients with gender difference. Aromatase encoded by the CYP19A1 gene catalyzes the conversion of androgens to estrogens. In this study, we investigate the prognosis significance of CYP19A1 expression considering the gender difference in BCa patients from four available public databases. Methods Four available public databases of BCa, including GSE13507, TCGA-BLCA, E-MTAB-4321, and E-MTAB-1803, were utilized in this analysis. The overall survival (OS) and progression-free survival (PFS) in different stages and genders were evaluated using the Kaplan-Meier analysis based on the optimal cut-off values of CYP19A1 expression. Then, Gene Set Enrichment Analysis (GSEA) were further performed to explore the potential biologic pathways by altering CYP19A1 expression in BCa patients. Results The results showed that patients with high CYP19A1 expression had a poorer outcome compared with those with low expression in both BCa cohorts in general. Higher CYP19A1 expression in male patients were significantly associated with shorter survival for either non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC). However, female NMIBC patients with high CYP19A1 expression were identified to have a better prognosis, whereas high CYP19A1 expression in female MIBC patients were significantly associated with poorer survival. The result of the GSEA showed that different outcomes in female and male patients with NMIBC were related to the interaction of CYP19A1 and the cell-cycle-related pathways. Conclusions These findings demonstrated that CYP19A1 expression might have a potential role in distinguishing the prognosis of female BCa patients dependent on tumor stage. Our results provide new insights for aromatase-mediated BCa therapy.

Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling transduction, and tissue homeostasis. Abnormality of mucus expression and structure contributes to biological properties related to human cancer progression. Tumor growth sites induce inhospitable conditions. Many kinds of research suggest that mucins provide a microenvironment to avoid hypoxia, acidic, and other biological conditions that promote cancer progression. Given that the mucus layer captures growth factors or cytokines, we propose that mucin helps to ameliorate inhospitable conditions in tumor-growing sites. Additionally, the composition and structure of mucins enable them to mimic the surface of normal epithelial cells, allowing tumor cells to escape from immune surveillance. Indeed, human cancers such as mucinous carcinoma, show a higher incidence of invasion to adjacent organs and lymph node metastasis than do non-mucinous carcinoma. In this minireview, we discuss how mucin provides a tumor-friendly environment and contributes to increased cancer malignancy in mucinous carcinoma. [BMB Reports 2021; 54(7): 344-355].

Aims The morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited. Here, we evaluated the role and therapeutic value of dual-specificity phosphatase 26 (DUSP26) in CAVD. Methods and results Microarray profiling of human calcific aortic valves and normal controls demonstrated that DUSP26 was significantly up-regulated in calcific aortic valves. ApoE−/− mice fed a normal diet or a high cholesterol diet (HCD) were infected with adeno-associated virus serotype 2 carrying DUSP26 short-hairpin RNA to examine the effects of DUSP26 silencing on aortic valve calcification. DUSP26 silencing ameliorated aortic valve calcification in HCD-treated ApoE−/− mice, as evidenced by reduced thickness and calcium deposition in the aortic valve leaflets, improved echocardiographic parameters (decreased peak transvalvular jet velocity and mean transvalvular pressure gradient, as well as increased aortic valve area), and decreased levels of osteogenic markers (Runx2, osterix, and osteocalcin) in the aortic valves. These results were confirmed in osteogenic medium-induced human valvular interstitial cells. Immunoprecipitation, liquid chromatography-tandem mass spectrometry, and functional assays revealed that dipeptidyl peptidase-4 (DPP4) interacted with DUSP26 to mediate the procalcific effects of DUSP26. High N6-methyladenosine levels up-regulated DUSP26 in CAVD; in turn, DUSP26 activated DPP4 by antagonizing mouse double minute 2-mediated ubiquitination and degradation of DPP4, thereby promoting CAVD progression. Conclusion DUSP26 promotes aortic valve calcification by inhibiting DPP4 degradation. Our findings identify a previously unrecognized mechanism of DPP4 up-regulation in CAVD, suggesting that DUSP26 silencing or inhibition is a viable therapeutic strategy to impede CAVD progression.

Summary Non-muscle myosin IIA plays an important role in cell adhesion, cell migration, and tissue architecture. We previously showed that low activity of the heavy chain of non-muscle myosin II Myh9 is beneficial to LGR5+ intestinal stem cell maintenance. However, the function of Myh9 in adult mouse intestinal epithelium is largely unclear. In this study, we used the inducible Villin-creERT2 knockout approach to delete Myh9 in adult mouse intestinal epithelium and observed that homozygous deletion of Myh9 causes colitis-like morphologic changes in intestine, leads to a high sensitivity to dextran sulfate sodium and promotes colitis-related adenoma formation in the colon. Myh9 deletion disturbs cell junctions and impairs intestinal lumen barrier integrity, promoting the necroptosis of epithelial cells. Consistently, these changes can be partially rescued by Ripk3 knockout. Our results indicate that Myh9 is required for the maintenance of intestinal epithelium integrity and the prevention of cell necroptosis., Graphical abstract, Highlights • Homozygous deletion of Myh9 causes colitis-like phenotypes in intestine • Myh9 deficiency leads to reduced Lgr5+ cell population and Paneth cell dislocation • Myh9 is critical for maintenance of intestinal epithelium integrity • Myh9 deletion results in high sensitivity to DSS and colitis adenomas formation, Wang et al. report that Myh9 is required for maintenance of intestinal epithelial integrity mainly by preventing cell necroptosis and inflammation. Myh9 deficiency leads to cell junction disruption and colitis-like phenotypes and related adenomas development.

The cyanobacterium Arthrospira platensis is regarded as a potential future source of food for humans due to its superior nutritional value compared with many conventional crops. An 8-week feeding trial was conducted to evaluate nutritional and pigmentation effects of whole A. platensis, defatted A. platensis and its lipid extracts in diets for the yellow catfish Pelteobagrus fulvidraco. Four percent whole A. platensis (AP4), 0.4% A. platensis lipid extracts (AL0.4), and 4% defatted A. platensis (AR4) were used as experimental diets, and a diet without any A. platensis was as the control diet (AP0). The AP4 and AL0.4 groups had no effects on the growth performance and feed utilization in yellow catfish; however, the AR4 group was significantly lower than the AP0 group in terms of specific growth rate and feed efficiency (P < 0.05). AP4 and AL0.4 groups significantly increased the body protein of fish (P < 0.05). The skin color was significantly improved in the AP4 and AL0.4 groups, as well as the fish skin and plasma lutein contents (P < 0.05). Correlations between skin color and the lutein contents in liver and muscles were weak, whereas the correlations between skin color and the lutein contents in skin and plasma were significant and strong. The results suggest that whole A. platensis and its lipid extracts can be functional additives to improve whole body protein and skin color of fish, while defatted A. platensis showed no advantage in yellow catfish diets.

SummaryTo study the role of orexin A in the reproductive regulation of Mongolian sheep, ovine ovarian granulosa cells were cultured in vitro. The cells were divided into groups after luteinization, the experimental group was given orexin A and the transcriptome was sequenced together with that of the control group. The different genes related to reproduction were screened out. qRT-PCR, western blot and enzyme-linked immunosorbent assay (ELISA) were used to verify the selected genes and detect the effect on progesterone secretion. In total, 123 differentially expressed genes were obtained by sequencing. Six genes with high expression related to reproduction (PRRT2, ABCG1, SOX4, TBX3, ID1 and ATP8) were screened. The results of qRT-PCR were consistent with those of sequencing; western blot and ELISA were used to verify the protein levels of steroidogenic acute regulatory protein (StAR) and its related PRRT2 and ABCG1, and to detect their effect on progesterone secretion. Validation results were consistent with those of qRT-PCR and sequencing. The experimental group was given orexin A and compared with the control group. Expression of PRRT2 protein was significantly increased (P < 0.05), ABCG1 protein expression was significantly decreased (P < 0.05), StAR expression was significantly increased (P < 0.05), and progesterone secretion was significantly increased (P < 0.05). The results showed that orexin A promoted the expression of StAR by upregulating PRRT2 and downregulating ABCG1, therefore affecting secretion of progesterone. Gene expression characteristics of orexin A affecting progesterone secretion were preliminarily explored; this study provides a theoretical basis for further study on signalling pathways and reproductive regulation in Mongolian sheep.

As planktonic ciliates have been recognized as important players in marine microbial food webs, relevant studies have been conducted in the western coastal waters of the Yellow Sea. However, little is known about ciliate distributions from the eastern coast of the Yellow Sea near the Korean Peninsula. A spring cruise in April 2019 was carried out to investigate vertical and horizontal distributions of ciliate plankton at 18 stations that form three zonal sections in the eastern area. Biological (picoplankton, nanophytoplankton, and mesozooplankton) and hydrological (water temperature and salinity) environments were also analyzed to understand relationships between the ciliate distributions and the environments. High abundance (ca. 2400 cells L−1) of a large ciliate species, Laboea strobila, was observed at the surface water of Stn. 37–5. Abundance peak of large (> 50 μm) ciliates coincided with the peak of mesozooplankton abundance. Spatial distribution of the large ciliates was associated with nanophytoplankton distribution while a smaller (20–50 μm) ciliate group was associated with picoplankton distribution. Therefore, the spring distribution of ciliate plankton in the southeastern coast of the Yellow Sea indicates that food size for the ciliates is one of the important factors controlling ciliate compositions as well as their abundances. Further investigations need to be carried out to understand seasonal differences of ciliate distributions in the eastern Yellow Sea.

There have been no reports regarding nystagmus observed immediately after the end of an acute vertiginous attack in patients with Meniere’s disease. The aim of this study was to demonstrate positional direction-changing nystagmus in patients with Meniere’s disease, and to discuss the mechanism that underlies this nystagmus. Video-nystagmography was recorded in two patients with definite Meniere’s disease, who showed positional direction-changing nystagmus during the period immediately after a vertigo attack. In one patient, video-nystagmographic recording was conducted 5 h after an episode of vertigo attack, and it showed very weak, persistent positional geotropic direction-changing nystagmus. In the other patient, video-nystagmographic recording was conducted 23 h after an episode of vertigo attack, and it showed very weak, persistent positional apogeotropic direction-changing nystagmus. Our patients exhibited very weak, persistent positional direction-changing nystagmus, which was geotropic in one and apogeotropic in the other. This type of positional nystagmus has been reported in other inner ear disorders and it cannot be clearly explained by typical benign paroxysmal positional vertigo. The change in chemical composition and/or electrolyte concentration of the inner ear fluid, although still unclear, may underlie the production of this characteristic nystagmus in these patients.

Liparis aureolabella and L. mengziensis, two new species from the karst region of southwestern China, and L. bingzhongluoensis, a new species from montane region in Yunnan, are described and illustrated. L. aureolabella is easily distinguished from its relatives by having abaxially purple leave with purple reticulate veins prominent adaxially, a lip auriculate at base, and falcate-lanceolate pollinia. Liparis mengziensis is closely related to L. petiolata and L. auriculata, but differs from them by having an ovate to broadly ovate leaf, purple lip and apex connate along the margins. Liparis bingzhongluoensis is similar to Liparis nanlingensis, but the new species is characterized by having a lip with two transparent ridges on its disc, longitudinally concave basal callus and triangular column wings. Phylogenetic analyses based on nuclear ribosomal ITS and plastid matK sequences showed that L. aureolabella and L. mengziensis are nested with L. petiolata or L. auriculata in a monophyletic clade. L. bingzhongluoensis is sister to a clade formed by L. nanlingensis, L. tsii, L. sasakii and L. krameri. Moreover, morphological comparisons strongly support that the three species as separated species newly to science.

Background Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive inborn error that affects phenylalanine (Phe) metabolism. It has a complex phenotype with many variants and genotypes among different populations. Shanxi province is a high-prevalence area of PAHD in China. Methods In this study, eighty-nine PAHD patients were subjected to genetic testing using Sanger sequencing, followed by multiplex ligation-dependent probe amplification analysis (MLPA). Allelic and genotypic phenotype values (APV and GPV, respectively) were used for genotype-based phenotypic prediction. Results Fifty-one types of variants, including three novel forms, were identified. The predominant variant was p.R243Q (22.09%), followed by p.R53H (10.47%), p.EX6-96A > G (9.30%), p.V399V (5.23%) and p.R413P (3.49%). Notably, mild hyperphenylalaninemia (MHP) has a high prevalence in this region (up to 45.76%), and the variant p.R53H was solely observed in patients of MHP. According to the genotype–phenotype prediction, the APV/GPV system was well correlated with the metabolic phenotype of most PAHD patients. Conclusion We have systematically constructed the mutational and phenotypic spectrum of PAH in Shanxi province. Hence, this study will help to further understand the genotype-phenotype associations in PAHD patients, and it may offer more reliable genetic counseling and management.

TIGIT is an emerging novel checkpoint target that is expressed on both tumor-infiltrating T cells and NK cells. Some current investigational antibodies targeting TIGIT have also achieved dramatic antitumor efficacy in late clinical research. Most recently, the relevance of NK cell–associated TIGIT signaling pathway to tumors’ evasion of the immune system has been clearly revealed, which endows NK cells with a pivotal role in the therapeutic effects of TIGIT blockade. In this article, we describe a novel anti-TIGIT monoclonal antibody, AET2010, which was acquired from a phage-displayed human single-chain antibody library through a cell panning strategy. With emphasis on its regulation of NK cells, we confirmed the excellent ex vivo and in vivo antitumor immunity of AET2010 mediated by the NK-92MI cells. Intriguingly, our work also revealed that AET2010 displays a lower affinity but parallel avidity and activity relative to MK7684, an investigational monoclonal antibody from MSD, implying a reasonable balance of potency and potential side effects for AET2010. Together, these results are promising and warrant further development of AET2010.

The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia, and a series of bioinformatics databases were used for variant confirmation and functional prediction. Phenotypic characterization of the members of these families was described, and an in vitro analysis was performed for functional evaluation. Five novel MSX1 heterozygous variants were identified: three missense variants [c.662A>C (p.Q221P), c.670C>T (p.R224C), and c.809C>T (p.S270L)], one nonsense variant [c.364G>T (p.G122*)], and one frameshift variant [c.277delG (p.A93Rfs*67)]. Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P, p.R224C, p.G122*, and p.A93Rfs*67 variants compared to the wild type. Three variants (p.Q221P, p.G122*, and p.A93Rfs*67) were classified as pathogenic or likely pathogenic, while p.S270L and p.R224C were of uncertain significance in the current data. Moreover, we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss. Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.

Flatheads are valuable commercial fish species endemic to the Indo-West Pacific. Due to their economic value and unique biological traits, such as metamorphosis and camouflage, they serve as ideal marine organisms for studies on demersal adaptation and evolution. The brown-spotted flathead (Platycephalus sp.1) is the most widely distributed in the northwestern Pacific. Despite the lack of a valid scientific name, it has been long recognized and exploited in the marine fisheries of China, Japan, and Korea. In the current study, we applied Illumina, PacBio, and Hi-C sequencing to assemble a chromosome-scale genome for this species. The assembled genome was 660.63 Mb long with a scaffold N50 of 28.65 Mb and 100% of the contigs were anchored onto 24 chromosomes. We predicted 22 743 protein-coding genes, 94.8% of which were functionally annotated. Comparative genomic analyses suggested that Platycephalus sp.1 diverged from its common ancestor with Gasterosteus aculeatus ~88.4 million years ago. The expanded gene families were significantly enriched in immune, biosynthetic, and metabolic pathways. Furthermore, three shared Gene Ontology terms and 377 common positively selected genes were identified between flathead and flatfish species, suggesting that these genes may contribute to demersal adaptation in flatheads. The assembled genomic data provide a valuable molecular resource for further research on the biological and adaptive evolution of flathead species.

Neoseiulus bicaudus (Wainstein) (Acari: Phytoseiidae) is a native predatory mite species in Xinjiang, China, and a biological control agent for some small pests, such as Tetranychus turkestani (Acari: Tetranychidae) and Thrips tabaci (Thysanoptera: Thripidae) in greenhouse. However, little is known whether N. bicaudus could be an effective natural enemy of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). A series of laboratory and greenhouse experiments were conducted to evaluate the efficiency of N. bicaudus on B. tabaci. The present data showed that each stage of N. bicaudus demonstrated type II functional response when fed on B. tabaci. The adult females showed the highest consumption rate and attack rate, and the shortest handling times were obtained when they preyed on eggs and 1st instar nymphs. The 1st instar of B. tabaci was preferred for the feeding of N. bicaudus adult females than eggs, followed by 2nd instar nymphs of B. tabaci. Under greenhouse conditions, this predator effectively suppressed the population growth of B. tabaci throughout the experimental period. Accordingly, N. bicaudus could be an efficient predator for B. tabaci.

Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment., Cancer: Boosting the right signals to suppress tumors Tumor cells killed by radiotherapy or chemotherapy release signaling molecules that stimulate both immune response and tumor aggressiveness; regulating these molecules could improve treatment efficacy. Tae Heung Kang, Yeong-Min Park, and co-workers at Konkuk University, Seoul, South Korea, have reviewed the role of damage-associated molecular patterns (DAMPs) in immunity and cancer. These signaling molecules act as danger signals, activating immune cells by binding to specific receptors. However, tumor cells have the same receptors, and DAMPs binding triggers chemoresistance and increases invasiveness. The researchers report that although DAMPs can trigger a helpful immune response, they can also cause chronic inflammation, which in turn promotes an immune suppression response, allowing tumors to escape immune detection. Improving our understanding of the functions of different DAMPs could improve our ability to boost the immune response and decrease tumor aggressiveness.

Four halophilic archaeal strains, designated HD8-83T, LYG-36T, DLLS-82 and RC-68T, were isolated from the salted brown alga Laminaria of three different origins (Dalian, Lianyungang, Dalian and Rongcheng) in PR China. All strains had pleomorphic rod cells that were motile, lysed in distilled water, stained Gram-negative, and formed red-pigmented colonies on agar plate (except for DLLS-82, which formed white colonies). Based on phylogenetic analyses of the 16S rRNA genes, strain HD8-83T was closely related to Halorussus litoreus HD8-51T (97.9 % similarity), strain LYG-36T and DLLS-82 to Halorussus rarus TBN4T (94.4 % and 94.7 % similarities, respectively), and strain RC-68T to Halorussus salinus YJ-37-HT (96.9 % similarity). Results of phylogenetic analyses based on rpoB′ genes and 728 concatenated single-copy orthologous clusters also showed that these strains formed three different branches and clustered tightly with the Halorussus members. The average nucleotide identity, average amino acid identity and in silico DNA–DNA hybridization values between strains LYG-36T and DLLS-82 were 98.9, 98 and 92.4%, showing that they were different strains of the same species. While those values between the isolates and other Halorussus members were below 84.7, 82.9 and 28.9 %, respectively. Based on the phenotypic, chemotaxonomic and phylogenetic properties, strains HD8-83T, LYG-36T, DLLS-82 and RC-68T represent three novel species of the genus Halorussus for which the names Halorussus halobius sp. nov. (type strain: HD8-83T=CGMCC 1.15334T=JCM 31110T), Halorussus marinus sp. nov. (type strain: LYG-36T=CGMCC 1.13606T=JCM 32952T; reference strain: DLLS-82=CGMCC 1.13604=JCM 32951) and Halorussus pelagicus sp. nov. (type strain: RC-68T=CGMCC 1.13609T=JCM 32953T) are proposed.

Genes associated with the WNT pathway play an important role in the etiology of tooth agenesis. Low-density lipoprotein receptor–related protein 6 encoding gene ( LRP6) is a recently defined gene that is associated with autosomal dominant inherited tooth agenesis. Here, we aimed to identify novel LRP6 mutations in patients with tooth agenesis and investigate the significance of Lrp6 during tooth development. Using whole-exome sequencing, we identified 4 novel LRP6 heterozygous mutations (c.2292G>A, c.195dup, c.1095dup, and c.1681C>T) in 4 of 77 oligodontia patients. Notably, a patient who carried a nonsense LRP6 mutation (c.2292G>A; p.W764*) presented a hypohidrotic ectodermal dysplasia phenotype. Preliminary functional studies, including bioinformatics analysis and TOP-/FOP-flash reporter assays, demonstrated that the activation of WNT/β-catenin signaling was compromised as a consequence of LRP6 mutations. RNAscope in situ hybridization revealed dynamic and special changes of Lrp6 expression during murine tooth development from E11.5 to E16.5. It was noteworthy that Lrp6 was specifically expressed in the epithelium at E11.5 to E13.5 but was expressed in both dental epithelium and dental papilla from E14.5 and persisted in both tissues at later stages. Our study broadens the mutation spectrum of human tooth agenesis and is the first to identify a LRP6 mutation in patients with hypohidrotic ectodermal dysplasia and reveal the dynamic expression pattern of Lrp6 during tooth development. Information from this study is conducive to understanding the functional significance of Lrp6 on the biological process of tooth development.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that play a critical immunosuppressive role in the tumour micro-environment. Although biological research on MDSCs has made progress, the relationship between the secretion of cytokines by MDSCs and poor prognosis is not clear, and there are no criteria to measure the functional status of MDSCs. Here, we detected the mRNA expression of IL-10, IL-12, TGF-β and TNF-α in MDSCs and the levels of these cytokines in MDSC culture supernatants of patients with myelodysplastic syndromes, and quantified the functional status of MDSCs by IL-10/IL-12 ratio and TGF-β/TNF-α ratio. We found that the ratio of IL-10/IL-12 and TGF-β/TNF-α was significantly higher in higher-risk MDS than in lower-risk MDS and normal control groups. The TGF-β/TNF-α ratio in MDSCs was positively correlated with the percentage of blast cells and was negatively correlated with the percentage of CD3+CD8+ T lymphocytes. Meanwhile, the TGF-β/TNF-α ratio was higher in patients with a lower absolute neutrophil count. It suggested that MDSCs in higher-risk MDS have a stronger immunosuppressive effect and might be related to poor prognosis. Quantifying the functional status of MDSCs with IL-10/IL-12 and TGF-β/TNF-α ratio might help to evaluate the balance of cellular immunity of MDSCs in MDS.

The present study was carried out to evaluate the hematology, serum biochemistry, immune responses and oxidative damage of growing beagles fed a diet supplemented with housefly (Musca domestica) maggot meal (MM). Weanling beagles (initial body weight 2.69 ± 0.17 kg) were fed a control diet (0% MM) or experimental diet (5% MM) for 42 days. The results indicated that the diet supplemented with 5% MM had no significant effects on the hematology and serum biochemistry of growing beagles (P>0.05). Meanwhile, neither the serum concentrations of lysozyme and C-reactive protein nor the serum antibody responses to canine distemper virus and canine parvovirus were influenced by dietary MM supplementation (P>0.05). However, dogs in the experimental group had lower serum levels of malondialdehyde and protein carbonyl than those in the control group (P

Around 6.000 plant species in China have ornamental uses. This study aims to identify new ornamental plant species that are able to survive in urban environments of China and not stand out from the landscaping plants growing in the local parks, gardens, and walkways. The list of ornamental plants includes exclusively open-ground plants. The study on 29 wild plant species commonly found across Southern China involved growing plants from 9.200 seeds and measuring their survival at the first (herbals) and the fifth 5 year of age (shrubs and trees). Of all study plants, 16 showed high germination and survival rates (over 50%) and can be used in park and city landscaping, whereas other specimens demonstrated survival rates lower than 50%. For lianas, the number of species suitable for landscaping is 3. Low germination rates did not determine a rapid decline in survival during the first and fifth years. Herbals turned out to have the highest germination rates (over 50% in 6 out of 7 specimens). Among trees, species that may be planted together along sidewalks to form groves and plantations include Ilex latifolia, Delavaya toxocarpa, and Vernicia fordii. Among vines, Trachelospermum jasminoides or star jasmine can be used as a tree climber. Among shrubs and herbals, Melastoma dodecandrum and Corydalis edulis can be planted in flower beds and rock gardens. This work examines plant species not only from the decorative prospective but also in terms of suitability for growing in urban conditions.

Nonsyndromic oligodontia is a rare congenital anomaly. Mutations in the ectodysplasin A receptor (EDAR) gene are the primary cause of hypohidrotic ectodermal dysplasia but are rarely reported in nonsyndromic oligodontia. This study investigated EDAR mutations in multiplex nonsyndromic oligodontia and comparatively analyzed the EDAR- and EDA-related tooth agenesis patterns. Mutation screening was carried out using whole-exome sequencing and familial segregation. Evolutionary conservation and conformational analyses were used to evaluate the potential pathogenic influence of EDAR mutants. EDAR mutations were found to occur in 10.7% of nonsyndromic oligodontia cases. We reported seven heterozygous mutations of EDAR, including five novel mutations (c.404G>A, c.871G>A, c.43G>A, c.1072C>T, and c.1109T>C) and two known mutations (c.319A>G and c.1138A>C). Genotype-phenotype correlation analysis demonstrated that the EDAR-related tooth agenesis pattern was markedly different from EDA. The mandibular second premolars were most frequently missing (57.69%) in EDAR-mutated patients. Our results provide new evidence for the genotypic study of nonsyndromic oligodontia and suggest that EDAR haploinsufficiency results in nonsyndromic tooth agenesis. Furthermore, the distinct pattern between EDAR- and EDA-related tooth agenesis can be used as a guide for mutation screening during the clinical genetic diagnosis of this genetic disorder.

Previous nutritional studies have shown that insulin regulation is different between DT and A strains of gibel carp. As leptin plays a pivotal role in the effects of insulin, we hypothesised that leptin regulation of glucose and lipid metabolism would differ between the two strains. To test our hypothesis, recombinant human leptin was injected into two strains. The results showed that leptin activated the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (AKT), AMP-activated protein kinase–acetyl coenzyme A carboxylase and Janus kinase 2 (JAK2)–signal transducer and activator of transcription (STAT) signalling pathways in both strains. Hypoglycaemia induced by leptin might be due to higher glucose uptake by the liver and muscles together with enhanced glycolytic potential and reduced gluconeogenic potential. Decreased lipogenesis and up-regulated fatty acid oxidation were induced by leptin. In terms of genotype, the PI3K–AKT signalling pathway was more strongly activated by leptin in the muscle tissue of the A strain, as reflected by the heightened phosphorylation of AKT. Furthermore, glycogen content, glycolytic enzyme activity and gluconeogenic capability were higher in the A strain than the DT strain. Strain A had higher levels of fatty acid synthesis and lipolytic capacity in the liver than the DT strain, but the opposite was true in white muscle. Regarding leptin–genotype interactions, the DT strain displayed stronger regulation of glucose metabolism in the liver by leptin as compared with the A strain. Moreover, a more active JAK2–STAT signalling pathway accompanied by enhanced inhibition of fatty acid synthesis by leptin was observed in the DT strain. Overall, the regulation of glucose and lipid metabolism by leptin differed between the two strains, as expected.

Background/Aims: The treatment options for Helicobacter pylori (H. pylori) infection are in a state of flux: traditional triple therapies have started to fail, and new treatments are unable to achieve optimal eradication rates. Rifaximin and rifabutin are new antibiotics. The aim of this study was to evaluate the efficacy and safety of adding rifaximin to the standard triple regimen and of a rifabutin-based triple regimen as a rescue therapy for H. pylori eradication.Materials and Methods: We enrolled 27 H. pylori-positive patients who were treated with a proton pump inhibitor, amoxicillin, clarithromycin, and rifaximin for 14 days. H. pylori eradication was assessed by a 13C-urea breath test performed 4 weeks after therapy completion. The efficacy of the therapy was based on intention-to-treat (ITT) and per-protocol (PP) analysis. We also investigated the resistance rate, compliance, and side effects associated with rifaximin therapy. Minimal inhibitory concentrations and resistance to rifabutin were evaluated using the agar dilution method.Results: Of the 27 patients, 22 completed the treatment protocol with 100% compliance; five patients withdrew. The ITT and PP eradication rates for the rifaximin-containing quadruple therapy were 70.4% (19/27) and 86.3% (19/22), respectively. Adverse events were observed in five of 22 patients (22.7%). The resistance rates to rifaximin and rifabutin were 66.7% (2/3) and 0% (0/3), respectively.Conclusions: The findings of this study show the limitations of rifaximin-based quadruple therapy and suggest the benefits of a rifabutin-based rescue regimen in South Korea.

FOXA1 functions as a pioneer transcription factor by facilitating the access to chromatin for steroid hormone receptors, such as androgen receptor and estrogen receptor1-4, but mechanisms regulating its binding to chromatin remain elusive. LSD1 (KDM1A) acts as a transcriptional repressor by demethylating mono/dimethylated histone H3 lysine 4 (H3K4me1/2)5,6, but also acts as a steroid hormone receptor coactivator through mechanisms that are unclear. Here we show, in prostate cancer cells, that LSD1 associates with FOXA1 and active enhancer markers, and that LSD1 inhibition globally disrupts FOXA1 chromatin binding. Mechanistically, we demonstrate that LSD1 positively regulates FOXA1 binding by demethylating lysine 270, adjacent to the wing2 region of the FOXA1 DNA-binding domain. Acting through FOXA1, LSD1 inhibition broadly disrupted androgen-receptor binding and its transcriptional output, and dramatically decreased prostate cancer growth alone and in synergy with androgen-receptor antagonist treatment in vivo. These mechanistic insights suggest new therapeutic strategies in steroid-driven cancers.

Purpose Citrate synthase (CS) is a rate-limiting enzyme in the citrate cycle and is capable of catalyzing oxaloacetate and acetyl-CoA to citrate. CS has been uncovered to be upregulated in a variety of cancers, and its expression and clinical significance in prostate cancer (PCa) remain unknown. Methods In this study, we examined the association between CS expression level and clinicopathological features of prostate cancer patients in a TMA cohort and the public cancer database (The Cancer Genome Atlas-Prostate Adenocarcinoma, TCGA-PRAD). The CS knockdown cell lines were constructed to study the effects of CS downregulation on proliferation, colony formation, migration, invasion, and cell cycle of prostate cancer cells in vitro. And the effect of CS downregulation on tumor growth in mice was studied in vivo. In addition, the metabolomics and mitochondrial function were detected in the CS knockdown cell lines. Results CS expression level in PCa tissues was higher than that in normal tissues (P < 0.05). CS upregulation was significantly associated with high Gleason score (P < 0.05), advanced pathological stage (P < 0.001), and biochemical recurrence (P < 0.001). Functionally, decreased expression of CS inhibited PCa cell proliferation, colony formation, migration, invasion and cell cycle in vitro, and inhibited tumor growth in vivo. In addition, CS downregulation exerted potential inhibitory effects on the lipid metabolism and mitochondrial function of PCa cells. Conclusion In conclusion, these findings suggested that CS upregulation may contribute to the aggressive progression and poor prognosis of PCa patients, which might be partially associated with its influences on the cell lipid metabolism and mitochondrial function.

This study was carried out to obtain information on the developmental biology and the management of biological resources of the abalone Haliotis gigantea in Korea. The sex ratio (female:male) in the present study was 1:1.7 and the proportion of females was 36.6% (n=106/290). Their gonadal structures displayed definitive seasonal changes which were similar in pattern to the changes in the gonad index (GI). The GI showed a pattern of definitive seasonal changes in both males and females it was high in the fall and low in the spring. The reproductive cycle could be categorized into the following six stages: inactive, early active, late active, ripe, spent, and degenerative stage. Based on the monthly changes in GI and stages of gonadal development, October to November was determined to be the main spawning period for H. gigantea on Jeju Island, Korea.

In Orchidaceae, pollination is mostly animal-mediated, and one-third of species have evolved a deceptive pollination mechanism without rewards. Cypripedium is a representative lineage of nonrewarding orchids restricted to temperate regions. Cypripedium subtropicum flowers are pollinated by hoverflies and have hairy tufts that visually resemble an aphid colony covered with honey dew. We recorded the behavior of hoverflies on the flowers, determined the breeding system of the species and the structure of hairy tufts, and investigated the roles of hairy tufts and floral volatiles in this specialized pollination by using pollination experiments, scanning electron microscopy, bioassays and chemical analyses. The white hairy tufts covering the sidelobes of the labellum provide edible rewards and serve as crucial visual lures for hoverflies. The flowers emit primarily (E)-β-farnesene and a smaller amount of β-pinene that were found to attract hoverflies. Our results suggest that C. subtropicum uses both visual mimicry of an aphid-colonized labellum with a reward and chemical mimicry of aphid alarm pheromones to attract hoverflies for pollination. This is the first described example of a rewarding mimicry system in plants, where the models are animals with their secretions and the reward is similar in nutrients to that of the model mimicked.

A novel Gram-stain-negative, aerobic and rod-shaped halophilic archaeon, designated HD8-45T, was isolated from the red brine of salted brown alga Laminaria produced at Dalian, PR China. According to the results of 16S rRNA gene and rpoB′ gene sequence comparisons, strain HD8-45T showed the highest sequence similarity to the corresponding genes of Salinirussus salinus YGH44T (95.1 and 85.2 % similarities, respectively), Halovenus aranensis EB27T (91.2 and 86.0 % similarities, respectively). The low sequence similarity and the phylogeny implied the novel generic status of strain HD8-45T. Genomic relatedness analyses showed that strain HD8-45T were clearly distinguished from other species in the order Halobacteriales , with average nucleotide identity, amino acid identity and in silico DNA–DNA hybridization values not more than 75.1, 65.6 and 21.5 %. The polar lipid pattern contained phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, two major glycolipids and two minor glycolipids. The two major glycolipids and a minor glycolipid were chromatographically identical to disulfated mannosyl glucosyl diether, sulfated mannosyl glucosyl diether and mannosyl glucosyl diether, respectively. The major respiratory quinones were menaquinone MK-8 and MK-8(H2). The DNA G+C content was 62.0 mol% (Tm ) and 61.9 mol% (genome). All these results showed that strain HD8-45T represents a novel species of a new genus in the order Halobacteriales , for which the name Salinibaculum litoreum gen. nov., sp. nov. is proposed. The type strain of Salinibaculum litoreum is HD8-45T (=CGMCC 1.15328T=JCM 31107T).

Three rod-shaped halophilic archaeal strains, DL-M4T, LYG-109 and DLLS-108T, were isolated from the salted brown alga Laminaria produced in different marine areas of PR China. Cells of strains were motile, formed red-pigmented colonies on agar and lysed in distilled water. The three strains grew optimally with 2.6 M NaCl, with 0.05–0.3 M MgCl2, at 37 °C and at pH 7.0–7.5. The results of phylogenetic analyses based on the 16S rRNA and rpoB′ genes differentiated these strains into two clusters belonging to the genus Halostella , which currently contains Halostella salina CBA1114T and Halostella limicola LT12T. Strains DL-M4T and LYG-109 formed a single cluster separate from the current two members of Halostella (94.4–95.7 and 90.0–90.9 % similarities, respectively) while strain DLLS-108T had Hsl. salina CBA1114T as its nearest neighbour (97.7–97.8 and 95.9 % similarities, respectively) and was separated from Hsl. limicola LT12T (94.4–95.8 and 93.4 % similarities, respectively). These clusters represented two distinct novel species as indicated by phenotypic characteristics, polar lipid compositions and whole-genome comparisons. Diverse phenotypic characteristics, morphology and growth characteristics, nutrition and miscellaneous biochemical tests differentiate strains DL-M4T, LYG-109, DLLS-108T from Hsl. limicola LT12T and Hsl. salina CBA1114T. Strains DL-M4T and LYG-109 contained phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and three unidentified glycolipids, while strain DLLS-108T contained these polar lipids and two unidentified phospholipids. The major respiratory quinones detected in the three isolates were menaquinone MK-8 and MK-8(H2). The average nucleotide identity (ANI) and in silico DNA–DNA hybridization (isDDH) values between the isolated strains and the current two members of Halostella were found to be 79.3–86.6 (ANI) and 22.9–49.8 % (isDDH). All these results showed that the three isolates represent two novel species of the genus Halostella for which the names Halostella pelagica sp. nov. [type strain dl-M4T (=CGMCC 1.13603T=JCM 32954T)] and Halostella litorea sp. nov. [type strain DLLS-108T(=CGMCC 1.13610T=JCM 32955T)] are proposed.

Cryptophytes are a ubiquitous algal group and are important primary producers in aquatic ecosystems. Identification of lineages within the group is difficult because of their simple morphology and ...

WNT10A (Wingless-type MMTV integration site family, member 10A) plays a crucial role in tooth development, and patients with biallelic WNT10A mutation and mice lacking Wnt10a show taurodontism. However, whether epithelial or mesenchymal WNT10A controls the initiation of the root furcation formation remains unclear, and the functional significance of WNT10A in regulating root morphogenesis has not been clarified. Here, we investigated how Wnt10a affects tooth root development by generating different tissue-specific Wnt10a conditional knockout mice. Wnt10a knockout in the whole tissue ( EIIa-Cre;Wnt10aflox/flox) and in dental epithelium ( K14-Cre;Wnt10aflox/flox) led to an absence of or apically located root furcation in molars of mice, a phenotype that resembled taurodontism. An RNAscope analysis showed that the dynamic epithelial and mesenchymal Wnt10a expression pattern occurred during root development. Immunofluorescent staining of E-cadherin and EdU revealed decreased epithelial cell proliferation at the cervical region of the molar in K14-Cre;Wnt10aflox/floxmice at postnatal day 0 (PN0), just before the initiation of root morphogenesis. Interestingly, we found increased pulpal mesenchymal cell proliferation in the presumptive root furcating region of the molar in K14-Cre;Wnt10aflox/floxmice at PN4 and PN7. RNA-seq indicated that among the Wnt ligands with high endogenous expression levels in molars, Wnt4 was increased after epithelial knockout of Wnt10a. The RNAscope assay confirmed that the expression of Wnt4 and Axin2 in the dental papilla of the presumptive root furcating region, where dental pulp overgrowth occurred, was increased in K14-Cre;Wnt10aflox/floxmolars. Furthermore, after suppression of the elevated Wnt4 level in K14-Cre;Wnt10aflox/floxmolars by Wnt4 shRNA adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study provides the first in vivo evidence that epithelial Wnt10a guides root furcation formation and plays a crucial role in controlling the organized proliferation of adjacent mesenchymal cells by regulating proper Wnt4 expression during root furcation morphogenesis.

Breast cancer (BC) is one of the most common cancers in women. TNBC (Triple-negative breast cancer) has limited treatment options and still lacks viable molecular targets, leading to poor outcomes. Recently, RNA-binding proteins (RBPs) have been shown to play crucial roles in human cancers, including BC, by modulating a number of oncogenic phenotypes. This suggests that RBPs represent potential molecular targets for BC therapy. Methods: We employed genomic data to identify RBPs specifically expressed in TNBC. NONO was silenced in TNBC cell lines to examine cell growth, colony formation, invasion, and migration. Gene expression profiles in NONO-silenced cells were generated and analyzed. A high-throughput screening for NONO-targeted drugs was performed using an FDA-approved library. Results: We found that the NONO RBP is highly expressed in TNBC and is associated with poor patient outcomes. NONO binds to STAT3 mRNA, increasing STAT3 mRNA levels in TNBC. Surprisingly, NONO directly interacts with STAT3 protein increasing its stability and transcriptional activity, thus contributing to its oncogenic function. Importantly, high-throughput drug screening revealed that auranofin is a potential NONO inhibitor and inhibits cell growth in TNBC. Conclusions: NONO is an RBP upstream regulator of both STAT3 RNA and protein levels and function. It represents an important and clinically relevant promoter of growth and resistance of TNBCs. NONO is also therefore a potential therapeutic target in TNBC.

An oral starch administration trial was used to evaluate glucose homoeostasis in grass carp (Ctenopharyngodon idella) and Chinese longsnout catfish (Leiocassis longirostrisGünther). Fish were administered with 3 g of a water and starch mixture (with 3:2 ratio) per 100 g body weight after fasting for 48 h. Fish were sampled at 0, 1, 3, 6, 12, 24 and 48 h after oral starch administration. In grass carp, plasma levels of glucose peaked at 3 h but returned to baseline at 6 h. However, in Chinese longsnout catfish, plasma glucose levels peaked at 6 h and returned to baseline at 48 h. The activity of intestinal amylase was increased in grass carp at 1 and 3 h, but no significant change in Chinese longsnout catfish was observed. The activity of hepatic glucose-6-phosphatase fell significantly in grass carp but change was not evident in Chinese longsnout catfish. The expression levels and enzymic activity of hepatic pyruvate kinase increased in grass carp, but no significant changes were observed in the Chinese longsnout catfish. Glycogen synthase (gys) and glycogen phosphorylase (gp) were induced in grass carp. However, there was no significant change ingysand a clear down-regulation ofgpin Chinese longsnout catfish. In brief, compared with Chinese longsnout catfish, grass carp exhibited a rapid increase and faster clearance rate of plasma glucose. This effect was closely related to significantly enhanced levels of digestion, glycolysis, glycogen metabolism and glucose-induced lipogenesis in grass carp, as well as the inhibition of gluconeogenesis.

Clostridium autoethanogenum protein (CAP) is a novel protein source for aqua-feeds. The present study aimed to investigate the effects of dietary CAP on growth performance, immunity, and liver health status of juvenile largemouth bass (Micropterus salmoides). Four isonitrogenous and isolipid experimental diets were formulated to replace 0% (D1, control), 25% (D2), 50% (D3), and 75% (D4) of fish meal by CAP. Fish (15.05 ± 0.08 g) were randomly fed one of four experimental diets for 8 weeks. The results showed that weight gain (WG), specific growth rate (SGR), feeding rate (FR), viscerosomatic index (VSI), and hepatosomatic index (HSI) of the D4 group were significantly lower than D1, D2, and D3 groups (P < 0.05). With the increase of substitution level, the total antioxidant capacity (T-AOC) of liver tissue was significantly decreased, while the plasma alkaline phosphatase (AKP) activity was significantly increased (P < 0.05). Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly higher in D3 and D4 groups than in D1 and D2 groups (P < 0.05). Replacing 50 or 75% fish meal by CAP significantly induced the transcription level of apoptosis-promoting genes (bcl-2-associated death protein [bad] and bcl-2-assoxicated × protein; bag [bax]), anti-apoptosis-related genes (tumor protein 53 [p53] and b-cell lymphoma-2 [bcl-2]), and the apoptotic Caenorhabditis elegans (C. elegans) death gene-3 like caspases (cysteine-aspartic proteases-3 [caspase-3], cysteine-aspartic proteases-8 [caspase-8], cysteine-aspartic proteases-9 [caspase-9], and cysteine-aspartic proteases-10 [caspase-10]) in liver, while suppressed the gene expression of the inflammatory factors [interleukin-1β (il-1β), interleukin-8 (il-8), and tumor necrosis factor, tnf ] in head kidney. At the same time, dietary inclusion of CAP elevated the protein expression of bcl-2, autophagy microtubule-associated protein light chain 3A/B (LC3A/B-I), and LC3A/B-II by inhibiting the phosphorylation of the mammalian target of rapamycin (mTOR; P < 0.05). Moreover, the apoptosis rate of the D3 and D4 groups was significantly increased (P < 0.05). Taken together, these results indicated that the optimal level of CAP-replacing fish meal should be

Low-density lipoprotein receptor-related protein 6 (LRP6) is a pathogenic gene of selective tooth agenesis-7 (OMIM#616724). Although the malformation of the digits and fore- and hindlimbs has been reported in Lrp6-deficient mice, it has been rarely discovered in humans with LRP6 mutations. Here, we demonstrate an unreported autosomal dominant LRP6 heterozygous mutation (c.2840 T > C;p.Met947Thr) in a tooth agenesis family with hand polydactyly, and another unreported autosomal dominant LRP6 heterozygous mutation (c.1154 G > C;p.Arg385Pro) in a non-syndromic tooth agenesis family. Bioinformatic prediction demonstrated the deleterious effects of the mutations, and LRP6 structure changes suggested the corresponding functional impairments. Analysis on the pattern of LRP6-related tooth agenesis demonstrated the maxillary lateral incisor was the most affected. Our study report that LRP6 mutation might be associated with hand preaxial polydactyly in humans, which broaden the phenotypic spectrum of LRP6-related disorders, and provide valuable information on the characteristics of LRP6-related tooth agenesis.

K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.

PURPOSE The purpose of this study was to investigate the correlation between computed tomography imaging characteristics in lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutations. METHODS A total of 124 patients with lung adenocarcinoma and known EGFR mutation status were collected in this retrospective study. Computed tomography quantitative parameters of each tumor, including total volume, total surface, surface-to-volume ratio (SVR), average diameter, maximum diameter, and average density, were determined using computer-aided detection software. The correlation between the EGFR mutation status and imaging characteristics was assessed. The predictive value of these imaging characteristics for EGFR mutation was calculated using the area under the receiver operating characteristic curve. RESULT Fifty-eight of 124 patients showed EGFR mutations. Patients who are female (P < 0.001) and nonsmokers (P < 0.001) and those with serum carcinoembryonic antigen (CEA) level of ≥5 (P = 0.035) were likely to have EGFR mutation. Computed tomography features including air bronchogram (P = 0.035), absence of cavitation (P = 0.010), and absence of pulmonary emphysema (P = 0.002) and quantitative parameters, such as smaller total surface (P = 0.002), smaller total volume (P = 0.001), higher SVR (P = 0.003), and smaller average diameter (P = 0.001), were associated with EGFR mutation. Logistic regression analysis revealed that the most significant independent prognostic factors of EGFR mutation for the model were nonsmoking (P = 0.035), CEA level of ≥5 (P = 0.004), presence of air bronchogram (P = 0.040), absence of cavitation (P = 0.021), and high SVR (P = 0.014). The area under the receiver operating characteristic curve, sensitivity, and specificity of the model for predicting EGFR mutation were 0.827, 75.8%, and 82.8%, respectively. CONCLUSIONS EGFR-mutated adenocarcinoma showed significantly increased CEA level, presence of air bronchogram, absence of cavitation, and higher quantitative parameter SVR than those with wild-type EGFR.

Background Nitrogen, as a limiting factor for net primary productivity in grassland ecosystems, is an important link in material cycles in grassland ecosystems. However, the nitrogen assimilation efficiency and mechanisms of grassland plants under grazing disturbance are still unclear. This study investigated Stipa breviflora desert steppe which had been grazed for 17 years and sampled the root system and leaf of the constructive species Stipa breviflora during the peak growing season under no grazing, light grazing, moderate grazing and heavy grazing treatments. The activities of enzymes related to nitrogen assimilation in roots and leaves were measured. Results Compared with no grazing, light grazing and moderate grazing significantly increased the activities of nitrate reductase (NR), glutamine synthetase (GS), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) in leaves, and GS, GOT and GPT in roots of Stipa breviflora, while heavy grazing significantly decreased the activities of GS in leaves and NR in roots of Stipa breviflora. NR, GOT and GPT activities in leaves and roots of Stipa breviflora were positively correlated with nitrogen content, soluble protein, free amino acid and nitrate content. Conclusions Grazing disturbance changed the activities of nitrogen assimilation related enzymes of grassland plants, and emphasized that light grazing and moderate grazing were beneficial for nitrogen assimilation by grassland plants. Therefore, establishing appropriate stocking rates is of great significance for material flows in this grassland ecosystem and for the stability and sustainable utilization of grassland resources.

ObjectiveMiR-1224 has been reported to exhibit abnormal expression in several tumors. However, the expressing pattern and roles of miR-1224 in gastric cancer (GC) remain unclear. Our current research aimed to explore the potential involvement of miR-1224 in the GC progression.Materials and MethodsThe expression of miR-1224 was examined in tissue samples of 128 GC patients and cell lines by RT-PCR. Besides, the associations of miR-1224 expressions with clinicopathologic features and prognosis of GC patients were analyzed. Then, the possible influences of miR-1224 on cell proliferation and cell migration were determined. Afterward, the molecular target of miR-1224 was identified using bioinformatics assays and confirmed experimentally. Finally, RT-PCR and Western blot assays were performed to investigate the effect of the abnormal miR-1224 expression on the EMT and Wnt/β-catenin pathway.ResultsmiR-1224 was lowly expressed in the GC specimens and cell lines due to T classification and TNM stage. Survival assays demonstrated that GC patients with low expressions of miR-1224 possessed poor overall survivals. Moreover, in vitro and in vivo assays revealed that the overexpression of miR-1224 inhibited cell proliferation, migration, and invasion in GC cells. SATB homeobox 1 (SATB1) was verified as a direct target of miR-1224 in GC. Furthermore, β-catenin and c-myc were significantly inhibited in miR-1224-overexpression cells.ConclusionsOur findings highlight the potential of miR-1224 as a therapeutic target and novel biomarker for GC patients

Hepatitis B virus (HBV) can integrate into the chromosomes of infected hepatocytes, creating potentially oncogenic lesions that can lead to hepatocellular carcinoma (HCC). However, our current understanding of integrated HBV DNA architecture, burden, and transcriptional activity is incomplete due to technical limitations. A combination of genomics approaches was used to describe HBV integrations and corresponding transcriptional signatures in three HCC cell lines: huH-1, PLC/PRF/5, and Hep3B. To generate high-coverage, long-read sequencing data, a custom panel of HBV-targeting biotinylated oligonucleotide probes was designed. Targeted long-read DNA sequencing captured entire HBV integration events within individual reads, revealing that integrations may include deletions and inversions of viral sequences. Surprisingly, all three HCC cell lines contain integrations that are associated with host chromosomal translocations. In addition, targeted long-read RNA sequencing allowed for the assignment of transcriptional activity to specific integrations and resolved the contribution of overlapping HBV transcripts. HBV transcripts chimeric with host sequences were resolved in their entirety and often included >1,000 bp of host sequence. This study provides the first comprehensive description of HBV integrations and associated transcriptional activity in three commonly utilized HCC-derived cell lines. The application of novel methods sheds new light on the complexity of these integrations, including HBV bidirectional transcription, nested transcripts, silent integrations, and host genomic rearrangements. The observation of multiple HBV-associated chromosomal translocations gives rise to the hypothesis that HBV is a driver of genetic instability and provides a potential new mechanism for HCC development. IMPORTANCE HCC-derived cell lines have served as practical models to study HBV biology for decades. These cell lines harbor multiple HBV integrations and express only HBV surface antigen (HBsAg). To date, an accurate description of the integration burden, architecture, and transcriptional profile of these cell lines has been limited due to technical constraints. We have developed a targeted long-read sequencing assay that reveals the entire architecture of integrations in these cell lines. In addition, we identified five chromosomal translocations with integrated HBV DNA at the interchromosomal junctions. Incorporation of long-read transcriptome sequencing (RNA-Seq) data indicated that many integrations and translocations were transcriptionally silent. The observation of multiple HBV-associated translocations has strong implications regarding the potential mechanisms for the development of HBV-associated HCC.

Root zone microbial structure is particularly complex in plants with rhizosheaths, and greater understanding of the rhizosheath may play an important role in the future development of sustainable agricultural practices. However, one important reason to focus study on rhizosheath microbial structure is that there is no definite method for rhizosheath separation. The aim of this study was to explore rhizosheath isolation methods and the diversity characteristics of microorganisms around the rhizosphere. In this study, we isolated the rhizosheath of Stipa grandis, a dominant species in desert steppe, and the microorganisms in the roots, root epidermis, rhizosheath and rhizosphere soil were extracted and sequenced by 16S rRNA and ITS. The alpha diversity index of bacteria in Stipa grandis rhizosphere soil was the greatest, followed by rhizosheath, and the alpha diversity index of endophytic bacteria in root system was the smallest. The alpha diversity index of fungi in the rhizosheath and rhizosphere soil were significantly higher than that in the root epidermis and root system. There were significant differences in bacterial community structure between the root epidermis, endophytic bacteria, rhizosheath and rhizosphere soil. Unlike bacterial community structure, the community structure of fungi in the root epidermis was similar that of endophytic fungi, but significantly different from those in rhizosheath and rhizosphere soil. This study demonstrated a feasible method for separating plant rhizosheath and root epidermis. We suggest that the root epidermis can act as the interface between the host plant root and the external soil environment. We will have to re-examine the biological and ecological significance of rhizosheath and microorganisms in rhizosheath, as well as the mechanism explaining the close relationship of the rhizosheath and the plant root epidermis. This study provides theoretical and technical guidance for the isolation of the plant rhizosheath and the study of microorganisms in plant rhizosheath.

Stress physiology of lactic acid bacteria (LAB) is crucial to their ecological fitness and applicational implications. As a self-imposed stress, lactic acid is the major final metabolic product of LAB and its accumulation can be detrimental to bacterial cells. However, the relationship between LAB carbohydrate metabolism, the primary energy supplying bioactivities, and lactic acid stress responses is not fully understood. Pediococcus pentosaceus has been recognized as an important cell factory and demonstrated probiotic activities. This study investigated behavior of P. pentosaceus under lactic and acetic acid stresses, particularly with supplementations of metabolizable carbohydrates. Lactic and acetic acid retain similar growth stagnation effect, and both resulted in cell death in P. pentosaceus. All metabolizable carbohydrates improved bacterial survival compared to lactic acid control, while xylooligosaccharides (XOS) exerted the highest viability protective efficacy, 0.82 log CFU/mL higher population survived than other carbohydrates after 30 h of incubation. RNA-seq pipeline showcased the intensive global transcriptional responses of P. pentosaceus to lactic acid, which caused significant regulations (more than 2 Log2 fold) of 16.5% of total mRNA coding genes. Glucose mainly led to gene suppressions (83 genes) while XOS led to gene up-regulations (19 genes) under lactic acid stress. RT-qPCR study found that RNA polymerase-centered transcriptional regulation is the primary regulatory approach in evaluated culture conditions. The synergy between lactic acid stress and carbohydrate metabolism should be attentively contemplated in future studies and applications.

Background: Infantile hypotonia with psychomotor retardation and characteristic facies 2 (IHPRF2) is a rare autosomal recessive neurodevelopmental disorder caused by mutations in the UNC80 gene. It is characterized by severe global developmental delay, poor or absent speech and absent or limited walking abilities. The current study explored a case of a Chinese patient with IHPRF2 caused by a novel splicing variant of UNC80.Case Report: The proband is a 8-year-old Chinese male manifested with global developmental delay, severe truncal hypotonia, absent speech and intellectual disability. SNP array analysis revealed a uniparental isodisomy of the entire chromosome 2 [UPD(2)] in the proband. Whole exome sequencing (WES) subsequently identified a novel mutation c.5609-4G>A in the UNC80 gene, which was inherited from his mother and was confirmed by Sanger sequencing, indicating that UPD(2) was of maternal origin.Conclusion: A novel UNC80 homozygous splicing variant c.5609-4G>A associated with maternal UPD(2) was identified. These findings indicate that UPD poses a high risk of autosomal recessive diseases, and provides information on the variant spectrum for UNC80. Our findings elucidate on understanding of the genotype-phenotype associations that occur in IHPRF2 patients.

Myocardial fibrosis (MF) is an important pathological process in which a variety of cardiovascular diseases transform into heart failure. The main manifestation of MF is the excessive deposition of collagen in the myocardium. Here, we explored whether Huangqi Shengmai Yin (HSY) can inhibit isoprenaline (ISO)-induced myocardial collagen deposition in rats, thereby reducing the cardiac dysfunction caused by MF. The results of echocardiography showed that HSY upregulated fractional shortening and ejection fraction, and reduced the left ventricular systolic dysfunction in the rats with MF. Pathological results showed that HSY protected myocardium, inhibited apoptosis, and effectively reduced collagen deposition. HSY also inhibited the expression of collagen I and III and α-smooth muscle actin (α-SMA) in the heart tissue. HSY increased the expression of Sirtuin 3 (Sirt3) and inhibited the protein levels of the components in the transforming growth factor-β (TGF-β)/Smad pathway. At the same time, it also regulated the expression of related proteins in the matrix metalloproteinases family. In summary, HSY played a therapeutic role in rats with ISO-induced MF by protecting myocardium and inhibiting collagen deposition. Therefore, HSY is a potential therapeutic agent for ameliorating MF.

The editors are publishing this note to alert readers to a concern about [this article][1] ([1][2]). Four sets of identical representative images exist: Fig. 4B Hec-1A/Control and Fig. 4B Hec-1A SD+PDGF-AA+HmIgG; Fig. 5B CD31/3G3 and Supplementary Fig. S2 CD31/Paclitaxel; Fig. 5B TUNEL/PBS and