Displaying publications 1 - 20 of 25 in total

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  1. Cao Y, Chen L, Chen H, Cun Y, Dai X, Du H, et al.
    Natl Sci Rev, 2023 Apr;10(4):nwac287.
    PMID: 37089192 DOI: 10.1093/nsr/nwac287
  2. Devereaux PJ, Lamy A, Chan MTV, Allard RV, Lomivorotov VV, Landoni G, et al.
    N Engl J Med, 2022 Mar 03;386(9):827-836.
    PMID: 35235725 DOI: 10.1056/NEJMoa2000803
    BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations.

    METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex).

    RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit.

    CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

  3. Xiao L, Parolia A, Qiao Y, Bawa P, Eyunni S, Mannan R, et al.
    Nature, 2022 Jan;601(7893):434-439.
    PMID: 34937944 DOI: 10.1038/s41586-021-04246-z
    The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling1 and is altered in over 20% of cancers2,3. Here we developed a proteolysis-targeting chimera (PROTAC) degrader of the SWI/SNF ATPase subunits, SMARCA2 and SMARCA4, called AU-15330. Androgen receptor (AR)+ forkhead box A1 (FOXA1)+ prostate cancer cells are exquisitely sensitive to dual SMARCA2 and SMARCA4 degradation relative to normal and other cancer cell lines. SWI/SNF ATPase degradation rapidly compacts cis-regulatory elements bound by transcription factors that drive prostate cancer cell proliferation, namely AR, FOXA1, ERG and MYC, which dislodges them from chromatin, disables their core enhancer circuitry, and abolishes the downstream oncogenic gene programs. SWI/SNF ATPase degradation also disrupts super-enhancer and promoter looping interactions that wire supra-physiologic expression of the AR, FOXA1 and MYC oncogenes themselves. AU-15330 induces potent inhibition of tumour growth in xenograft models of prostate cancer and synergizes with the AR antagonist enzalutamide, even inducing disease remission in castration-resistant prostate cancer (CRPC) models without toxicity. Thus, impeding SWI/SNF-mediated enhancer accessibility represents a promising therapeutic approach for enhancer-addicted cancers.
  4. Nakamoto H, Yu XQ, Kim S, Origasa H, Zheng H, Chen J, et al.
    Ther Apher Dial, 2020 Feb;24(1):42-55.
    PMID: 31119846 DOI: 10.1111/1744-9987.12840
    TRK-100STP, a sustained-release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK-100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI2 Derivative for Evaluating Improvement of Renal Function) was a randomized, double-blind, placebo-controlled study conducted at 160 sites in seven Asia-Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK-100STP 120, 240 μg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end-stage renal disease. No significant differences were observed in composite endpoints between TRK-100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK-100STP 120 and 240 μg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms.
  5. Qian M, Zhang H, Kham SK, Liu S, Jiang C, Zhao X, et al.
    Genome Res, 2017 02;27(2):185-195.
    PMID: 27903646 DOI: 10.1101/gr.209163.116
    Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole-transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54.1% of patients (n = 125), 31 of which have not been reported previously. In particular, we described a distinct ALL subtype with a characteristic gene expression signature predominantly driven by chromosomal rearrangements of the ZNF384 gene with histone acetyltransferases EP300 and CREBBP ZNF384-rearranged ALL showed significant up-regulation of CLCF1 and BTLA expression, and ZNF384 fusion proteins consistently showed higher activity to promote transcription of these target genes relative to wild-type ZNF384 in vitro. Ectopic expression of EP300-ZNF384 and CREBBP-ZNF384 fusion altered differentiation of mouse hematopoietic stem and progenitor cells and also potentiated oncogenic transformation in vitro. EP300- and CREBBP-ZNF384 fusions resulted in loss of histone lysine acetyltransferase activity in a dominant-negative fashion, with concomitant global reduction of histone acetylation and increased sensitivity of leukemia cells to histone deacetylase inhibitors. In conclusion, our results indicate that gene fusion is a common class of genomic abnormalities in childhood ALL and that recurrent translocations involving EP300 and CREBBP may cause epigenetic deregulation with potential for therapeutic targeting.
  6. Gao Q, Zhu J, Zhao W, Huang Y, An R, Zheng H, et al.
    Clin Cancer Res, 2022 Jun 01;28(11):2278-2285.
    PMID: 35131903 DOI: 10.1158/1078-0432.CCR-21-3023
    PURPOSE: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer.

    PATIENTS AND METHODS: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453).

    RESULTS: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs.

    CONCLUSIONS: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201.

  7. Zheng H, Qin J, Chen H, Hu H, Zhang X, Yang C, et al.
    Microb Genom, 2021 11;7(11).
    PMID: 34762026 DOI: 10.1099/mgen.0.000659
    Burkholderia pseudomallei is a Gram-negative soil-dwelling bacillus that causes melioidosis, a frequently fatal infectious disease, in tropical and subtropical regions. Previous studies have identified the overall genetic and evolutionary characteristics of B. pseudomallei on a global scale, including its origin and transmission routes. However, beyond its known hyperendemicity foci in northern Australia and Southeast Asia, the distribution and genetic characteristics of B. pseudomallei in most tropical regions remain poorly understood, including in southern China. Here, we sequenced the genomes of 122 B. pseudomallei strains collected from Hainan, an island in southern China, in 2002-2018, to investigate the population structure, relationships with global strains, local epidemiology, and virulence and antimicrobial-resistance factors. A phylogenetic analysis and hierarchical clustering divided the Hainan strains into nine phylogenic groups (PGs), 80 % of which were concentrated within five major groups (group 1: corresponding to minor sequence types [STs], 12.3 %; group 3: ST46 and ST50, 31.1 %; group 9: ST58, 13.1 %; group 11: ST55, 8.2 %; group 15: mainly ST658, 15.6%). A phylogenetic analysis that included global strains suggested that B. pseudomallei in Hainan originated from Southeast Asian countries, transmitted in multiple historical importation events. We also identified several mutual transmission events between Hainan and Southeast Asian countries in recent years, including three importation events from Thailand and Singapore to Hainan and three exportation events from Hainan to Singapore, Malaysia, and Taiwan island. A statistical analysis of the temporal distribution showed that the Hainan strains of groups 3, 9, and 15 have dominated the disease epidemic locally in the last 5 years. The spatial distribution of the Hainan strains demonstrated that some PGs are distributed in different cities on Hainan island, and by combining phylogenic and geographic distribution information, we detected 21 between-city transmission events, indicating its frequent local transmission. The detection of virulence factor genes showed that 56 % of the Hainan strains in group 1 encode a B. pseudomallei-specific adherence factor, boaB, confirming the specific pathogenic characteristics of the Hainan strains in group 1. An analysis of the antimicrobial-resistance potential of B. pseudomallei showed that various kinds of alterations were identified in clinically relevant antibiotic resistance factors, such as AmrR, PenA and PBP3, etc. Our results clarify the population structure, local epidemiology, and pathogenic characteristics of B. pseudomallei in Hainan, providing further insight into its regional and global transmission networks and improving our knowledge of its global phylogeography.
  8. Xu X, Shen Y, Zhang Y, Li Q, Wang W, Chen L, et al.
    Front Plant Sci, 2022;13:1075353.
    PMID: 36684775 DOI: 10.3389/fpls.2022.1075353
    In 2003, Kandelia obovata was identified as a new mangrove species differentiated from Kandelia candel. However, little is known about their chloroplast (cp) genome differences and their possible ecological significance. In this study, 25 whole cp genomes, with seven samples of K. candel from Malaysia, Thailand, and Bangladesh and 18 samples of K. obovata from China, were sequenced for comparison. The cp genomes of both species encoded 128 genes, namely 83 protein-coding genes, 37 tRNA genes, and eight rRNA genes, but the cp genome size of K. obovata was ~2 kb larger than that of K. candle due to the presence of more and longer repeat sequences. Of these, tandem repeats and simple sequence repeats exhibited great differences. Principal component analysis based on indels, and phylogenetic tree analyses constructed with homologous protein genes from the single-copy genes, as well as 38 homologous pair genes among 13 mangrove species, gave strong support to the separation of the two species within the Kandelia genus. Homologous genes ndhD and atpA showed intraspecific consistency and interspecific differences. Molecular dynamics simulations of their corresponding proteins, NAD(P)H dehydrogenase chain 4 (NDH-D) and ATP synthase subunit alpha (ATP-A), predicted them to be significantly different in the functions of photosynthetic electron transport and ATP generation in the two species. These results suggest that the energy requirement was a pivotal factor in their adaptation to differential environments geographically separated by the South China Sea. Our results also provide clues for future research on their physiological and molecular adaptation mechanisms to light and temperature.
  9. Shi X, Waiho K, Li X, Ikhwanuddin M, Miao G, Lin F, et al.
    BMC Genomics, 2018 Dec 29;19(1):981.
    PMID: 30594128 DOI: 10.1186/s12864-018-5380-8
    BACKGROUND: Mud crabs, Scylla spp., are commercially important large-size marine crustaceans in the Indo-West Pacific region. As females have the higher growth rate and economic value, the production of all female stocks is extremely essential in aquaculture. However, the sex determination mechanism is still unclear. Development of sex-specific genetic markers based on next-generation sequencing proved to be an effective tool for discovering sex determination system in various animals.

    RESULTS: Restriction-site associated DNA sequencing (RAD-seq) was employed to isolate sex-specific SNP markers for S. paramamosain. A total of 335.6 million raw reads were obtained from 20 individuals, of which 204.7 million were from 10 females and 130.9 million from 10 males. After sequence assembly and female-male comparison, 20 SNP markers were identified to be sex-specific. Furthermore, ten SNPs in a short sequence (285 bp) were confirmed heterozygous in females and homozygous in males in a large population by PCR amplification and sequencing. Subsequently, a female-specific primer was successfully designed according to the female-specific nucleotide which could amplify an expected band from females but not from males. Thus, a rapid and effective method for molecular sexing in S. paramamosain was developed, meanwhile, this method could successfully identify the sex of S. tranquebarica and S. serrata. Finally, nine and four female-specific SNP markers were detected in S. tranquebarica and S. serrata, respectively.

    CONCLUSIONS: Sex-specific SNP markers were firstly identified in crab species and showed female heterogamety and male homogamety, which provided strong genetic evidence for a WZ/ZZ sex determination system in mud crabs S. paramamosain, S. tranquebarica and S. serrata. These findings will lay a solid foundation for the study of sex determination mechanism, sex chromosome evolution, and the development of mono-sex population in crustaceans.

  10. Fang S, Zhang Y, Shi X, Zheng H, Li S, Zhang Y, et al.
    Genomics, 2020 01;112(1):404-411.
    PMID: 30851358 DOI: 10.1016/j.ygeno.2019.03.003
    In this study, we first identified male-specific SNP markers using restriction site-associated DNA sequencing, and further developed a PCR-based sex identification technique for Charybdis feriatus. A total of 296.96 million clean reads were obtained, with 114.95 and 182.01 million from females and males. After assembly and alignment, 10 SNP markers were identified being heterozygous in males but homozygous in females. Five markers were further confirmed to be male-specific in a large number of individuals. Moreover, two male-specific sense primers and a common antisense primer were designed, using which, a PCR-based genetic sex identification method was successfully developed and used to identify the sex of 103 individuals, with a result of 49 females and 54 males. The presence of male-specific SNP markers suggests an XX/XY sex determination system for C. feriatus. These findings should be helpful for better understanding sex determination mechanism, and drafting artificial breeding program in crustaceans.
  11. Waiho K, Shi X, Fazhan H, Li S, Zhang Y, Zheng H, et al.
    Front Genet, 2019;10:298.
    PMID: 31024620 DOI: 10.3389/fgene.2019.00298
    Mud crab, Scylla paramamosain is one of the most important crustacean species in global aquaculture. To determine the genetic basis of sex and growth-related traits in S. paramamosain, a high-density genetic linkage map with 16,701 single nucleotide polymorphisms (SNPs) was constructed using SLAF-seq and a full-sib family. The consensus map has 49 linkage groups, spanning 5,996.66 cM with an average marker-interval of 0.81 cM. A total of 516 SNP markers, including 8 female-specific SNPs segregated in two quantitative trait loci (QTLs) for phenotypic sex were located on LG32. The presence of female-specific SNP markers only on female linkage map, their segregation patterns and lower female: male recombination rate strongly suggest the conformation of a ZW/ZZ sex determination system in S. paramamosain. The QTLs of most (90%) growth-related traits were found within a small interval (25.18-33.74 cM) on LG46, highlighting the potential involvement of LG46 in growth. Four markers on LG46 were significantly associated with 10-16 growth-related traits. BW was only associated with marker 3846. Based on the annotation of transcriptome data, 11 and 2 candidate genes were identified within the QTL regions of sex and growth-related traits, respectively. The newly constructed high-density genetic linkage map with sex-specific SNPs, and the identified QTLs of sex- and growth-related traits serve as a valuable genetic resource and solid foundation for marker-assisted selection and genetic improvement of crustaceans.
  12. Cui W, Fang S, Lv L, Huang Z, Lin F, Wu Q, et al.
    Front Vet Sci, 2021;8:712942.
    PMID: 34395579 DOI: 10.3389/fvets.2021.712942
    In order to uncover the sexual difference in morphology and how early they appear during the development stage of mud crab Scylla paramamosain, we measured, observed, and biostatistically analyzed morphological traits related to sex. For unveiling the morphological differences between sexes, morphological traits involving abdomen width (AW), carapace length (CL), and carapace width (CW) were first measured during the crablet development stage of S. paramamosain in the present study. The correlation analyses and path analyses exhibited that sexual dimorphism in the third abdomen width (AW3) and fourth abdomen width (AW4) could be used for sex identification from stage C VI (stage VI of crablet). Based on the stepwise discriminant analysis and standardized traits, a sex discriminant equation was constructed, which is capable for sex identification in crablets from stage C VI. Observations for secondary sexual traits and abdomen morphology (shape and pleopods) using a dissecting microscope or scanning electron microscope indicated that sexes are easily identified at stage C VIII according to the abdomen shape; meanwhile, at stage C II based on pleopod difference, and at stage C I by the presence or absence of gonopores. The findings in this study contribute greatly to the accuracy of sex identification of S. paramamosain during the early development stage, which promotes the understanding of the morphological differentiation mechanism of sex.
  13. Zheng H, Badenhorst CE, Lei TH, Liao YH, Che Muhamed AM, Fujii N, et al.
    Am J Physiol Regul Integr Comp Physiol, 2021 06 01;320(6):R780-R790.
    PMID: 33787332 DOI: 10.1152/ajpregu.00014.2021
    The current study investigated whether ambient heat augments the inflammatory and postexercise hepcidin response in women and if menstrual phase and/or self-pacing modulate these physiological effects. Eight trained females (age: 37 ± 7 yr; V̇o2max: 46 ± 7 mL·kg-1·min-1; peak power output: 4.5 ± 0.8 W·kg-1) underwent 20 min of fixed-intensity cycling (100 W and 125 W) followed by a 30-min work trial (∼75% V̇o2max) in a moderate (MOD: 20 ± 1°C, 53 ± 8% relative humidity) and warm-humid (WARM: 32 ± 0°C, 75 ± 3% relative humidity) environment in both their early follicular (days 5 ± 2) and midluteal (days 21 ± 3) phases. Mean power output was 5 ± 4 W higher in MOD than in WARM (P = 0.02) such that the difference in core temperature rise was limited between environments (-0.29 ± 0.18°C in MOD, P < 0.01). IL-6 and hepcidin both increased postexercise (198% and 38%, respectively); however, neither was affected by ambient temperature or menstrual phase (all P > 0.15). Multiple regression analysis demonstrated that the IL-6 response to exercise was explained by leukocyte and platelet count (r2 = 0.72, P < 0.01), and the hepcidin response to exercise was explained by serum iron and ferritin (r2 = 0.62, P < 0.01). During exercise, participants almost matched their fluid loss (0.48 ± 0.18 kg·h-1) with water intake (0.35 ± 0.15 L·h-1) such that changes in body mass (-0.3 ± 0.3%) and serum osmolality (0.5 ± 2.0 osmol·kgH2O-1) were minimal or negligible, indicating a behavioral fluid-regulatory response. These results indicate that trained, iron-sufficient women suffer no detriment to their iron regulation in response to exercise with acute ambient heat stress or between menstrual phases on account of a performance-physiological trade-off.
  14. Lei TH, Schlader ZJ, Che Muhamed AM, Zheng H, Stannard SR, Kondo N, et al.
    Eur J Appl Physiol, 2020 Apr;120(4):841-852.
    PMID: 32072226 DOI: 10.1007/s00421-020-04322-8
    PURPOSE: Recent studies have determined that ambient humidity plays a more important role in aerobic performance than dry-bulb temperature does in warm environments; however, no studies have kept humidity constant and independently manipulated temperature. Therefore, the purpose of this study was to determine the contribution of dry-bulb temperature, when vapor pressure was matched, on the thermoregulatory, perceptual and performance responses to a 30-min cycling work trial.

    METHODS: Fourteen trained male cyclists (age: 32 ± 12 year; height: 178 ± 6 cm; mass: 76 ± 9 kg; [Formula: see text]: 59 ± 9 mL kg-1 min-1; body surface area: 1.93 ± 0.12 m2; peak power output: 393 ± 53 W) volunteered, and underwent 1 exercise bout in moderate heat (MOD: 34.9 ± 0.2 °C, 50.1 ± 1.1% relative humidity) and 1 in mild heat (MILD: 29.2 ± 0.2 °C, 69.4 ± 0.9% relative humidity) matched for vapor pressure (2.8 ± 0.1 kPa), with trials counterbalanced.

    RESULTS: Despite a higher weighted mean skin temperature during MOD (36.3 ± 0.5 vs. 34.5 ± 0.6 °C, p 

  15. Zheng H, Badenhorst CE, Lei TH, Che Muhamed AM, Liao YH, Amano T, et al.
    J Appl Physiol (1985), 2021 11 01;131(5):1496-1504.
    PMID: 34590913 DOI: 10.1152/japplphysiol.00342.2021
    Measurement error(s) of exercise tests for women are severely lacking in the literature. The purpose of this investigation was to 1) determine whether ovulatory status or ambient environment were moderating variables when completing a 30-min self-paced work trial and 2) provide test-retest norms specific to athletic women. A retrospective analysis of three heat stress studies was completed using 33 female participants (31 ± 9 yr, 54 ± 10 mL·min-1·kg-1) that yielded 130 separate trials. Participants were classified as ovulatory (n = 19), anovulatory (n = 4), and oral contraceptive pill users (n = 10). Participants completed trials ∼2 wk apart in their (quasi-) early follicular and midluteal phases in two of moderate (1.3 ± 0.1 kPa, 20.5 ± 0.5°C, 18 trials), warm-dry (2.2 ± 0.2 kPa, 34.1 ± 0.2°C, 46 trials), or warm-humid (3.4 ± 0.1 kPa, 30.2 ± 1.1°C, 66 trials) environments. We quantified reliability using limits of agreement, intraclass correlation coefficient (ICC), standard error of measurement (SEM), and coefficient of variation (CV). Test-retest reliability was high, clinically valid (ICC = 0.90, P < 0.01), and acceptable with a mean CV of 4.7%, SEM of 3.8 kJ (2.1 W), and reliable bias of -2.1 kJ (-1.2 W). The various ovulatory status and contrasting ambient conditions had no appreciable effect on reliability. These results indicate that athletic women can perform 30-min self-paced work trials ∼2 wk apart with an acceptable and low variability irrespective of their hormonal status or heat-stressful environments.NEW & NOTEWORTHY This study highlights that aerobically trained women perform 30-min self-paced work trials ∼2 wk apart with acceptably low variability and their hormonal/ovulatory status and the introduction of greater ambient heat and humidity do not moderate this measurement error.
  16. Bain O, Chandrasekharan SA, Partono F, Mak JW, Zheng HJ, Seo BS, et al.
    Ann Parasitol Hum Comp, 1988;63(3):209-23.
    PMID: 3190122
    A comparative study of five periodic human strains of Brugia malayi, originating from India, China, Korea, Malaysia and Indonesia, is given. This morphological analysis is based on males; the "standard" characters (oesophagus, papillae, spicules...) appear identical. On the contrary, the cuticular ornamentation of the posterior region--which is composed of the area rugosa and of a system of bosses and constitutes a secondary non-skid copulatory apparatus--differs following the geographical origin of the strain. A key is given, based on this character. 1(2) At 800-1,200 micron from the tip of tail, numerous cuticular bosses present on the right side of the body (fig. 2 and 8 B). 2(1) At 800-1,200 micron from the tip of tail, cuticular bosses absent or scarce on the right side of the body (fig. 8 D). 3(4) At 1,800-1,200 micron from the tip of tail (fig. 4), scarce and slightly projecting cuticular bosses on the dorsal side of the body contrasting with well projecting lateral cuticular bosses (fig. 9 E and F). Anterior extremity of the area rugosa made by a few stripes of tiny bosses linked transversally (fig. 9 A). 4(3) At 1,800-2,200 micron, numerous cuticular bosses on the dorsal side of the body (figs. 5, 6 and 7). Anterior extremity of the area rugosa made by the stripes of longitudinal rods (fig. 9C). 5(6) Oblong transversally stretched cuticular bosses on the dorsal and left sides of the body, anteriorly to the area rugosa (fig. 5); big oblong bosses on the left side (fig. 9 B). Transversal wrinkles and stripes of rods absent on the dorsal side of the body. 6(5) Round cuticular bosses on the dorsal and left sides of the body anteriorly to the area rugosa (figs. 6 and 7): no big oblong bosses on the left side. Transversal wrinkles or stripes of rods present on the dorsal side of the body (fig. 9 D). Nomenclaturally, such differences could be used in defining different taxa, but it could be useful to perform "blind determination" (material without labelling), to study conveniently the morphology of microfilariae (often an excellent indication for speciation in that group of Nematodes) and, evenly, to proceed to parallel studies on isoenzymes. However, whatever could be the taxonomical conclusion, the differences observed in Brugia malayi originating from different regions appear to the sufficient to consider the existence of four distinct diseases.
  17. Waiho K, Fazhan H, Zhang Y, Zhang Y, Li S, Zheng H, et al.
    Mar Biotechnol (NY), 2019 Jun;21(3):320-334.
    PMID: 30835008 DOI: 10.1007/s10126-019-09882-1
    Although the sexual dimorphism in terms of gonadal development and gametogenesis of mud crab has been described, the internal regulating mechanism and sex differentiation process remain unclear. A comparative gonadal miRNA transcriptomic study was conducted to identify miRNAs that are differentially expressed between testes and ovaries, and potentially uncover miRNAs that might be involved in sex differentiation and gonadal maturation mechanisms of mud crabs (Scylla paramamosain). A total of 10 known miRNAs and 130 novel miRNAs were identified, among which 54 were differentially expressed. Target gene prediction revealed a significant enrichment in 30 KEGG pathways, including some reproduction-related pathways, e.g. phosphatidylinositol signalling system and inositol phosphate metabolism pathways. Further analysis on six differentially expressed known miRNAs, six differentially expressed novel miRNAs and their reproduction-related putative target genes shows that both miRNAs and putative target genes showed stage-specific expression during gonadal maturation, suggesting their potential regulatory roles in sex differentiation and reproductive development. This study reveals the sex-biased miRNA profile and establishes a solid foundation for understanding the sex differentiation and gonadal maturation mechanisms of S. paramamosain.
  18. Zhang Y, Wu Q, Fang S, Li S, Zheng H, Zhang Y, et al.
    BMC Genomics, 2020 Aug 14;21(1):559.
    PMID: 32795331 DOI: 10.1186/s12864-020-06965-5
    BACKGROUND: Mud crab, Scylla paramamosain, a euryhaline crustacean species, mainly inhabits the Indo-Western Pacific region. Wild mud crab spawn in high-salt condition and the salinity reduced with the growth of the hatching larvae. When the larvae grow up to megalopa, they migrate back to estuaries and coasts in virtue of the flood tide, settle and recruit adult habitats and metamorphose into the crablet stage. Adult crab can even survive in a wide salinity of 0-35 ppt. To investigate the mRNA profile after salinity stress, S. paramamosain megalopa were exposed to different salinity seawater (low, 14 ppt; control, 25 ppt; high, 39 ppt).

    RESULTS: Firstly, from the expression profiles of Na+/K+/2Cl- cotransporter, chloride channel protein 2, and ABC transporter, it turned out that the 24 h might be the most influenced duration in the short-term stress. We collected megalopa under different salinity for 24 h and then submitted to mRNA profiling. Totally, 57.87 Gb Clean Data were obtained. The comparative genomic analysis detected 342 differentially expressed genes (DEGs). The most significantly DEGs include gamma-butyrobetaine dioxygenase-like, facilitated trehalose transporter Tret1, sodium/potassium-transporting ATPase subunit alpha, rhodanese 1-like protein, etc. And the significantly enriched pathways were lysine degradation, choline metabolism in cancer, phospholipase D signaling pathway, Fc gamma R-mediated phagocytosis, and sphingolipid signaling pathway. The results indicate that in the short-term salinity stress, the megalopa might regulate some mechanism such as metabolism, immunity responses, osmoregulation to adapt to the alteration of the environment.

    CONCLUSIONS: This study represents the first genome-wide transcriptome analysis of S. paramamosain megalopa for studying its stress adaption mechanisms under different salinity. The results reveal numbers of genes modified by salinity stress and some important pathways, which will provide valuable resources for discovering the molecular basis of salinity stress adaptation of S. paramamosain larvae and further boost the understanding of the potential molecular mechanisms of salinity stress adaptation for crustacean species.

  19. Tan K, Zhang H, Lim LS, Ma H, Li S, Zheng H
    Front Immunol, 2019;10:3041.
    PMID: 32010132 DOI: 10.3389/fimmu.2019.03041
    Carotenoids are biologically active pigments that are well-known to enhance the defense and immunity of the vertebrate system. However, in invertebrates, the role of carotenoids in immunity is not clear. Therefore, this study aims to review the scientific evidence for the role of carotenoids in invertebrate immunization. From the analysis of published literatures and recent studies from our laboratory, it is obvious that carotenoids are involved in invertebrate immunity in two ways. On the one hand, carotenoids can act as antioxidant enzymes to remove singlet oxygen, superoxide anion radicals, and hydroxyl radicals, thereby reducing SOD activity and reducing the cost of immunity. In some organisms, carotenoids have been shown to promote SOD activity by up-regulating the expression of the ZnCuSOD gene. Carotenoids, on the other hand, play a role in the expression and regulation of many genes involved in invertebrate immunity, including thioredoxins (TRX), peptidoglycan recognition receptor proteins (PGRPs), ferritins, prophenoloxidase (ProPO), vitellogenin (Vg), toll-like receptor (TLRs), heat shock proteins (HSPs), and CuZnSOD gene. The information in this review is very useful for updating our understanding of the progress of carotenoid research in invertebrate immunology and to help identify topics for future topics.
  20. Waiho K, Fazhan H, Zhang Y, Li S, Zhang Y, Zheng H, et al.
    Genomics, 2020 01;112(1):323-331.
    PMID: 30807818 DOI: 10.1016/j.ygeno.2019.02.012
    PIWI-interacting RNAs (piRNAs) are abundantly found in germ cells and involved in gametogenesis and gonadal development. Information on the regulatory roles of piRNAs in crustacean reproduction, however, is scarce. Thus, we identified gonadal piRNAs of mud crab Scylla paramamosain. Of the 115,491 novel piRNAs, 596 were differentially expressed. Subsequently, 389,887 potential piRNA-target genes were predicted. The expression of 4 piRNAs and 9 genes with high piRNA interactions were validated with the inclusion of additional immature specimens, including LRP2 that is involved in growth and reproduction, MDN1 in ribosome biogenesis pathway and gametogenesis, and PRKDC, a DNA repair gene involved in gonadal differentiation and maturation. KEGG analysis further revealed the involvement of predicted piRNA target genes in gametogenesis- and reproduction-related pathways. Our findings provide baseline information of mud crab piRNAs and their differential expression between testes and ovaries suggests that piRNAs play an essential role in regulating gametogenesis and gonadal development.
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