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Biomedical subjects

Bing Wang

Publications and source records attributed to Bing Wang.

At least 19 recordsLinked to original sources

Strigolactones constrain rice drought acclimation by suppressing ROS scavenging through the D53-OsWRKY31-ZFP36 module.

Strigolactones (SLs) are a class of plant hormones essential for tiller development and yield under diverse environmental conditions. Drought is a major limiting factor for rice yields. Although SLs contribute to drought resistance, mechanisms and practical applications of SL pathway in drought acclimation of rice remain poorly understood. Our study shows that short-term dehydration represses SL biosynthesis in rice roots. Genetic assays indicate that disruption of SL biosynthesis or signaling elevates rice drought resistance, whereas SL signaling activation or supplementation with the SL analog GR244DO impairs drought resistance. SLs negatively regulate drought acclimation by promoting degradation of the repressor protein DWARF53 (D53). D53 interacts with the transcription factor OsWRKY31 via its N-terminal domain and suppresses the protein level of OsWRKY31, which binds to and represses transcription of the ZFP36 promoter. ZFP36 encodes a zinc-finger transcription factor that promotes H2O2 scavenging to sustain reactive oxygen species (ROS) homeostasis during drought stress. Notably, the drought-resistant upland rice variety IRAT109 exhibits lower SL levels in root exudates than the lowland rice variety Nipponbare (NP). Genome editing of key components in SL pathway enhances drought resistance in NP, Huazhan (HZ), and IRAT109. The agronomic potential of tuning SL biosynthesis is further supported by the elite D17/HTD1 allele, which weakens SL biosynthesis and improves drought resistance and grain yield in Nekken 2 (NK2) under field conditions. These findings uncover a key mechanism underlying SL-repressed drought acclimation in rice and provide an effective strategy to improve drought resistance in diverse rice varieties amid ongoing climate change.

D53↗

Structural basis of sex pheromone detection in aphids.

Sex pheromones play a central role in regulating animal behavior and reproduction. In insects, these signals are perceived through specialized odorant receptors (ORs) that mediate species-specific communication and safeguard genetic integrity. However, the structural basis of sex pheromone detection remains largely unresolved. Here, we identified two ORs in the pea aphid Acyrthosiphon pisum, along with the conserved OR co-receptor (Orco), which together mediate recognition of the pheromone components nepetalactone and nepetalactol. Functional assays demonstrated that ApOR21-Orco and ApOR22-Orco specifically respond to nepetalactol and nepetalactone, respectively. Using cryo-electron microscopy, we resolved the structure of the ApOR22-Orco complex in three states - unbound closed, nepetalactone-bound closed, and nepetalactone-bound open - revealing a heterotetrameric ion channel formed by one ApOR22 and three ApOrco subunits. Ligand binding to ApOR22 triggers conformational rearrangements that induce asymmetric pore dilation, thereby enabling ion conduction. Together, these results provide a mechanistic framework for understanding sex pheromone perception in insects and establish a structural foundation for the rational development of environmentally sustainable pest-control strategies.

Animals↗

Selective targeting of a histone-like silencer Sfx to the R6K conjugal transfer operon.

Conjugative plasmids drive bacterial evolution and antibiotic resistance spread, yet their gene expression must be silenced to protect the host. A histone-like protein H-NS represses many mobile and sedentary xenogenes but fails to silence the conjugal transfer vir operon of R6K, a prototype IncX plasmid. Instead, R6K encodes its own H-NS homolog, Sfx, to repress the vir operon. Here, we show that, unlike other plasmid silencers that target promoters, Sfx cooperates with Rho factor to arrest transcription elongation. ChIP-seq reveals that Sfx and H-NS share similar DNA motifs and a preference for negative supercoiling, but occupy reciprocal genomic niches; Sfx is enriched on the R6K vir operon despite weak chromosomal binding, whereas H-NS displays the opposite preference. We show that Sfx binding to vir DNA critically depends on DNA topology and hypothesize that its selective targeting to R6K is mediated by Sfx-vir interactions and phase separation. Our results suggest that Sfx phase separates with R6K to ensure its preferential recruitment to the plasmid DNA and forms stable bridged nucleoprotein filaments that are impermeable to competitors such as H-NS. These findings reveal how histone-like proteins can partition the genome into distinct regulatory niches, a strategy likely mirrored across all life.

Operon↗

Label-free structural imaging of plant roots and microbes using third-harmonic generation microscopy.

Root biology is pivotal in addressing global challenges including sustainable agriculture and climate change. However, roots have been relatively understudied among plant organs, partly due to the difficulties in imaging root structures in their natural environment. Here we used microfabricated ecosystems (EcoFABs) to establish growing environments with optical access and employed nonlinear multimodal microscopy of third-harmonic generation (THG) and three-photon fluorescence (3PF) to achieve label-free, in situ imaging of live roots and microbes at high spatiotemporal resolution. THG enabled us to observe key plant root structures including the vasculature, Casparian strips, dividing meristematic cells, and root cap cells, as well as subcellular features including nuclear envelopes, nucleoli, starch granules, and putative stress granules. THG from the cell walls of bacteria and fungi also provides label-free contrast for visualizing these microbes in the root rhizosphere. With simultaneously recorded 3PF signal, we demonstrated our ability to investigate root-microbe interactions by achieving single-bacterium tracking and subcellular imaging of fungal spores and hyphae in the rhizosphere.

Plant Roots↗

FTDC1/2, oocyte-specific cofactors of DNMT1 required for epigenetic regulation and embryonic development.

The unique epigenetic patterns during gametogenesis and embryonic development indicate the existence of specialized methylation machinery. In the present study, we describe the discovery of two oocyte-specific cofactors of DNA methyltransferase 1 (DNMT1), encoded by uncharacterized genes, ferritin domain containing 1 and 2 (Ftdc1 and Ftdc2). Genetic ablation of Ftdc1 or Ftdc2 causes midgestation defects and female infertility. FTDC1 or FTDC2 depletion induces the progressive loss of DNA methylation including imprinted regions in early embryos. This loss correlates with a marked reduction in DNMT1 protein due to increased degradation, likely via the ubiquitin-proteasome pathway. Mechanistically, we find that FTDC1, FTDC2 and DNMT1 form a complex by direct interactions, thereby stabilizing each other. Surprisingly, knockout of Ftdc1 or Ftdc2 displayed stronger DNA demethylation phenotypes and earlier embryonic lethality than the Dnmt1-null mutant, implying their unique functions. These data suggest that FTDC1/2 are crucial players specifically involved in maintaining genomic methylation during embryogenesis, offering new insights into the epigenetic control of mammalian development.

DNA (Cytosine-5-)-Methyltransferase 1↗

Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.

Efficient and widespread gene transfer is required for successful treatment of Duchenne muscular dystrophy (DMD). Here, we performed the first clinical trial using a chimeric adeno-associated virus (AAV) capsid variant (designated AAV2.5) derived from a rational design strategy. AAV2.5 was generated from the AAV2 capsid with five mutations from AAV1. The novel chimeric vector combines the improved muscle transduction capacity of AAV1 with reduced antigenic crossreactivity against both parental serotypes, while keeping the AAV2 receptor binding. In a randomized double-blind placebo-controlled phase I clinical study in DMD boys, AAV2.5 vector was injected into the bicep muscle in one arm, with saline control in the contralateral arm. A subset of patients received AAV empty capsid instead of saline in an effort to distinguish an immune response to vector versus minidystrophin transgene. Recombinant AAV genomes were detected in all patients with up to 2.56 vector copies per diploid genome. There was no cellular immune response to AAV2.5 capsid. This trial established that rationally designed AAV2.5 vector was safe and well tolerated, lays the foundation of customizing AAV vectors that best suit the clinical objective (e.g., limb infusion gene delivery) and should usher in the next generation of viral delivery systems for human gene transfer.

Amino Acid Sequence↗

Evaluation of potential gene-gene interactions for attention deficit hyperactivity disorder in the Han Chinese population.

Several lines of evidence suggest that attention-deficit/hyperactivity disorder (ADHD) is a polygenic disorder produced by the interaction of several genes with minor effects. To explore potential gene-gene interactions among candidate genes for ADHD, we studied the dopamine D2 receptor (DRD2), dopamine D4 receptor (DRD4), dopamine transporter (DAT1), and catechol-O-methyltransferase (COMT) genes in the Han Chinese population. A sample of 340 children with ADHD was diagnosed according to the DSM-IV criteria. We also recruited 226 unrelated controls. Identified polymorphisms included a 48-base-pair-repeat in Exon 3 of DRD4, a 40-base-pair-repeat in the 3' untranslated region of DAT1, a restriction-fragment-length polymorphism at codon 158 of COMT, and a -241A > G transition in the promoter of DRD2. Associations of polymorphisms with ADHD and its subtypes were examined by comparing allele frequencies between probands and controls. Binary logistic regression analysis was used to examine the potential gene-gene interactions. Binary logistic regression analysis with the sample of refined phenotypes showed that male gender and long-repeat genotypes of DRD4 and DAT1 were independent risk factors for ADHD. We found no evidence for gene-gene interactions among the candidate genes studied. The present study suggests that dopamine candidate genes are associated with increased vulnerability to ADHD in the Han Chinese population.

Adolescent↗

Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects.

Prior work has shown reduced serotonin transmission to be associated with impulsivity and behavioral problems. The current study assessed the association between ADHD and two variants of the serotonin transporter gene: the 44-bp deletion/insertion polymorphism (5-HTTLPR) and the 17 bp-repeat polymorphism in intron 2 (STin2.VNTR). We hypothesized that ADHD phenotypes associated with impulsivity would show an association with these variants. Two-hundred and ninety-three ADHD trios were genotyped and analyzed using transmission disequilibrium test (TDT) analysis and haplotype analysis. We found no association between the STin2.VNTR and ADHD, but did find preferential transmission of the S allele of the 5-HTTLPR polymorphism (chi(2) = 5.751, P = 0.016) to probands with ADHD. Haplotype analysis found the L/10 haplotype was over-transmitted (chi(2) = 6.172, P = 0.013), while L/12 was under-transmitted to probands with ADHD (chi(2) = 4.866, P = 0.027).

Alleles↗

Molecular cloning, characterization and expression analysis of a putative C-type lectin (Fclectin) gene in Chinese shrimp Fenneropenaeus chinensis.

Lectin is regarded as a potential molecule involved in immune recognition and phagocytosis through opsonization in crustacean. Knowledge on lectin at molecular level would help us to understand its regulation mechanism in crustacean immune system. A novel C-type lectin gene (Fclectin) was cloned from hemocytes of Chinese shrimp Fenneropenaeus chinensis by 3' and 5' rapid amplification of cDNA ends (RACE) PCR. The full-length cDNA consists of 1482 bp with an 861 bp open reading frame, encoding 287 amino acids. The deduced amino acid sequence contains a putative signal peptide of 19 amino acids. It also contains two carbohydrate recognition domains/C-type lectin-like domains (CRD1 and CRD2), which share 78% identity with each other. CRD1 and CRD2 showed 34% and 30% identity with that of mannose-binding lectin from Japanese lamprey (Lethenteron japonicum), respectively. Both CRD1 and CRD2 of Fclectin have 11 amino acids residues, which are relatively invariant in animals' C-type lectin CRDs. Five residues at Ca2+ binding site 1 are conserved in Fclectin. The potential Ca2+/carbohydrate-binding (site 2) motif QPD, E, NP (Gln-Pro-Asp, Glu, Asn-Pro) presented in the two CRDs of Fclectin may support its ability to bind galactose-type sugars. It could be deduced that Fclectin is a member of C-type lectin superfamily. Transcripts of Fclectin were found only in hemocytes by Northern blotting and RNA in situ hybridization. The variation of mRNA transcription level in hemocytes during artificial infection with bacteria and white spot syndrome virus (WSSV) was quantitated by capillary electrophoresis after RT-PCR. An exploration of mRNA expression variation after LPS stimulation was carried out in primarily cultured hemocytes in vitro. Expression profiles of Fclectin gene were greatly modified after bacteria, LPS or WSSV challenge. The above-stated data can provide us clues to understand the probable role of C-type lectin in innate immunity of shrimp and would be helpful to shrimp disease control.

Amino Acid Sequence↗

Levetiracetam reduces anesthetic-induced hyperalgesia in rats.

BACKGROUND: As part of an increase in excitability, small doses of pentobarbital, propofol, and midazolam induce an increased sensitivity to pain. Specific therapy to prevent or reduce this excitability may offer advantages over current clinical management with analgesics and sedatives. The pharmacological profile of the novel antiepileptic drug, levetiracetam, suggests that it may reduce the intensity of the excitatory stages of anesthesia. METHODS: We examined the influence of levetiracetam on the reduction of the nociceptive reflex threshold in rats by sedative doses of pentobarbital, propofol, and midazolam. Measurements of nociceptive reflex threshold to pressure and heat were made and then repeated after intraperitoneal injection of saline or one of three doses of levetiracetam (100, 200, 500 mg/kg). Pentobarbital (30 mg/kg), propofol (30 mg/kg), or midazolam (1.9 mg/kg) were then administered. The reflex threshold was measured every 10 min, starting at 5 min after the sedative injection, until 65 min had elapsed. RESULTS: Levetiracetam did not alter nociceptive reflex threshold in nonsedated animals (P = 0.11) or influence the degree or duration of sedation. The three anesthetic/sedative drugs reduced the nociceptive reflex threshold by 20%-30% of control values. Levetiracetam reduced the hyperreflexia associated with pentobarbital and midazolam (P < 0.05), but not propofol. CONCLUSIONS: These findings support further investigation into the role of levetiracetam in the prevention of anesthetic-induced excitability.

Anesthesia↗

Metabolic fate of intravenously administered N-acetylneuraminic acid-6-14C in newborn piglets.

BACKGROUND: Sialic acid (N-acetylneuraminic acid), a component of gangliosides and sialylglycoproteins, may be a conditional nutrient in early life because endogenous synthesis is limited. The aim of this study was to investigate the metabolic fate of intravenously administrated N-acetylneuraminic acid-6-14C (sialic acid) in piglets. METHOD: Three-day-old male domestic piglets (Sus scrofa) were injected via the jugular vein with 5 microCi (11-12 x 10(6) cpm) of N-acetylneuraminic acid-6-14C (specific activity of 55 mCi/mmol). Blood samples were collected at regular intervals over the next 120 min. The organs were then removed and the urine collected for determination of residual radioactivity. RESULTS: Within 2 min of injection, 80% of the activity was removed from the blood and by 120 min the remaining activity approached 8%. At 120 min, the brain contained significantly more radioactivity (cpm/g tissue) than the liver, pancreas, heart and spleen, but less than the kidneys. Within the brain, the percentage of total injected activity was highest in the cerebrum (0.175 +/-0.008) followed by the cerebellum (0.0295 +/-0.006, p=0.00006) and the thalamus (0.029 +/- 0.006, p =0.00003). CONCLUSIONS: An exogenous source of sialic acid is capable of crossing the blood-brain barrier and being taken up into various tissues. The findings suggest that dietary sources of sialic acid may contribute to early brain development in newborn mammals.

Animals↗

Application of spiral CT image 3D reconstruction in severe talar neck fracture.

OBJECTIVE: To explore the application of the spiral computerized tomography (CT) image three-dimensional (3D) reconstruction technique associated with the conventional radiography in the diagnosis and treatment of severe talar neck fracture. METHODS: Using the multi-slice spiral CT image 3D reconstruction technique, we analysed 11 cases of talar neck fracture. The fractures were reduced and fixed through a minimal incision and internal fixation with titanium cannulated lag screws. RESULTS: In the 11 cases, the results of CT image 3D reconstruction were in concordance with plain radiograph in 6 case of Hawkins type II. And the remaining 5 cases of Hawkins types III and IV could not be classified exactly only by radiographs, one of whom was misdiagnosed. After using the CT image 3D reconstruction, the 5 cases were classified exactly before osteosynthesis. The classifications of these 11 cases were confirmed finally by surgical findings. The duration of operation were 45-140 min, averaging 81 min (including the duration of C-arm fluoroscopy). X-ray exposure time was 6-58 seconds, averaging 22 seconds. The blood loss was less than 100 ml. The fracture union was achieved in 3 months. No nonunion, talus avascular necrosis or joint surface collapse occurred. Postoperative follow-up was from 1 to 25 months. According to Hawkins score, excellent result was found in 6 type II cases and 1 type III case; good result in 1 type III case with both medial and lateral malleolar fracture, 1 type III with medial malleolus fractures and 1 open type III; fair result in 1 open type IV with lateral malleolus fracture. CONCLUSIONS: By using the multi-slice spiral CT image 3D reconstruction associated with radiography to diagnose and treat severe talar neck fractures, the accuracy of diagnosis can be improved obviously. Based on this technique, more consummate operational plan can be designed and performed so as to achieve a better therapeutic effect.

Adult↗

Adaptation of salt-tolerant Myxococcus strains and their motility systems to the ocean conditions.

More and more studies have indicated that myxobacteria are able to live in seawater conditions, which, however, can decrease the fruiting body formation ability and also the adventurous (A) and social (S) motility systems of the myxobacteria. To learn the adaptation mechanism of the salt-tolerant myxobacteria to marine conditions, we analyzed 10 salt-tolerant Myxococcus strains of their fruiting body formation and motility. The isolates were from marine samples and possessed different levels of salt tolerance. They had the dual motility system and formed fruiting bodies in the presence of suitable seawater concentrations. Some high salt-tolerant strains even lost their fruiting abilities in the absence of seawater. In response to the presence of seawater, the S-motility was found to be increased in the high salt-tolerants but decreased in the low salt-tolerants. The A-motility, on the other hand, was observed in all the salt-tolerant Myxococcus strains, but increased or decreased in response to the presence of seawater. Perceived shifts of fruiting body formation abilities and motilities discovered in the salt-tolerant Myxococcus strains suggested an ecological adaptation of myxobacterial social behaviors to the marine environments.

Adaptation, Physiological↗

Acceleration after-effects on learning and memory in rats: +10 Gz or +6 Gz for 3 min.

High sustained positive Gz (+Gz) exposures have been shown to have a pathophysiological impact on the brain in rats. However, the consequence for brain function such as learning and memory remains elusive. In the present study, we investigated locomotor activity, learning ability and memory in rats over 6 days (d) following +6 Gz/3 min and +10 Gz/3 min exposures. In an open field test, rats treated with +10 Gz showed a significant increase in the time spent in the center square immediately and 2d after exposure compared with control rats. In contrast, the number of grid crosses and number of rears of rats decreased significantly immediately after +6 Gz and +10 Gz exposures. In addition, a Y-maze test revealed that +Gz exposures reduced the number of correct responses and increased total reaction time in rats, and the number of correct responses was negatively correlated with the total reaction time in all groups throughout the period of study. Moreover, the passive avoidance test exhibited that the latency increased significantly on 0 d and decreased significantly on 6 d after +Gz exposures compared with control. Thus, +6 Gz/3 min and +10 Gz/3 min exposures may transiently decrease locomotor activity, impair learning, and induce a deficit in memory retention in rats.

Acceleration↗

Dietary anthocyanin-rich tart cherry extract inhibits intestinal tumorigenesis in APC(Min) mice fed suboptimal levels of sulindac.

A promising approach for cancer chemoprevention might be a combination therapy utilizing dietary phytochemicals and anticarcinogenic pharmaceuticals at a suboptimal dosage to minimize any potential adverse side effects. To test this hypothesis, various dosages of anthocyanin-rich tart cherry extract were fed in combination with suboptimal levels of the nonsteroidal anti-inflammatory drug sulindac to APCMin mice for 19 weeks. By the end of the feeding period, fewer mice that were fed the anthocyanin-rich extract in combination with sulindac lost more than 10% of body weight than mice fed sulindac alone. Mice that were fed anthocyanin-rich extract (at any dose) in combination with sulindac had fewer tumors and a smaller total tumor burden (total tumor area per mouse) in the small intestine when compared to mice fed sulindac alone. These results suggest that a dietary combination of tart cherry anthocyanins and sulindac is more protective against colon cancer than sulindac alone.

Adenomatous Polyposis Coli↗

Conduction mechanism of Aviram-Ratner rectifiers with single pyridine-sigma-C(60) oligomers.

We present the electron transport of pyridyl aza[60]fulleroid oligomers, abbreviated as C(60)NPy, which is based on the donor-barrier-acceptor (D-sigma-A) architecture, at a single molecular scale using scanning tunneling microscopy. A rectifying effect is observed in the current-voltage characteristics. The theoretical calculation shows that the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) are well localized either on the Py moiety (donor) or on the C(60) moiety (acceptor), indicating the sigma-bridge decouples the LUMO and the HOMO of the donor and the acceptor, respectively. This structure accords well with the unimolecular rectifying model proposed by Aviram and Ratner [Chem. Phys. Lett. 1974, 29, 277]. The mechanism of the rectifying effect is understood by analyzing in detail the electron transport through energy levels of the donor and the acceptor of the C(60)NPy molecules. By directly comparing the experimental conductance peaks and the calculated density of states of the C(60)NPy, we find that the observed rectification is attributed to the asymmetric positioning of the LUMOs and the HOMOs of both sides of the acceptor and the donor of the C(60)NPy molecules with respect to the Fermi level of the electrodes. When a main voltage drop is over the molecule-electrode vacuum junction but a small fraction over the molecule itself, the shift of the energy levels between the donor and the acceptor will be small. This behavior deviates from the original proposal by Aviram and Ratner in which a large shift of the energy level is expected.

Journal Article↗

Enhanced effect of fluorescent whitening agent on peroral infection for recombinant baculovirus in the host Bombyx mori L.

The low efficiency of the oral infectivity of recombinant polyhedrin-negative baculovirus is a major bottleneck in the application of the baculovirus expression system in the silkworm (Bombyx mori L). In this study, the effects of a fluorescent whitening agent on improving the oral infection for the recombinant Bombyx mori nuclear polyhedrosis virus in silkworm larva and their possible mechanism were investigated. The results showed that the peroral infection can be remarkably enhanced by adding VBL into the larval artificial diet. The maximum infection rate reached as high as 90% with the concentration of VBL (1%), which was then considered as optimal. The total protease activity and pH value of the larval intestinal juice were found to be lower when compared to the control, indicating an abnormal physiological change of the larval digestive system by VBL, which, in turn, resulted in improved peroral infection of recombinant virus.

6-Phytase↗

The serotonin 5-HT1D receptor gene and attention-deficit hyperactivity disorder in Chinese Han subjects.

Attention-deficit/hyperactivity disorder (ADHD) is a heritable disease. Serotonin is one of the neurotransmitters involved in the etiology of ADHD. Serotonin-1D receptors are autoreceptors which can regulate the release of serotonin in brain, so the HTR1D gene may be predisposing. The current study genotyped two variants of HTR1D gene in 272 ADHD trios of Chinese ethnicity, that is 1350T > C in the coding region and 1236A > G in 3'-UTR by the use of transmission disequilibrium test (TDT). The A allele of the 1236A > G polymorphism exhibited both a trend toward preferential transmission to ADHD probands (chi2 = 3.815, P = 0.051) and a significant preferential transmission to probands of ADHDC (chi2 = 4.198, P = 0.040). Additional polymorphisms in this gene need to be studied further.

Asian People↗