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result(s) for
"Wu, Jiandong"
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Recent advances in acoustofluidic separation technology in biology
2022
Acoustofluidic separation of cells and particles is an emerging technology that integrates acoustics and microfluidics. In the last decade, this technology has attracted significant attention due to its biocompatible, contactless, and label-free nature. It has been widely validated in the separation of cells and submicron bioparticles and shows great potential in different biological and biomedical applications. This review first introduces the theories and mechanisms of acoustofluidic separation. Then, various applications of this technology in the separation of biological particles such as cells, viruses, biomolecules, and exosomes are summarized. Finally, we discuss the challenges and future prospects of this field.
Journal Article
Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway
2017
Development of novel anti-influenza A virus (IAV) drugs with high efficiency and low toxicity is critical for preparedness against influenza outbreaks. Herein, we investigated the anti-IAV activities and mechanisms of fucoidan
in vitro
and
in vivo
. The results showed that a fucoidan KW derived from brown algae
Kjellmaniella crassifolia
effectively blocked IAV infection
in vitro
with low toxicity. KW possessed broad anti-IAV spectrum and low tendency of induction of viral resistance, superior to the anti-IAV drug amantadine. KW was capable of inactivating virus particles before infection and blocked some stages after adsorption. KW could bind to viral neuraminidase (NA) and inhibit the activity of NA to block the release of IAV. KW also interfered with the activation of EGFR, PKCα, NF-κB, and Akt, and inhibited both IAV endocytosis and EGFR internalization in IAV-infected cells, suggesting that KW may also inhibit cellular EGFR pathway. Moreover, intranasal administration of KW markedly improved survival and decreased viral titers in IAV-infected mice. Therefore, fucoidan KW has the potential to be developed into a novel nasal drop or spray for prevention and treatment of influenza in the future.
Journal Article
Comprehensive multi-omics and machine learning framework for glioma subtyping and precision therapeutics
2025
Glioma is a highly heterogeneous and aggressive brain tumour that demands an integrated understanding of its molecular and immunological landscape. We collected multi-omics data from 575 TCGA diffuse-glioma patients (156 IDH-wild-type WHO-grade 4 glioblastomas and 419 IDH-mutant WHO-grade 2/3 diffuse gliomas) together with two validation cohorts (CGGA n = 970; GEO n = 110). Using the MOVICS framework, we derived three integrative molecular subtypes—CS1, CS2 and CS3. Ten machine-learning algorithms in MIME were benchmarked, and the Lasso + SuperPC combination yielded an eight-gene GloMICS (Glioma Multi-Omics Consensus Signature) prognostic score. The subtypes display discrete biology: CS1 (astrocyte-like) is characterized by glial lineage features, immune-regulatory signaling, and relatively favorable prognosis; CS2 (basal-like/mesenchymal) shows epithelial-mesenchymal transition, stromal activation, and high immune infiltration, including PD-L1 expression; CS3 (proneural-like/IDH-mut metabolic) exhibits metabolic reprogramming (OXPHOS, hypoxia) and an immunologically cold tumour microenvironment (TME). CS2 is associated with the worst overall survival, whereas CS1 confers the most favourable outcome. Dual checkpoint blockade or T-cell-rejuvenation strategies may benefit CS2 tumours, while metabolic inhibitors could prove effective in CS3. The eight-gene GloMICS score outperformed 95 published prognostic models (C-index 0.74–0.66 across TCGA, CGGA and GEO). TME deconvolution, immune checkpoint profiling and TIDE analysis indicate that high-risk GloMICS tumours harbour immunosuppressive fibroblast-rich niches and exhausted CD8⁺ T cells. Connectivity-map screening nominated dabrafenib, irinotecan and three additional CTRP/PRISM compounds as candidate agents for the high-risk group. Our study establishes robust glioma subtypes and a transferable prognostic signature, offering a blueprint for biomarker-guided therapy. Future work should include single-cell and immunohistochemical validation of subtype hallmarks and prospective trials stratified by GloMICS score.
Journal Article
Lab-on-a-Chip Platforms for Detection of Cardiovascular Disease and Cancer Biomarkers
2017
Cardiovascular disease (CVD) and cancer are two leading causes of death worldwide. CVD and cancer share risk factors such as obesity and diabetes mellitus and have common diagnostic biomarkers such as interleukin-6 and C-reactive protein. Thus, timely and accurate diagnosis of these two correlated diseases is of high interest to both the research and healthcare communities. Most conventional methods for CVD and cancer biomarker detection such as microwell plate-based immunoassay and polymerase chain reaction often suffer from high costs, low test speeds, and complicated procedures. Recently, lab-on-a-chip (LoC)-based platforms have been increasingly developed for CVD and cancer biomarker sensing and analysis using various molecular and cell-based diagnostic biomarkers. These new platforms not only enable better sample preparation, chemical manipulation and reaction, high-throughput and portability, but also provide attractive features such as label-free detection and improved sensitivity due to the integration of various novel detection techniques. These features effectively improve the diagnostic test speed and simplify the detection procedure. In addition, microfluidic cell assays and organ-on-chip models offer new potential approaches for CVD and cancer diagnosis. Here we provide a mini-review focusing on recent development of LoC-based methods for CVD and cancer diagnostic biomarker measurements, and our perspectives of the challenges, opportunities and future directions.
Journal Article
The 3-O-sulfation of heparan sulfate modulates protein binding and lyase degradation
by
Wolfert, Margreet A.
,
Chopra, Pradeep
,
Joshi, Apoorva
in
Acetylglucosamine - chemistry
,
Acetylglucosamine - metabolism
,
Antithrombin III - chemistry
2021
Humans express seven heparan sulfate (HS) 3-O-sulfotransferases that differ in substrate specificity and tissue expression. Although genetic studies have indicated that 3-O-sulfated HS modulates many biological processes, ligand requirements for proteins engaging with HS modified by 3-O-sulfate (3-OS) have been difficult to determine. In particular, the context in which the 3-OS group needs to be presented for binding is largely unknown. We describe herein a modular synthetic approach that can provide structurally diverse HS oligosaccharides with and without 3-OS. The methodology was employed to prepare 27 hexasaccharides that were printed as a glycan microarray to examine ligand requirements of a wide range of HS-binding proteins. The binding selectivity of antithrombin-III (AT-III) compared well with anti-Factor Xa activity supporting robustness of the array technology. Many of the other examined HS-binding proteins required an IdoA2S-GlcNS3S6S sequon for binding but exhibited variable dependence for the 2-OS and 6-OS moieties, and a GlcA or IdoA2S residue neighboring the central GlcNS3S. The HS oligosaccharides were also examined as inhibitors of cell entry by herpes simplex virus type 1, which, surprisingly, showed a lack of dependence of 3-OS, indicating that, instead of glycoprotein D (gD), they competitively bind to gB and gC. The compounds were also used to examine substrate specificities of heparin lyases, which are enzymes used for depolymerization of HS/heparin for sequence determination and production of therapeutic heparins. It was found that cleavage by lyase II is influenced by 3-OS, while digestion by lyase I is only affected by 2-OS. Lyase III exhibited sensitivity to both 3-OS and 2-OS.
Journal Article
Locking interstitial hydrogen atoms in Pd metallenes for efficient oxygen reduction reaction
2025
Palladium hydride (PdH
x
) metallenes are efficient electrocatalysts for the oxygen reduction reaction (ORR) due to their high atomic utilization and optimized oxygen binding energies modulated by interstitial hydrogen. However, their practical application is restricted by the highly unstable nature of interstitial hydrogen at working temperatures around 353 K. Here, we report that the use of Mn effectively locks hydrogen atoms within the Pd metallenes lattice, resulting in high alkaline ORR performance across a temperature range of 303–353 K. In contrast, the ORR activity of PdH
x
metallenes declines sharply with increasing temperature. At 353 K, the mass activity of PdMnH
x
metallenes at 0.95 V reaches 1.41 A mg
−
1
, which is 14.1 times higher than that of PdH
x
metallenes. Multiple spectroscopic analyses and theoretical calculations reveal that strong electronic interactions within the immiscible Pd-Mn alloy are critical for locking interstitial hydrogen, thereby enhancing the ORR activity under high temperatures.
The authors present a Mn incorporation strategy to enhance the stability of PdH
x
metallenes by locking interstitial H atoms via strong electronic interactions in the immiscible alloy, resulting in an improved alkaline oxygen reduction reaction activity and stability at working temperature around 353 K.
Journal Article
Atomic Dispersed Hetero-Pairs for Enhanced Electrocatalytic CO2 Reduction
2024
HighlightsA unique atomic dispersed hetero-pair was successfully synthesized, consisting of Mo-Fe di-atoms anchored on N-doped carbon carrier.This strategy breaks the linear scaling relationships of electrocatalytic CO2 reduction by simultaneously regulating the *COOH adsorption energy and *CO desorption energy.The as-prepared MoFe–N–C exhibits excellent performance for CO2RR to CO with a high turnover frequency (TOF) of 3336.21 h−1, CO Faradaic efficiency (FECO) of 95.96% at − 0.60 V (versus RHE) and outstanding stability.Electrochemical carbon dioxide reduction reaction (CO2RR) involves a variety of intermediates with highly correlated reaction and ad-desorption energies, hindering optimization of the catalytic activity. For example, increasing the binding of the *COOH to the active site will generally increase the *CO desorption energy. Breaking this relationship may be expected to dramatically improve the intrinsic activity of CO2RR, but remains an unsolved challenge. Herein, we addressed this conundrum by constructing a unique atomic dispersed hetero-pair consisting of Mo-Fe di-atoms anchored on N-doped carbon carrier. This system shows an unprecedented CO2RR intrinsic activity with TOF of 3336 h−1, high selectivity toward CO production, Faradaic efficiency of 95.96% at − 0.60 V and excellent stability. Theoretical calculations show that the Mo-Fe diatomic sites increased the *COOH intermediate adsorption energy by bridging adsorption of *COOH intermediates. At the same time, d-d orbital coupling in the Mo-Fe di-atom results in electron delocalization and facilitates desorption of *CO intermediates. Thus, the undesirable correlation between these steps is broken. This work provides a promising approach, specifically the use of di-atoms, for breaking unfavorable relationships based on understanding of the catalytic mechanisms at the atomic scale.
Journal Article
Boosting oxygen reduction performances in Pd-based metallenes by co-confining interstitial H and p-block single atoms
2025
The efficiency of the oxygen reduction reaction (ORR) is limited by the scaling relationship in the conventional oxygen associative pathway. To break such limitations, we present an approach to effectively activate the oxygen dissociative pathway through co-confining single
p
-block (In, Sn, Pb) atoms and interstitial H atoms within Pd metallenes, leading to good ORR performance. PdPbH
x
metallenes exhibit a high mass activity of 1.36 A mg
−1
at 0.95 V (vs. RHE), which is 46.9 times higher than that of the benchmark Pt/C. The minimal performance decay after 50,000 potential cycles confirms a good stability. In situ vibrational spectroscopy investigations and theoretical calculations highlight that interstitial H atoms facilitate the direct dissociation of O
2
while single Pb atoms enhance O
2
adsorption strength. The electroactive PdPbH
x
metallenes is attributed to the up-shifted Pd-4
d
orbitals induced by H and Pb atoms. This research supplies critical inspiration for developing highly efficient ORR electrocatalysts.
The oxygen reduction reaction (ORR) is limited by the scaling relationship in the conventional oxygen associative pathway. In this study, single p-block atoms and interstitial H are incorporated into Pd metallenes favoring the direct dissociation mechanism, leading to high alkaline ORR performance.
Journal Article
The DOF-Domain Transcription Factor ZmDOF36 Positively Regulates Starch Synthesis in Transgenic Maize
2019
Starch synthesis is a complex process that influences crop yield and grain quality in maize. Many key enzymes have been identified in starch biosynthesis; however, the regulatory mechanisms have not been fully elucidated. In this study, we identified a DOF family gene,
, through transcriptome sequencing analysis. Real-time PCR indicated that
was highly expressed in maize endosperm, with lower expression in leaves and tassels.
is a typical DOF transcription factor (TF) that is localized to the nucleus and possesses transcriptional activation activity, and its transactivation domain is located in the C-terminus (amino acids 227-351). Overexpression of
can increase starch content and decrease the contents of soluble sugars and reducing sugars. In addition, abnormal starch structure in transgenic maize was also observed by scanning electron microscopy (SEM). Furthermore, the expression levels of starch synthesis-related genes were up-regulated in
-expressing transgenic maize. ZmDOF36 was also shown to bind directly to the promoters of six starch biosynthesis genes,
,
,
,
,
, and
in yeast one-hybrid assays. Transient expression assays showed that ZmDOF36 can activate the expression of
and
in tobacco leaves. Collectively, the results presented here suggest that ZmDOF36 acts as an important regulatory factor in starch synthesis, and could be helpful in devising strategies for modulating starch production in maize endosperm.
Journal Article
Regulation of Drought and Salt Tolerance by OsSKL2 and OsASR1 in Rice
2022
Abiotic stresses such as salinity and drought greatly impact the growth and production of crops worldwide. Here, a shikimate kinase-like 2 (SKL2) gene was cloned from rice and characterized for its regulatory function in salinity and drought tolerance. OsSKL2 was localized in the chloroplast, and its transcripts were significantly induced by drought and salinity stress as well as H2O2 and abscisic acid (ABA) treatment. Meanwhile, overexpression of OsSKL2 in rice increased tolerance to salinity, drought and oxidative stress by increasing antioxidant enzyme activity, and reducing levels of H2O2, malondialdehyde, and relative electrolyte leakage. In contrast, RNAi-induced suppression of OsSKL2 increased sensitivity to stress treatment. Interestingly, overexpression of OsSKL2 also increased sensitivity to exogenous ABA, with an increase in reactive oxygen species (ROS) accumulation. Moreover, OsSKL2 was found to physically interact with OsASR1, a well-known chaperone-like protein, which also exhibited positive roles in salt and drought tolerance. A reduction in ROS production was also observed in leaves of Nicotiana benthamiana showing transient co-expression of OsSKL2 with OsASR1. Taken together, these findings suggest that OsSKL2 together with OsASR1 act as important regulatory factors that confer salt and drought tolerance in rice via ROS scavenging.
Journal Article