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Biology subjects

wang, b.

Publications and source records attributed to wang, b..

6 recordsLinked to original sources

An efficient and stable ascorbate/O2-driven route for L-DOPA synthesis by heme-dependent tyrosine hydroxylase

L-DOPA is a key therapeutic agent for Parkinsons disease, with growing demand due to global population aging. Here we report that heme-dependent tyrosine hydroxylase (TyrH) can utilize an ascorbate/O2 system--as an alternative to H2O2--to synthesize L-DOPA with markedly enhanced operational stability. While exogenous H2O2 rapidly inactivates TyrH within minutes, sodium ascorbate (NaAsc) enables sustained catalysis for up to 24 h, surpassing the H2O2-driven yield after only 30 min. UV-vis spectroscopy confirms that H2O2 readily degrades the heme center, whereas the heme remains intact in the presence of NaAsc. QM/MM simulations reveal that in situ generated H2O2 leads to the active species of Compound I for tyrosine hydroxylation. Through systematic optimization, we establish efficient reaction conditions (40 {micro}M TyrH, 1 mM L-Tyr, 100 mM NaAsc, pH 8.5, 40 {degrees}C), achieving >95% conversion of L-Tyr to L-DOPA within 2 h. This work not only provides a robust and sustainable biocatalytic route for L-DOPA production but also highlights the broader applicability of the ascorbate/O2 pathway in heme-enzyme catalysis.

biochemistry↗

Physics-informed multi-encoder adaptive optics enables rapid aberration correction for intravital microscopy of deep complex tissue

Tissue-induced optical aberrations fundamentally constrain intravital microscopy in deep or complex biological specimens. While adaptive optics (AO) can compensate for these aberrations, conventional AO methods are limited by either guide-star dependency or slow correction speeds. Here, we develop MeNet-AO, a multi-encoder network-based AO method that enables rapid, guide-star-free aberration correction. By integrating a noise-resilient, structure-independent feature extraction model with a physics-informed multi-encoder architecture, MeNet-AO jointly decodes multiple large-amplitude aberration modes from wavefront-modulated image pairs, achieving an effective balance between prediction accuracy and temporal efficiency. Validated in living organisms, MeNet-AO improves fluorescence imaging in zebrafish brain and eye, enhances neuronal calcium transients and direction selectivity in mouse visual cortex, and enables subcellular-resolution microglial calcium imaging through thinned-skull windows - revealing spatiotemporally heterogeneous signaling patterns previously obscured by skull aberration. The speed and robustness of MeNet-AO in low-signal and scattering conditions establish it as a versatile platform for dynamic subcellular imaging deep within native tissue environments.

bioengineering↗

A Phospho-Switch for Cell Fate Control

Cell fate control is thought to be complex, likely involving both cell intrinsic and extrinsic factors, and remains ill-defined at the molecular level. Here we show a phospho-switch controls cell fate both in vitro and in vivo. We first show that SALL4 is phosphorylated at multiple sites, but only T903 as the primary one as SALL4T903A lost BAF interaction and [~]90% activity in reprogramming. Mechanistically, we demonstrate that SALL4pT903 is sensitive to BMP4 signaling through DUSP9 axis. Finally, we show by tetraploid embryo complementation that mESCs harboring SALL4T903A can sustain embryo development but with severe defects including cranial hypoplasia and flattened skull vault after birth. A genome wide search identifies 608 transcription factors harboring the same HTG motif sandwiched by two zinc fingers, suggesting that this phospho-switch may be a conserved mechanism to control cell fate. In briefA phosphorylation switch, pT903, in SALL4 governs cell fate by modulating BAF complex interaction in response to BMP4-DUSP9 signaling, as its dephosphorylation abrogates reprogramming and causes cranial defects in mice, suggesting that such switches may broadly regulate cell fate machinery. HighlightsO_LIA T903 phospho-switch in SALL4 gates BAF interaction to orchestrate gene activation and reprogramming C_LIO_LIBMP4-DUSP9 signaling converges on SALL4pT903 dephosphorylation to couple extracellular cues with cell fate determination C_LIO_LIDisrupting the SALL4-T903 phospho-switch causes severe postnatal developmental defects in mice. C_LIO_LIThe HTGE motif may function as a central switch on key transcription factors for sensing upstream signals C_LI

developmental biology↗

Analysis of Nutritional Components in Brown Sugar and Its Effects on Anti-fatigue, Alleviation of Qi Deficiency and Blood Stasis, and Antioxidant Effects

Brown sugar (BS), Red granulated sugar (RGS) and White sugar(WS) are three key sweeteners and food additives in China. Notably, BS possesses significant nutritional value and has been widely used in Chinese medicine for its supportive therapeutic properties.This study evaluated the anti-fatigue, the amelioration of qi deficiency and blood stasis, as well as the antioxidant activities of these sugars using a zebrafish model. BS and RGS demonstrated significantly greater efficacy than WS in terms of both anti-fatigue effects and amelioration of qi Deficiency and blood stasis in the zebrafish model. Antioxidant assays revealed that BS, RGS, and WS (500 g/mL) significantly enhanced superoxide dismutase (SOD) activity in zebrafish embryos compared with the control group. Furthermore, the mineral composition of sugar were determined. Nine mineral elements--potassium (K), calcium (Ca), sodium (Na), magnesium (Mg), iron (Fe), zinc (Zn), copper (Cu), phosphorus (P), and selenium (Se)--were analyzed. BS exhibited markedly higher concentrations of P, Ca, Fe, and Mg than RGS and WS, while selenium (detected at 50 mg/kg) was exclusively detected in BS. Intriguingly, RGS contained four-fold higher potassium levels than BS. Total polyphenol content, quantified by Folin-Ciocalteu assay, was 4.35 g/kg in BS and 1.53 g/kg in RGS, with no detectable polyphenols in WS.

biochemistry↗

Dissecting the genetic basis of the heterosis of Y900, an elite super-hybrid rice

Y900 is one of the top hybrid rice varieties with a yield exceeding 15 t/hm2. To dissect the mechanism of heterosis, the male parent line R900 and female parent line Y58S were sequenced using long-read and Hi-C technology. High-quality reference genomes of sizes of 396.41 Mb and 398.24 Mb were obtained for R900 and Y58S, respectively. Genome-wide variations between the parents were systematically identified, including 1,367,758 SNPs and 299,149 Indels. No megabase level structural variations exist. >75% of genes exhibited variation between the two parents. Compared with other two-line hybrids sharing the same female parent, the Geng/japonica-type genetic components from different male parents showed an increasing trend from phase 2-4 super-hybrid rice; Transcriptome analysis revealed that additive and dominance effects are the main genetic effects that constitute the heterosis of Y900. Allele-specific expression patterns and expression regulation patterns are quite dynamic in different tissues. For young panicle tissues, cis-regulation is dominant, while trans-regulation is more popular in leaf issues. Overdominance is more likely regulated by the trans-regulation mechanism. The differential gene expression and regulation pattern are closely related to Geng/japonica introgression. Additionally, R900 contained several excellent japonica haplotypes, such as NAL1, OsSPL13, Ghd8, OsBRI1, and DTH2, which make a good complement to Y58S. The fine tune mechanism through dynamic expression or regulation pattern change, especially on some key functional genes, is the base for heterosis.

plant biology↗

Transcriptome analysis reveals the main metabolic pathway of c-GMP induced by salt stress in tomato seedlings

Tomato is a model crop, as well as important food worldwide. In the arid areas, aggravation of soil salinity has become the primary problem that threatens the high yield in tomato production. As a second messenger substance, cyclic guanosine monophosphate (c-GMP) plays an indispensable role in plant response to salt stress through regulating cell processes to promote plant growth and development. However, this mechanism has not been fully explored in tomato seedlings. In this experiment, the tomato seeds were cultured in distilled water (CK), 20 M c-GMP (T1), 50 mM NaCl (T2), 20 M c-GMP + 50 mM NaCl (T3). The results show that 20 M c-GMP effectively alleviated the inhibition of 50 mM NaCl on tomato growth and development, inducing the expression of 1580 DEGs. 95 DEGs were up-regulated and 442 DEGs were down-regulated (CK vs T1), whereas in the T2 vs T3 comparison 271 DEGs were up-regulated and 772 DEGs were down-regulated. Based on KEGG analysis, the majority of DEGs were involved in metabolism; exogenous c-GMP induced significant enrichment of pathways associated with carbohydrates, phenylpropanoids and fatty acid metabolism. Most PMEs, acCoA, PAL, PODs, FADs, and AD were up-regulated, and GAPDHs, PL, PG, BXL4, and {beta}-G were down-regulated, which reduced susceptibility of tomato seedlings to salt and promoted their salt adaptation. The application of c-GMP promoted soluble sugar, flavonoids and lignin content, reduced accumulation of MDA, and enhanced the activity of POD. Thus, our results provide insights into the molecular mechanisms associated with salt tolerance of tomato seedlings.

physiology↗