Biomedical subjects

Jian Ma

Publications and source records attributed to Jian Ma.

4 recordsLinked to original sources

PubMed2026

Ancient DNA unveils distinctive ancestries in the Bronze and Iron Ages of East Tianshan.

The East Tianshan Mountains occupy a key corridor between Central and East Asia, but their population history remains poorly understood. Here we report genome-wide data from 135 ancient individuals from 11 archaeological sites. We identify a previously unrecognized Bronze Age admixture between populations related to Yellow River millet farmers and steppe pastoralists associated with the Chemurchek culture. In contrast, we find little genetic contribution from contemporaneous middle-to-late Bronze Age steppe pastoralists, despite their eastward expansion across the Eurasian Steppe. By the Iron Age, regional populations had become more heterogeneous, incorporating additional eastern and steppe-related sources while retaining variable contributions from Early Bronze Age groups. These results reveal sustained demographic interactions in eastern Central Asia nearly 1800 years preceding the establishment of the historic Silk Road.

DNA, Ancient↗

PubMed2026

Dual HBV cccDNA-linked HiBiT reporter hepatocyte models for screening of candidate cccDNA modulators.

Chronic hepatitis B remains difficult to cure because the viral covalently closed circular DNA (cccDNA) minichromosome can persist and sustain viral transcription, creating a need for scalable, reporter readouts that facilitate early discovery of cccDNA-modulating agents. Here, we developed two complementary hepatocyte HiBiT reporter models: a replication-competent HBV reporter in HepaRG cells (HepaRG-Hibit16), in which a secreted split-NanoLuc HiBiT signal is linked to cccDNA-associated expression, and a Cre/Lox-based recombinant cccDNA (rcccDNA) reporter in HepG2 cells (HepG2-Rccc1a) that rapidly generates rcccDNA with a matched HiBiT readout. Screening of 1,403 FDA-approved compounds across both models identified 13 concordant, non-cytotoxic hits. Palovarotene, a retinoic acid receptor-γ agonist, was selected as an exemplar concordant hit and reduced HBV antigens, HBV DNA, and cccDNA and inhibited HBV infection in multiple hepatocyte-based in vitro systems without overt cytotoxicity at the tested concentrations. Together, this dual-reporter strategy supports efficient cross-model triage of candidate cccDNA modulators for subsequent orthogonal validation.

Humans↗

PubMed2026

pH Tunes the DNA Repair Efficiency and Strand Preference of the AlkB Family Enzymes.

AlkB-family Fe(II)/2-oxoglutarate-dependent dioxygenases repair alkylated nucleic acid lesions through oxidative dealkylation and play important roles in genome maintenance. 1-Methyl-2'-deoxyadenosine (1mA) and 3-methyl-2'-deoxycytidine (3mC) are well-established substrates of AlkB, ALKBH2, and ALKBH3. Although these enzymes have been extensively studied, the influence of proton concentration (pH) on their catalytic behavior and strand preference remains poorly defined. Here, we systematically examined how pH modulates the activity of the prototypical bacterial AlkB and the human homologues ALKBH2 and ALKBH3 using defined DNA substrates in both single-stranded (ssDNA) and double-stranded (dsDNA) contexts containing 1mA and 3mC lesions. Across a broad pH range, all three enzymes mainly exhibit bell-shaped activity profiles with distinct optima. The prevailing view in the field is that AlkB preferentially repairs these lesions in ssDNA, ALKBH2 favors dsDNA, and ALKBH3 prefers ssDNA. However, our results demonstrate that pH influences the catalytic efficiency and strand utilization in a substrate- and enzyme-dependent manner. AlkB maintains a consistent ssDNA preference for 3mC but exhibits variable strand preference for 1mA at different pH values. ALKBH2 retains a strong dsDNA preference for 1mA across all conditions but shows a clear pH-dependent strand switch for 3mC, favoring ssDNA under acidic conditions and preferring dsDNA at neutral to alkaline pH conditions. In contrast, ALKBH3 consistently favors ssDNA for 3mC but exhibits pH-dependent strand preference for 1mA. Our results show that the reported strand preferences largely hold at pH 7.0-8.0 but are not complete, as strand utilization and pH optima vary by enzyme and substrate. The observations demonstrate that proton availability strongly influences AlkB-family catalysis and is an important factor in how these enzymes process damaged DNA. These findings may also aid the optimization of AlkB-based protein engineering and sequencing technologies.

Hydrogen-Ion Concentration↗

PubMed2026

Seed-type vacuolar processing enzymes recognize the 619th asparagine residue to posttranslationally cleave the HMW-GS 1Dy10-m619SN allele.

High molecular weight glutenin subunits (HMW-GSs) are critical grain storage proteins in wheat, which govern its unique processing quality. A HMW-GS 1Dy10 allele variant (1Dy10-m619SN), carrying a serine-to-asparagine substitution at the 619th residue, undergoes partial posttranslational cleavage. This modification leads to improved cookie-making quality. However, the enzymes mediating this cleavage remain unknown. In this study, we identified vacuolar processing enzymes (VPEs) as candidates for 1Dy10-m619SN processing using TurboID-based proximity labeling and RNA-seq analysis. In vitro cleavage assays confirmed that VPEs catalyzed 1Dy10-m619SN cleavage. Phylogenic analysis revealed that there are two seed-type VPEs in wheat, TaVPEI and TaVPEII, with TaVPEI being further subdivided into TaVPEI-1, TaVPEI-2, and TaVPEI-3. Despite sharing conserved catalytic domains, these isoforms display distinct temporal expression patterns, with TaVPEI-1 expression showing the strongest correlation with the posttranslational cleavage of 1Dy10-m619SN. TaVPEI-1 protein is localized to the vacuole, the well-known deposition site for HMW-GSs. Overexpression of TaVPEI-1 in wheat enhances the 1Dy10-m619SN cleavage. Collectively, these findings demonstrate that the seed-type VPEs in wheat are responsible for the posttranslational cleavage of 1Dy10-m619SN, which provides new insights into the molecular basis of wheat's unique processing quality.

Triticum↗