Biomedical subjects

Cheng Li

Publications and source records attributed to Cheng Li.

At least 19 recordsLinked to original sources

PubMed2026

Precision Engineering of Evolution-Resilient Rice against Bacterial Blight.

The persistent conflict between rice and Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight, exemplifies a dynamic genetic arms race in agriculture. The cyclical deployment and erosion of major resistance (R) genes highlight the high adaptive potential of Xoo and the need for strategies that are durable rather than absolute. This review synthesizes a paradigm shift from reactive, single R-gene deployment toward proactive engineering of evolution-resilient resistance. We explore the molecular-genetic basis of Xoo adaptability, including TAL effector diversification, non-TAL virulence functions, genome variation, and immune suppression mechanisms. In response, we propose a framework for durable disease management with three connected components: precision disarmament through editing of susceptibility-gene effector-binding elements and executor/decoy designs; smart induction through targeted delivery and immune priming; and ecological fortification through protective microbiomes. We also discuss the limits, trade-offs, and field-validation requirements of these approaches. Integrating frontier technologies with evolutionary genetics, predictive genomics, and pathogen population dynamics can help develop rice varieties and deployment systems that are more difficult for Xoo populations to overcome.

CRISPR↗

PubMed2026

Minimal Transport Units Govern Oxygen-Defect Stabilization and Transport for Lightweight Solid Electrolytes.

Solid electrolytes are central to electrochemical energy technologies, including fuel cells, sensors, catalysis, membrane separation, and electrolyser. However, most established oxide-ion solid electrolytes are built around heavy B-site cations embedded in rigid and highly connected coordination frameworks, leading to widespread high-weight and sluggish ionic transport that is strongly coupled to large-amplitude lattice relaxations. This intrinsic challenge hinders further performance optimization and constrains the rational design of lightweight electrolytes. Herein, we propose a minimal transport unit-based design paradigm that combines simplified structural motifs with light-element chemistry, enabled by the exceptional flexibility of B-O polyhedra in coordination, rotation, deformation, and connectivity. As a proof of concept, Sc1- xZnxBO3- x /2, constructed from isolated BO3 units, exhibits high oxide ion conductivity (σ(1000°C) ∼ 1.5 × 10-2 S/cm), alongside excellent thermo-mechanical stability. Oxygen vacancies are stabilized through the formation of B2O5 units rather than isolated BO2 species. Long-range oxide-ion migration is mediated by dynamic oxygen exchange between minimal BO3 and B2O5 units via continuous breaking and reforming of B2O5 units, with transient BO2 configurations as intermediates. This study demonstrates minimal transport units as a governing principle for defect stabilization and ionic conduction in lightweight solid electrolytes, offering a general design framework for portable and scalable high-temperature energy technologies.

NMR spectroscopy and variable‐temperature P↗

PubMed2026

Antimony species-dependent enrichment and transcriptional activity of antibiotic and metal resistance genes in the gut microbiome of male mice.

The gut microbiome is a reservoir for antibiotic resistance genes (ARGs) and is sensitive to environmental pollutants. ARGs in environmental and host-associated microbiomes can be enriched by metal(loid)s through co-selection with metal resistance genes (MRGs). However, as a ubiquitous toxic metalloid, antimony (Sb) induced alterations of ARGs in the gut microbiome and the underlying mechanisms remain unclear. Here, by integrating genome-resolved metagenomics and metatranscriptomics, we characterized the genomic potential and transcriptional activity of ARGs and MRGs in the gut microbiome of mice exposed to Sb(III)- and Sb(V)-contaminated drinking water. We found that both Sb(III) and Sb(V) significantly increased ARGs abundance, whereas only Sb(III) enhanced ARGs transcription (288.40 ± 41.67 TPM, P < 0.05). Co-selection of ARGs and MRGs was observed through metagenome-assembled genomes (MAGs) analysis, and key taxa driving this process were identified (e.g., Eubacterium_J and Lachnospiraceae_COE1). Sb(III), but not Sb(V), induced co-regulation of macrolide-lincosamide-streptogramin resistance genes and arsRABC operon. A potentially higher risk of ARG dissemination under Sb(III) stress was suggested by the increased abundance and transcription of mobile genetic elements (MGEs). This study advances our understanding of the interactions between Sb and ARGs in the gut microbiome and highlights the potential chemical species-dependent enrichment and transcriptional activation of ARGs.

Antibiotic resistance gene↗

PubMed2026

Mulberry-derived endophytic Bacillus velezensis suppresses gray mold and promotes mulberry growth via reshaping the root metabolism and microbiome.

INTRODUCTION: Gray mold is an important fungal disease caused by Botrytis cinerea which threatens global agriculture. As chemical control faces limitations, biological control using Bacillus has gained attention for its environmental friendliness and growth promotion. However, their ecological basis and application potential in mulberry gray mold control remain insufficiently understood. OBJECTIVE: This study aimed to evaluate the biocontrol efficacy of the mulberry derived endophytic strain Bacillus velezensis ZJU_268 and to investigate its associated effects on plant growth, root-associated microbiomes, and metabolic profiles. METHODS: Greenhouse assays were combined with genomic and comparative genomic analyses, amplicon sequencing, non-targeted metabolomics, and functional validation of isolated microbes and metabolites to assess the effects of ZJU_268 and its cell free supernatant (CFS) on mulberry seedlings. RESULTS: This study isolated a mulberry derived endophytic bacterium, B. velezensis ZJU_268, which exhibits strong antifungal activity and reduces the incidence of gray mold in mulberry seedlings. Whole-genome sequencing and comparative genomic analyses revealed strain-specific regions and genes associated with root colonization, stress adaptation, and antimicrobial biosynthesis. Both live cells and CFS significantly promoted seed germination, seedling growth, and biomass accumulation in a dose dependent manner. Amplicon sequencing showed that ZJU_268 and its supernatant reshaped the mulberry root microbiome, enriching beneficial bacterial and fungal taxa while reducing potentially pathogenic members. Cultivable members of the enriched microbiota displayed strong antifungal activity against B. cinerea and promoted mulberry growth. Metabolomic profiling further showed that ZJU_268 and its supernatant were associated with marked metabolic shifts in mulberry roots, accompanied by the accumulation of selected metabolites that supported the growth of representative enriched isolates. CONCLUSIONS: This study demonstrates that ZJU_268 suppresses gray mold and promotes mulberry growth in association with direct antagonistic activity, microbiome restructuring, and holobiont-level metabolic shifts, providing a promising biological strategy for sustainable mulberry disease management.

Bacillusvelezensis↗

PubMed2026

Phosphorus modulates starch granule development and metabolic partitioning in wheat grain: Insights from SGAP proteomics and nutrition and processing quality.

This study investigates how phosphorus (P) levels are associated with carbon-nitrogen metabolism in wheat grains. Optimal P application (105 kg P₂O₅ ha⁻¹) was associated with enhanced pericarp-endosperm coordination, increased carbon allocation to the endosperm, and early B‑type starch granule formation. Starch granule‑associated protein (SGAP) proteomics showed that optimal P upregulated cytoskeletal and starch‑synthesis proteins bound to starch granules in the endosperm, while reducing storage protein degradation‑related SGAPs in the pericarp. These metabolic adjustments were correlated with increased grain‑filling intensity and duration, and were associated with the highest theoretical grain weight (50.70 mg). Furthermore, optimal P was associated with enrichment of amino acid biosynthesis pathways and with higher levels of essential amino acids (e.g., lysine and threonine by 17.0--26.8%) and an improved essential amino acid profile without altering total protein content. In contrast, excessive P (210 kg P₂O₅ ha⁻¹) was associated with disrupted inter‑tissue coordination but did not simply impair grain filling; instead, HP corresponded to a unique developmental program: it was linked to an early burst of C‑type starch granules (0∼5 µm) at 7 DPA, yet by maturity achieved the highest proportion of large A‑type granules (56.8%) and the highest total starch content (63.5%), together with elevated endosperm phosphorus at 14 DPA and enrichment of spliceosome‑related pathways. HP also showed higher levels of several functional amino acids (glutamate, cysteine, histidine, proline) compared to P0. However, HP was associated with a higher gliadin/globulin ratio and did not improve grain yield. These findings suggest that phosphorus supply is associated with grain quality through tissue‑specific metabolic reprogramming, and that precision management-rather than maximized application-warrants consideration for optimizing both yield and processing quality.

Triticum↗

PubMed2025

Anoikis classification of lung squamous cell carcinoma reveals correlation with clinical prognosis and immune characteristics.

BACKGROUND: Anoikis is a new mode of cell death that has been shown to correlate significantly with tumors. However, the clinical prognostic significance of anoikis in lung squamous cell carcinoma (LUSC) remains poorly studied. METHODS: The differentially expressed ARGs and candidate genes were selected by the differential analysis to construct a predictive model. Independent prognostic gene was determined by Cox and LASSO analysis and we used the HCC95 and NCI H520 cell line to verify the gene function. We used the data from TCGA, GEO, GeneCards, and Harmonizome databases to analyze the immune microenvironment, functional enrichment, and drug sensitivity analysis. RESULTS: We identified 717 differentially expressed and selected 3 ARGs (FADD, SNAI1, and BAG4) to construct a predictive model. We found that SNAI1 is an independent prognostic gene and confirmed that knocking out the SNAI1 inhibited the HCC95/NCI H520 cell proliferation. We used single-sample gene-set enrichment analysis (ssGSEA) to evaluate the immune infiltration based on the 3 ARG expression levels. We constructed a risk score and provided a visual representation of the prophetic implications of the ARGs-based signature through a nomogram. We found 15 susceptible drugs in the high-risk group and 15 sensitive drugs in the low-risk group by the drug sensitivity analysis. CONCLUSION: We used ARGs to construct a prognosis model for LUSC that can accurately predict the prognosis of LUSC patients. ARGs, especially SNAI1, play an essential role in developing LUSC. These findings could provide individualized treatment plans and new research ideas for LUSC patients.

Humans↗

PubMed2025

The telomere-to-telomere genome of Sanicula chinensis unveils genetic underpinnings of low furanocoumarin diversity and content in one basal lineage of Apiaceae.

Furanocoumarins are specialized defense compounds in Apiaceae, but the evolutionary path of their biosynthesis is not well understood. We generated a telomere-to-telomere (T2T) genome for Sanicula chinensis, an early-diverging species within the Saniculoideae subfamily, to explore its evolution. Comparative genomics revealed that S. chinensis and Apioideae species each underwent unique whole-genome duplication (WGD). Unlike most species in the Apioideae subfamily, S. chinensis produces a limited diversity and content of furanocoumarins but shows high esculetin levels. This metabolic profile likely stems from three genetic factors: elevated expression of p-Coumaroyl ester 3'-hydroxylase (C3'H) and hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT), which shift the metabolic pathway toward simple coumarins; the absence of a key biosynthetic gene cluster, including prenyltransferase (PT) and p-coumaroyl-CoA 2'-hydroxylase (C2'H), found in Apioideae; and incomplete or inactive PT enzymes in S. chinensis. Our results not only shed light on the evolutionary history of furanocoumarin biosynthesis in Apiaceae, but also provide avenues for tailoring furanocoumarin content for agricultural or medical applications in plants.

Furocoumarins↗

PubMed2006

Nanoindentation differentiates tissue-scale functional properties of native articular cartilage.

Cartilage mechanical properties are typically tested at the macroscale. To demonstrate the ability of nanoindentation to characterize in situ articular cartilage properties at the tissue scale, we investigated the local structure-property relationships of intact articular cartilage of a normal rabbit metacarpophalangeal joint. We calculated the mechanical parameters of stiffness, S, resistance to penetration, R, and volumetric creep strain, dV/V, from nanoindentation of the articular surface at specific regions of interest. We measured morphological parameters of superficial zone thickness, middle zone thickness, total uncalcified thickness, and cell density from corresponding regions with light and polarized light microscopy. Mechanical parameters were compared to morphological parameters. There were significant positive correlations (r = 0.98, p < 0.05) between superficial zone thickness and both S and R. However, we found no significant correlation between dV/V and the zone sizes. There were moderate, negative correlations between cell density and both S and R, suggesting an effect of cell volume on cartilage behavior at the tissue scale. We opine that the superficial zone plays important role in load support, as evidenced by correlations between zone size and intact cartilage mechanical properties.

Animals↗

PubMed2006

Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma.

Multiple myeloma is characterized by genomic alterations frequently involving gains and losses of chromosomes. Single nucleotide polymorphism (SNP)-based mapping arrays allow the identification of copy number changes at the sub-megabase level and the identification of loss of heterozygosity (LOH) due to monosomy and uniparental disomy (UPD). We have found that SNP-based mapping array data and fluorescence in situ hybridization (FISH) copy number data correlated well, making the technique robust as a tool to investigate myeloma genomics. The most frequently identified alterations are located at 1p, 1q, 6q, 8p, 13, and 16q. LOH is found in these large regions and also in smaller regions throughout the genome with a median size of 1 Mb. We have identified that UPD is prevalent in myeloma and occurs through a number of mechanisms including mitotic nondisjunction and mitotic recombination. For the first time in myeloma, integration of mapping and expression data has allowed us to reduce the complexity of standard gene expression data and identify candidate genes important in both the transition from normal to monoclonal gammopathy of unknown significance (MGUS) to myeloma and in different subgroups within myeloma. We have documented these genes, providing a focus for further studies to identify and characterize those that are key in the pathogenesis of myeloma.

Bone Marrow↗

PubMed2006

Inferring loss-of-heterozygosity from unpaired tumors using high-density oligonucleotide SNP arrays.

Loss of heterozygosity (LOH) of chromosomal regions bearing tumor suppressors is a key event in the evolution of epithelial and mesenchymal tumors. Identification of these regions usually relies on genotyping tumor and counterpart normal DNA and noting regions where heterozygous alleles in the normal DNA become homozygous in the tumor. However, paired normal samples for tumors and cell lines are often not available. With the advent of oligonucleotide arrays that simultaneously assay thousands of single-nucleotide polymorphism (SNP) markers, genotyping can now be done at high enough resolution to allow identification of LOH events by the absence of heterozygous loci, without comparison to normal controls. Here we describe a hidden Markov model-based method to identify LOH from unpaired tumor samples, taking into account SNP intermarker distances, SNP-specific heterozygosity rates, and the haplotype structure of the human genome. When we applied the method to data genotyped on 100 K arrays, we correctly identified 99% of SNP markers as either retention or loss. We also correctly identified 81% of the regions of LOH, including 98% of regions greater than 3 megabases. By integrating copy number analysis into the method, we were able to distinguish LOH from allelic imbalance. Application of this method to data from a set of prostate samples without paired normals identified known regions of prevalent LOH. We have developed a method for analyzing high-density oligonucleotide SNP array data to accurately identify of regions of LOH and retention in tumors without the need for paired normal samples.

Alleles↗

PubMed2006

Adjusting batch effects in microarray expression data using empirical Bayes methods.

Non-biological experimental variation or "batch effects" are commonly observed across multiple batches of microarray experiments, often rendering the task of combining data from these batches difficult. The ability to combine microarray data sets is advantageous to researchers to increase statistical power to detect biological phenomena from studies where logistical considerations restrict sample size or in studies that require the sequential hybridization of arrays. In general, it is inappropriate to combine data sets without adjusting for batch effects. Methods have been proposed to filter batch effects from data, but these are often complicated and require large batch sizes ( > 25) to implement. Because the majority of microarray studies are conducted using much smaller sample sizes, existing methods are not sufficient. We propose parametric and non-parametric empirical Bayes frameworks for adjusting data for batch effects that is robust to outliers in small sample sizes and performs comparable to existing methods for large samples. We illustrate our methods using two example data sets and show that our methods are justifiable, easy to apply, and useful in practice. Software for our method is freely available at: http://biosun1.harvard.edu/complab/batch/.

Bayes Theorem↗

PubMed2006

Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging.

Oxidative stress is implicated in atherogenesis, yet most clinical trials with antioxidants, particularly vitamin E, have failed to protect against atherosclerotic diseases. A striking exception is probucol, which retards atherosclerosis in carotid arteries and restenosis of coronary arteries after angioplasty. Because probucol has in vitro cellular-protective effects independent of inhibiting lipid oxidation, we investigated the mode of action of probucol in vivo. We used three models of vascular disease: apolipoprotein E-deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model of restenosis; and carotid injury in obese Zucker rats, a model of type 2 diabetes. Unexpectedly, we observed that the phenol moieties of probucol were insufficient, whereas its sulphur atoms were required for protection. Probucol and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue, protected via cell-specific effects on inhibiting macrophage accumulation, stimulating reendothelialization, and inhibiting vascular smooth muscle cell proliferation. These processes were mediated via induction of heme oxygenase-1 (HO-1), an activity not shared by vitamin E. Our findings identify HO-1 as the molecular target of probucol. They indicate 2-electron rather than radical (1-electron) oxidants as important contributors to atherogenesis, and point to novel lead compounds for therapeutic intervention against atherosclerotic diseases.

Animals↗

PubMed2006

Utilization of a whole genome SNP panel for efficient genetic mapping in the mouse.

Phenotype-driven genetics can be used to create mouse models of human disease and birth defects. However, the utility of these mutant models is limited without identification of the causal gene. To facilitate genetic mapping, we developed a fixed single nucleotide polymorphism (SNP) panel of 394 SNPs as an alternative to analyses using simple sequence length polymorphism (SSLP) marker mapping. With the SNP panel, chromosomal locations for 22 monogenic mutants were identified. The average number of affected progeny genotyped for mapped monogenic mutations is nine. Map locations for several mutants have been obtained with as few as four affected progeny. The average size of genetic intervals obtained for these mutants is 43 Mb, with a range of 17-83 Mb. Thus, our SNP panel allows for identification of moderate resolution map position with small numbers of mice in a high-throughput manner. Importantly, the panel is suitable for mapping crosses from many inbred and wild-derived inbred strain combinations. The chromosomal localizations obtained with the SNP panel allow one to quickly distinguish between potentially novel loci or remutations in known genes, and facilitates fine mapping and positional cloning. By using this approach, we identified DNA sequence changes in two ethylnitrosourea-induced mutants.

Animals↗

PubMed2006

BAL1 and BBAP are regulated by a gamma interferon-responsive bidirectional promoter and are overexpressed in diffuse large B-cell lymphomas with a prominent inflammatory infiltrate.

BAL1 is a transcription modulator that is overexpressed in chemoresistant, diffuse large B-cell lymphomas (DLBCLs). BAL1 complexes with a recently described DELTEX family member termed BBAP. Herein, we characterized BAL1 and BBAP expression in primary DLBCL subtypes defined by their comprehensive transcriptional profiles. BAL1 and BBAP were most abundant in lymphomas with a brisk host inflammatory response, designated host response (HR) tumors. Although these DLBCLs include significant numbers of tumor-infiltrating lymphocytes and interdigitating dendritic cells, BAL1 and BBAP were expressed primarily by malignant B cells, prompting speculation that the genes might be induced by host-derived inflammatory mediators such as gamma interferon (IFN-gamma). In fact, IFN-gamma induced BAL1 and BBAP expression in DLBCL cell lines; doxycycline-induced BAL1 also increased the expression of multiple IFN-stimulated genes, directly implicating BAL1 in an IFN signaling pathway. We show that BAL1 and BBAP are located on chromosome 3q21 in a head-to-head orientation and are regulated by a IFN-gamma-responsive bidirectional promoter. BBAP regulates the subcellular localization of BAL1 by a dynamic shuttling mechanism, highlighting the functional requirement for coordinated BBAP and BAL1 expression. IFN-gamma-induced BAL1/BBAP expression contributes to the molecular signature of HR DLBCLs and highlights the interplay between the inflammatory infiltrate and malignant B cells in these tumors.

Base Sequence↗

PubMed2006

[Internal fixation with the supporting steel of AO femoral condyles for treatment of complicated distal femoral fractures].

OBJECTIVE: To explore the technique and clinical effects of internal fixation of complicated distal femoral fractures using the supporting steel of AO femoral condyles. METHODS: From October 2001 to February 2004, 23 cases of complicated distal femoral fractures were treated with open reduction and internal fixation using the supporting steel of AO femoral condyles. Of 23 cases, there were 19 males and 4 females, aged 27-55 years. The locations were the right side in 10 cases and the left side in 13 cases. Fracture caused by traffic accident in 16 and by fall in 7, including 14 closed fracture and 9 open fracture, 21 fresh fracture and 2 old fracture. According to AO classification, 6 cases were classified as type A extra-articular fracture and 17 cases as type C intra-articular fracture. The X-ray films before operation showed comminuted fracture of femoral intercondylar and femoral supracondylar. All cases received scientific and rational rehabilitative treatment post-operatively. RESULTS: The postoperative follow-up ranged from 6 months to 20 months, 23 cases achieved fracture healing with an average healing period of 10.3 months (from 7 months to 16 months). According to the criteria of Kolmer and Wulff, the results were excellent in 16 cases, good in 4 cases, fair in 2 case and poor in 1 case. The excellent and good rate was 86.9%. CONCLUSION: Internal fixation with the supporting steel of AO femoral condyles for treatment of complicated distal femoral fractures has advantages of reasonable design, convenient operation, firm fixation and reliable clinical outcome.

Adult↗

PubMed2005

The PSEA promoter element of the Drosophila U1 snRNA gene is sufficient to bring DmSNAPc into contact with 20 base pairs of downstream DNA.

Most of the major spliceosomal small nuclear RNAs (snRNAs) (i.e. U1, U2, U4 and U5) are synthesized by RNA polymerase II (pol II). In Drosophila melanogaster, the 5'-flanking DNA of these genes contains two conserved elements: the proximal sequence element A (PSEA) and the proximal sequence element B (PSEB). The PSEA is essential for transcription and is recognized by DmSNAPc, a multi-subunit protein complex. Previous site-specific protein-DNA photo-cross-linking assays demonstrated that one of the subunits of DmSNAPc, DmSNAP43, remains in close contact with the DNA for 20 bp beyond the 3' end of the PSEA, a region that contains the PSEB. The current work demonstrates that mutation of the PSEB does not abolish the cross-linking of DmSNAP43 to the PSEB. Thus the U1 PSEA alone is capable of bringing DmSNAP43 into close contact with this downstream DNA. However, mutation of the PSEB perturbs the cross-linking pattern. In concordance with these findings, PSEB mutations result in a 2- to 4-fold reduction in U1 promoter activity when assayed by transient transfection.

Animals↗

PubMed2005

Allele-specific amplification in cancer revealed by SNP array analysis.

Amplification, deletion, and loss of heterozygosity of genomic DNA are hallmarks of cancer. In recent years a variety of studies have emerged measuring total chromosomal copy number at increasingly high resolution. Similarly, loss-of-heterozygosity events have been finely mapped using high-throughput genotyping technologies. We have developed a probe-level allele-specific quantitation procedure that extracts both copy number and allelotype information from single nucleotide polymorphism (SNP) array data to arrive at allele-specific copy number across the genome. Our approach applies an expectation-maximization algorithm to a model derived from a novel classification of SNP array probes. This method is the first to our knowledge that is able to (a) determine the generalized genotype of aberrant samples at each SNP site (e.g., CCCCT at an amplified site), and (b) infer the copy number of each parental chromosome across the genome. With this method, we are able to determine not just where amplifications and deletions occur, but also the haplotype of the region being amplified or deleted. The merit of our model and general approach is demonstrated by very precise genotyping of normal samples, and our allele-specific copy number inferences are validated using PCR experiments. Applying our method to a collection of lung cancer samples, we are able to conclude that amplification is essentially monoallelic, as would be expected under the mechanisms currently believed responsible for gene amplification. This suggests that a specific parental chromosome may be targeted for amplification, whether because of germ line or somatic variation. An R software package containing the methods described in this paper is freely available at http://genome.dfci.harvard.edu/~tlaframb/PLASQ.

Alleles↗

PubMed2005

Transverse load and orientation measurement with multicore fiber Bragg gratings.

We demonstrate the sensitivity of Bragg gratings in a multicore fiber to transverse load. The Bragg peaks are split because of stress-induced birefringence, the magnitude of which depends upon the load and grating position relative to the load axis. Experiments show that a set of gratings in a four-core fiber can measure a load axis angle to +/- 5 degrees and a load magnitude to +/- 15 N m(-1) up to 2500 N m(-1). We consider alternative designs of multicore fiber for optimal load sensing and compare experimental and modeled data.

Journal Article↗