Biology subjects

Chen, Y.-P.

Publications and source records attributed to Chen, Y.-P..

16 recordsLinked to original sources

bioRxiv2026

Genetic accessibility, not superior fitness, determines which anti-HBs antibody escape variants are selected in patients

Background and Aims: Genetic diversity within the hepatitis B virus (HBV) surface antigen (HBsAg) drives the emergence of immune escape variants, but studying this diversity in vivo has been limited by the difficulty of establishing infection from patient isolates. We aimed to perform unbiased in vivo screening of variants in the HBs antigenic loop for antibody escape and fitness, using synthetic DNA launch of HBV in human hepatocyte chimeric mice. Approach and Results: Direct intrahepatic injection (IHI) of barcoded, recombinant cccDNA established infection from up to 32,000 independent launch events of a genotype A strain and successfully launched clinical consensus sequences across the major genotypes. Using IHI, we performed deep mutational scanning of 4,608 codon variants across the HBs antigenic loop. Under control antibody treatment, diverse variants expanded, revealing differences in variant fitness in the absence of adaptive immune pressure. Anti-HBs monoclonal antibody treatment suppressed wild-type viremia while permitting breakthrough of resistant variants from the library. Sequencing identified strong enrichment for substitutions at G145 (G145Q, G145H, G145R). Notably, G145Q, rather than the clinically dominant G145R, showed the greatest fitness advantage, indicating that G145R's clinical prevalence does not reflect superior intrinsic fitness. Conclusions: Unbiased in vivo screening reveals that clinically observed HBV escape mutations reflect which substitutions are genetically accessible by single nucleotide change and compatible with the overlapping polymerase reading frame, rather than which confer optimal fitness. This approach establishes a platform for high-resolution mapping of viral variant fitness under antiviral selection pressure.

microbiology↗

bioRxiv2025

Antimetastatic Sulfonate-Functionalized Mesoporous Silica Nanoparticles Enhance Irinotecan Stability and Delivery for Colorectal Cancer Treatment

Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality, with Irinotecan (IRI) serving as a backbone chemotherapeutic despite its dose-limiting toxicities, instability of the active lactone form, and lack of intrinsic antimetastatic activity. To overcome these barriers, we developed sulfonate-functionalized mesoporous silica nanoparticles (MSNs), referred to as (SO3-)-MSN-PEG/TA, as a multifunctional nanocarrier for IRI delivery. This nanoformulation markedly enhanced drug loading efficiency and preserved over 90% of the lactone form for up to six months, enabling sustained release and improved pharmacological stability. In vitro studies demonstrated superior cellular uptake, enhanced apoptosis, and a reduced IC50 compared to free IRI. Beyond drug delivery, (SO3-)-MSN-PEG/TA exhibited intrinsic antimetastatic activity by modulating focal adhesion kinase (FAK)/paxillin signaling, thereby impairing cell migration and suppressing angiogenesis, along with efficient tumor accumulation through the enhanced permeability and retention (EPR) effect. Pharmacokinetic analysis further revealed that IRI@(SO3-)-MSN-PEG/TA prolonged systemic retention, maintaining higher IRI plasma concentrations compared with free IRI. IRI@(SO3-)-MSN-PEG/TA significantly inhibited both primary tumor growth and metastatic dissemination in orthotopic and heterotopic colorectal cancer models, while markedly reducing systemic toxicities and preserving bone marrow cellularity relative to free IRI and liposomal IRI (Onivyde). Collectively, this dual-functional nanomedicine provides an innovative therapeutic strategy that not only augments IRI efficacy but also confers metastasis suppression and favorable pharmacokinetics, addressing critical unmet needs in mCRC treatment. These findings highlight the translational potential of IRI@(SO3-)-MSN-PEG/TA as a safer and more effective therapy for mCRC.

bioengineering↗

bioRxiv2025

Microbial community characteristics and stable relationships centered on anammox bacteria revealed by global-scale analysis

Anaerobic ammonium-oxidizing bacteria (AnAOB) play important roles in both artificial wastewater treatment systems and natural ecosystems. To date, AnAOB pure cultures are not available and they tend to coexist with various microbial species. However, anammox community characteristics including the relationships between AnAOB and their companion bacteria at the global perspective and their impacts on anammox metabolism remain unclear. Here, we systematically analyzed the characteristics of anammox communities and the stable relationships concerning AnAOB using a global dataset containing 619 anammox-related amplicons. Different anammox systems showed significant differences in alpha and beta diversity, but shared some core taxa of interest. A total of 89 and 55 core genera and species were identified respectively across anammox communities worldwide, which formed the backbone of artificial anammox systems. Through the analysis of co-abundance networks derived from four distinct artificial anammox systems--biofilm, granular sludge, flocculent sludge, and planktonic cells--we identified 208 stable and 92 limited stable relationships associated with AnAOB. Functional analysis suggested that stable positively-correlated companion bacteria may provide essential cofactors (e.g., molybdenum cofactor, tetrahydrofolate, and coenzyme A) to AnAOB. The companion bacteria which showed limited stable positive correlations with AnAOB in the anammox attachment-growth systems, may mutualize with AnAOB via type pili. This study deepens the understanding of anammox communities, anammox core microbiome, and AnAOB symbiotic relationships. These (limited) stable companion bacteria and corresponding cofactors can potentially guide the development and application of bioaugmentation methods, synthetic anammox communities, and deterioration biomarkers for engineered anammox systems.

microbiology↗

bioRxiv2024

Rapid radiation of a plant lineage sheds light on the assembly of dry valley biomes

Southwest China is characterized by high plateaus, large mountain systems, and deeply incised dry valleys formed by major rivers and their tributaries. Despite the considerable attention given to alpine plant radiations in this region, the timing and mode of the diversification of the numerous plant lineages in the dry valley habitat remains unknown. To address this knowledge gap, we investigate the macroevolution of Isodon (Lamiaceae), a lineage commonly distributed in the dry valleys in southwest China and wetter areas of Asia and Africa. We reconstructed a robust phylogeny encompassing nearly 90% of the approximately 140 extant Isodon species using transcriptome and genome-resequencing data. Our results suggest a rapid radiation of Isodon during the Pliocene that coincided with a habit shift from herbs to shrubs and a habitat shift from humid areas to dry valleys. The shrubby growth form likely acted as a preadaptation allowing for the movement of Isodon species into these valleys. Ecological analysis highlighted aridity and precipitation as key factors influencing the niche preferences of different growth forms and species richness of Isodon. Integrating our results with insights from tectonic movements in the Tibetan Plateau and adjacent regions, we infer that the interplay between topography and the evolution of the East Asian monsoon since the middle Miocene likely contributed to the formation of the dry valley biome in southwest China. This study enhances our understanding of evolutionary dynamics and ecological drivers shaping the distinctive flora of this region.

evolutionary biology↗

bioRxiv2023

Complete genome-centric analysis reveals functional divergence and adaptive evolution of uncultured bacteria in anammox community

Anaerobic ammonium-oxidation (anammox) bacteria play a crucial role in global nitrogen cycling and wastewater nitrogen removal, but they share symbiotic relationships with various other microorganisms. No pure culture is available for anammox bacteria so far. Although shotgun metagenomics based on short reads has been widely used in anammox research, metagenome-assembled genomes (MAGs) are often discontinuous and highly contaminated, which limits in-depth analyses of anammox communities. Here, for the first time, we performed Pacific Biosciences high-fidelity (HiFi) long-read sequencing on the anammox granule sludge sample from a lab-scale bioreactor, and obtained 30 accurate and complete metagenome-assembled genomes (cMAGs). These cMAGs were obtained by selecting high-quality circular contigs from initial assemblies of long reads generated by HiFi sequencing, eliminating the need for Illumina short reads, binning, and reassembly. One new anammox species and species from three novel families were found in this anammox community. cMAG-centric analysis revealed divergences in general and nitrogen metabolism among members of the anammox community. Furthermore, we identified mobile genetic elements (MGEs) and putative horizontal gene transfer (HGT) events within these cMAGs to explore the adaptive evolution of the community. The results suggest that MGEs and HGT events, particularly transposons containing tnpA in anammox bacteria, might play important roles in the adaptive evolution of this anammox community. The cMAGs generated in the present study could be used to establish of a comprehensive database for anammox bacteria and associated microorganisms. Our findings highlight the advantages of HiFi sequencing for the studies of complex mixed cultures such as anammox communities and advance our understanding of anammox communities.

microbiology↗

bioRxiv2022

Speech intelligibility changes the temporal evolution of neural speech tracking

Listening to speech with poor signal quality is challenging. Neural speech tracking of degraded speech has been used to advance the understanding of how brain processes and speech intelligibility are interrelated, however the temporal dynamics of neural speech tracking are not clear. In the present MEG study, we thereby exploited temporal response functions (TRFs) and generated signal-degraded speech to depict the temporal evolution of speech intelligibility modulation on neural speech tracking. In addition, we inter-related facets of neural speech tracking (e.g., speech envelope reconstruction, speech-brain coherence, and components of broadband coherence spectra) to endorse our findings in TRFs. Our TRF analysis yielded marked temporally differential effects of vocoding: reduction of intelligibility went along with large increases of early peak responses ([~]50-110 ms, M50TRF), but strongly reduced responses around 175-230 ms (M200TRF). For the late responses 315-380 ms (M350TRF), the maximum response occurred for degraded speech that was still comprehensible then declined with reduced intelligibility. Furthermore, we related the TRF components to our other neural "tracking" measures and found that M50TRF and M200TRF play a differential role in the shifting center frequency of the broadband coherence spectra. Overall, our study highlights the importance of time-resolved computation and parametrization of coherence spectra on neural speech tracking and provides a better understanding of degraded speech processing. HighlightsO_LIWe use MEG to show that speech intelligibility differentially impacts the temporal evolution of neural speech tracking. C_LIO_LITRF responses around 200 ms show the strongest relationship with behaviour. C_LIO_LIRelating TRF effects to parameterized coherence spectra using FOOOF suggests that M50TRF and M200TRF reflect shifts in which speech features are tracked over time. C_LI

neuroscience↗

bioRxiv2021

Neural speech tracking shifts from the syllabic to the modulation rate of speech as intelligibility decreases

The most prominent acoustic features in speech are intensity modulations, represented by the amplitude envelope of speech. Synchronization of neural activity with these modulations is vital for speech comprehension. As the acoustic modulation of speech is related to the production of syllables, investigations of neural speech tracking rarely distinguish between lower-level acoustic (envelope modulation) and higher-level linguistic (syllable rate) information. Here we manipulated speech intelligibility using noise-vocoded speech and investigated the spectral dynamics of neural speech processing, across two studies at cortical and subcortical levels of the auditory hierarchy, using magnetoencephalography. Overall, cortical regions mostly track the syllable rate, whereas subcortical regions track the acoustic envelope. Furthermore, with less intelligible speech, tracking of the modulation rate becomes more dominant. Our study highlights the importance of distinguishing between envelope modulation and syllable rate and provides novel possibilities to better understand differences between auditory processing and speech/language processing disorders. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/437033v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@6364adorg.highwire.dtl.DTLVardef@166daaeorg.highwire.dtl.DTLVardef@19eedd2org.highwire.dtl.DTLVardef@10f7aed_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

Quantitative three-dimensional nondestructive imaging of whole anaerobic ammonium-oxidizing bacteria

Anaerobic ammonium-oxidizing (anammox) bacteria play a key role in the global nitrogen cycle and the treatment of nitrogenous wastewater. These functions are closely related to the unique biophysical structure of anammox bacteria. However, the research on the biophysical ultrastructure of intact anammox bacteria is lacking. In this study, in-situ three-dimensional nondestructive ultrastructure imaging of whole anammox cell was performed using synchrotron soft X-ray nano-computed tomography and the total variation-based simultaneous algebraic reconstruction technique (TV-SART). Statistical and quantitative analyses of the ultrastructures of intact anammox bacteria were performed. The linear absorption coefficient values of the ultrastructures of anammox bacteria were calculated and the asymmetric structure of the anammox bacteria was quantified. On this basis, the shape adaptation of the anammox bacteria responses to Fe2+ were explored, and the underlying regulation mechanism of Fe2+ on anammox bacteria was explored. Furthermore, a promising method to study the biophysical properties of cells in different environments and engineering processes was proposed.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC=\"FIGDIR/small/709188v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (23K):\norg.highwire.dtl.DTLVardef@1994e5eorg.highwire.dtl.DTLVardef@1e80137org.highwire.dtl.DTLVardef@a7f418org.highwire.dtl.DTLVardef@8a77e5_HPS_FORMAT_FIGEXP M_FIG C_FIG Statement of SignificanceAnaerobic ammonium-oxidizing (anammox) bacteria play key role in global nitrogen cycle, and this physiological function depends on the unique morphology of anammox bacteria. In this study, synchrotron soft-X ray imaging technique coupled with simultaneous algebraic reconstruction technique with total variation (SART-TV) algorithm were performed to quantify the three-dimensional ultrastructure of the whole anammox bacteria for the first time. On this basis, the shape adaptation and mechanism of the anammox bacteria responses to Fe2+ were explored and a promising method for detecting the physiological properties of anammox bacteria was proposed.

cell biology↗

bioRxiv2019

Sinoseris (Crepidinae, Cichorieae, Asteraceae), a new genus endemic to China of three species, two of them new to science

Elucidating the systematic position of two Chinese species described originally as Lactuca hirsuta and L. scandens, of which only historical specimens from the late 19th and early 20th century were known, field work confirmed the occurrence of three different species. Molecular phylogenetic analysis of these species based on sequences of the nuclear ribosomal internal transcribed spacer (nrITS) region uncovered a hitherto unknown lineage in a phylogenetic backbone of the subtribe Crepidinae of the sunflower family tribe Cichorieae. Substantiated by comparative morphological studies, this lineage is described as genus new to science, named Sinoseris, endemic to the Chinese provinces Sichuan and Yunnan. Two of its three species are new to science, while the third is conspecific with both L. hirsuta and L. scandens.

plant biology↗

bioRxiv2018

Dietary sulfate-driven and gut dysbiosis-triggered breast cancer-related gene upregulation

By gut microbiota metagenomic analysis, we found that the abundance of sulfatase-secreting bacteria (SSB) in the gut of mice fed chondroitin sulfate (CS) increases with significant individual difference. The fluctuation of lipopolysaccharide (LPS) and pro-inflammatory indicators with significant individual and tissue variations was also observed. After mice were fed mixed with CS or injected separately with LPS, the breast cancer-related transcriptional factor genes, BCL11A and RUNX1, were upregulated, whereas the tumor suppressor gene, TP53BP1, were downregulated. Further, the mammary myopithelium marker CK5/6, the mammary hyperplasia marker Ki-67, and other tumor markers were also upregulated. While the exogenous estradiol does not induce the expression of BCL11A, RUNX1, and TP53BP1, the estrogen receptor (ER) agonist Fulvestrant that mimics estradiol action not only elevates estradiol concentrations, but also upregulates tumor marker expression levels, revealing that ER inflammatory inactivation and hyperestrogenemia induction might be the etiological cues of breast cancer origin. This study has preliminarily established a possible correlation of gut microbiota dysbiosis and chronic low-grade inflammation with the early-phase onset of breast cancer in mice. The statistical insignificance of test data was attributed to the individual difference of gut microbiota compositions, which determining the individual and tissue variations of systemic inflammation.

cancer biology↗

bioRxiv2018

Spring mineral water-borne bacteria reshape gut microbiota profiles and confer health benefits

BackgroundAlthough dietary patterns are recognized to affect health by interfering with gut microbiota homeostasis, whether live or dead bacteria-bearing spring mineral water (MW) would also exert beneficial effects on health upon curing gut dysbiosis remains unknown.\n\nResultsDue to harboring live bacteria, the heated but unboiled MW from Bama, where centenarians are ubiquitously inhabited, reshapes the gut microbiota from a traveler-type to a local resident-type except for Prevotella. While chondroitin sulfate, a component occurring in livestock and poultry meats, increases the richness of sulfatase-secreting bacteria and sulfate-reducing bacteria, Bama MW dampens the overgrowth of those colon-thinning bacteria and hampers the overexpression of multiple genes responsible for anti-inflammation, anti-oxidation, anti-hypoxia, anti-mutagenesis, and anti-tumorigenesis.\n\nConclusionsBama spring MW prevents the early-phase onset of breast cancer by curating gut dysbiosis. MW also compromises chromosomal DNA damage and ameliorate mitochondrial dysfunctions, implying it may extend lifespan.

microbiology↗

bioRxiv2018

Short-hairpin RNA-guided single gene knockdown reverses triple-negative breast cancer

BackgroundThe origin of breast cancer remains poorly understood. Here, we testify a putative mechanism of \"breast cancer origin from inducible nitric oxide synthase (iNOS) activation and oestrogen receptor alpha (ER) inactivation\", which are classified as the essential outcomes of chronic inflammatory responses.\n\nMethodsTo reverse breast cancer status, iNOS was downregulated by short-hairpin RNA (shRNA)-guided NOS2 knockdown from human triple-negative breast cancer (TNBC) cells. To re-enact breast cancer origin, ER was downregulated by shRNA-directed ESR1 knockdown in human mammary epithelial cells.\n\nResultsUpon NOS2 knockdown from HCC1937 cells, the specific TNBC transcription factor genes, RUNX1 and BCL11A, were downregulated, hypoxia was compromised, Warburg effects were attenuated, and tumourigenic proliferation was halted, accompanied by an increase in the tumour marker cyclin D1 (CD1) and a decrease in the tumour suppressor cyclin-dependent kinase inhibitor (CKI). In contrast, ESR1 knockdown from MCF-10A cells led to upregulated BCL11A and RUNX1 expression, augmented hypoxic responses, pronounced Warburg effects, and enhanced PI3K/Akt/mTOR signalling, together with low levels of CD1 and high levels of CKI induction.\n\nConclusionsBreast cancer should originate from inflammatory signalling, during which iNOS activation and ER inactivation elicit hypoxia, oxidation, mitochondrial dysfunction, and breast cancer-like hyperplasia, demonstrating that iNOS inhibitors and ER activators represent promising candidate prodrugs enabling breast cancer prevention in the early stage.

cancer biology↗

bioRxiv2017

Insulin Does Not Augment In Vitro Tumor Growth Under A Hyperglycemia-Mimicking Milieu And In A Calorie Restriction-Resembling Manner

BackgroundWhether insulin enhances or represses tumor cell proliferation remains debating and inconclusive although epidemiological data indicated insulin use raises a risk of cancer incidence in patients with diabetes mellitus (DM).\n\nMethodology/Principle FindingsWe cultured rat pituitary adenoma cells in a high-glucose medium to simulate hyperglycemia occurring in DM patients. Upon incubation with or without insulin, repressed tumor cell proliferation and downregulated tumor marker expression occur accompanying with mitigated oxidative stress and compromised apoptosis. Mechanistically, insulin resistance-abrogated glucose uptake was suggested to create an intracellular low-glucose milieu, leading to cellular starvation resembling calorie restriction (CR). While downregulation of insulin-like growth factor 1 (IGF-1) occurring in CR was validated, oncogene downregulation and tumor suppressor gene upregulation seen in CR was also replicated by NOS2 knockdown.\n\nConclusions/SignificanceCellular starvation can exert CR-like anti-tumor effects regardless of insulin presence or absence.

cancer biology↗

bioRxiv2017

Artemisinin mimics nitric oxide to reduce adipose weight by targeting mitochondrial complexes

It remains obscure how to medically manage visceral obesity that predisposes metabolic disorders. Here, we show for the first time that a trace amount of artemisinin (0.25 mg/kg) reduces adipose weight in an inflammatory obese mouse model induced by a high-fat diet with lipopolysaccharide (HFD+LPS). HFD+LPS trigger pro-inflammatory responses, upregulate NOS2 expression, elicit potent nitric oxide (NO) burst, and reinforce adipose mitochondrial dysfunctions that facilitate adipogenesis for visceral weight gain. By targeting mitochondrial complexes, artemisinin resembles the NO donor nitroglycerin to exert anti-inflammatory effects, downregulate NOS2 expression, maintain stable NO release, and augment adipose mitochondrial functions that necessitate adipolysis for visceral weight loss. Taken together, artemisinin plays adipose weight-reducing roles by rectifying inflammation-driven mitochondrial dysfunctions.

pharmacology and toxicology↗

bioRxiv2017

Chondroitin Sulfate Flourishes Gut Sulfatase-Secreting Bacteria To Damage Mucus Layers, Leak Bacterial Debris, And Trigger Inflammatory Lesions In Mice

BackgroundAn interaction of the food types with the gut microbiota changes is deeply implicated in human health and disease. To verify whether animal-based diets would lead to gut dysbiosis, systemic inflammation and inflammatory pathogenesis, we fed mice with chondroitin sulfate (CS), a sulfate-containing O-glycan naturally occurring in livestock and poultry products, and monitored the dynamic changes of microbial flores, inflammatory signatures, and pathogenic hallmarks.\n\nResultsA metagenomic gut microbiota analysis revealed the overgrowth of sulfatase-secreting bacteria and sulfate-reducing bacteria in the gastrointestinal tracts of mice upon daily CS feeding. Sulfatase-secreting bacteria compromise gut integrity through prompting mucin degradation and mucus lesions, which were evident from the upregulation of secretary leukocyte protease inhibitor (SLPI) and mucin 1/4 (MUC-1/4). A synchronous elevation of lipopolysaccharide (LPS) and tumor necrosis factor (TNF-) levels in the serum as well as cerebral, hepatic, cardiac and muscular tissues suggests bacterial endotoxinemia, chronic low-grade inflammation and mitochondrial dysfunction, eventually leading to the onset of global inflammatory pathogenesis towards arthritis, dementia, tumor, and fatty liver.\n\nConclusionsCS triggers the early-phase and multi-systemic pathogenesis like arthritis, dementia, tumor, and fatty liver by enhancing gut opportunistic infection and evoking low-grade inflammation in mice. A plausible reason for the inconsistency of CS in treatment of osteoarthritis (OA) was also discussed.

pathology↗

bioRxiv2017

Chondroitin sulfate elicits systemic pathogenesis in mice by interfering with gut microbiota homeostasis

Whether chondroitin sulfate (CS), a common ingredient naturally occurring in livestock and poultry products, improves osteoarthritis remains debating. Here, we show for the first time that CS induces steatogenesis, atherogenesis, and dementia-like pathogenesis in mice. Gut microbiome analysis revealed the sulfatase-secreting bacteria Rikenella and the sulfate-reducing bacteria Desulfovibrio are enriched. Surprisingly, berberine use boosts CS-induced multi-loci inflammatory manifestations by further increasing the abundance of Rikenella and Desulfovibrio, whereas cephalosporin reinforces the colon mucus barrier via flourishing Akkermansia muciniphila and upregulating mucin expression. Mechanistically, berberine aggravates mucus lining injury by prompting mucin degradation, endotoxin leakage, neutralizing antibody induction, pro-inflammatory cytokine burst, lactic acid accumulation and energy currency depletion in multiple organs and tissues. Taken together, CS evokes the early-phase pathogenesis toward steatohepatitis, atherosclerosis, and dementia upon augmenting gut opportunistic infection, and a sustained antibiotic monotherapy does not deprive the risk of CS-driven systemic inflammatory disorders.

pharmacology and toxicology↗