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Biology subjects

Sheng, W.

Publications and source records attributed to Sheng, W..

18 recordsLinked to original sources

Asymmetric introgression and thermal advantage jointly drive climate-mediated lineage turnover in a mixed-ploidy reed

Species distribution forecasts commonly overlook intraspecific genetic variation, missing a potentially important mechanism of ecosystem change: climate-driven range shifts among lineages within a species native range. Here we integrate population genomic analysis of 495 individuals, multi-site common garden experiments, and species distribution modeling based on 837 occurrence records for three major genetic lineages of the foundation grass Phragmites australis in China. The octoploid FEAU lineage (haplotype P) exhibits superior heat tolerance (critical temperature Tcrit and T50) and produces significantly greater total biomass in three of four common gardens compared to the cold-adapted CN lineage (tetraploid, haplotypes O/M), which occupies a climatic niche with lower annual mean temperature (Bio1) and mean temperature of the wettest quarter (Bio8). Genomic analyses further reveal bidirectional but asymmetric introgression, with admixed individuals showing a systematic bias toward FEAU ancestry. Under the high-emission scenario (SSP5-8.5) by 2070, projected highly suitable habitat for the FEAU lineage expands by 18.6%, while the CN lineage shows a smaller relative increase. By contrast, the subtropical SW lineage (haplotypes U/I) exhibits limited and stable suitable habitat. These results demonstrate that climate change interacts with intraspecific variation among polyploidy-associated lineages, manifested through differences in thermal tolerance, biomass production, and asymmetric gene flow, to drive potential lineage replacement within a native range, a process already suggested by field observations of FEAU expansion in a plateau lake. Our findings argue for integrating evolutionary history and genetic identity into ecological forecasting to better anticipate ecosystem responses under ongoing climate warming.

ecology↗

Genetic canalization of nutrient resorption: evidence from a widespread grass under effective salt stress

Nutrient resorption is a key plant strategy for nutrient conservation, yet whether it responds plastically to non-nutrient stressors such as salinity remains unresolved. Using a common garden experiment with 110 genotypes of the cosmopolitan grass Phragmites australis, we first established that the imposed salinity treatment induced strong multi-level stress responses: above-ground biomass declined by >60%, sodium accumulated 3- to 5-fold across all leaf stages, and 484 metabolites showed significant differential accumulation, including canonical markers of osmotic and oxidative stress. Against this backdrop of confirmed stress, we found that nutrient resorption efficiency (NuRE) remained largely unaffected by salinity. Instead, NuRE was strongly correlated with phylogeographic lineage, ecotype, and latitude of origin, demonstrating evolutionary canalization rather than short-term acclimation. Element-specific regulatory patterns were also evident: while phosphorus resorption followed concentration-dependent control regardless of stress, nitrogen control was disrupted under salinity, and potassium resorption showed no such dependence. Our findings reveal that intraspecific variation in nutrient resorption is predominantly shaped by historical adaptation and geographic context, not by plasticity to salinity. This genetic canalization of a key functional trait implies that predictions of nutrient cycling under global change must account for the phylogeographic composition of plant populations.

ecology↗

Decoding the fibroblast/mast cell signaling pathway of acupuncture

Acupuncture has been practiced for thousands of years with documented therapeutic effects, yet its underlying biological mechanisms remain poorly understood. Here, we show that acupuncture stimulation converts local mechanical forces into neuronal signals through defined cellular interactions, establishing a causal axis that links micro-level events at the ST36 acupoint to systemic therapeutic effects. We demonstrate that acupuncture needle manipulation transmits mechanical tension through collagen fibers to local fibroblasts, which subsequently secrete stem cell factor (SCF) and interleukin-33 (IL-33) in the acupoint. SCF recruits mast cells, while IL-33 induces their activation and the release of neuromodulatory molecules. These molecules then engage the nervous system, as evidenced by c-fos expression in the lumbar dorsal horn, demonstrating the transmission of acupuncture-induced peripheral signals into central circuits. Together, these findings define a functional axis linking needle-evoked stimulation to neuronal activation and provide a mechanistic framework for understanding the biological basis of acupuncture and for its evidence-based refinement.

cell biology↗

Diammonium glycyrrhizinate injection promotes zebrafish angiogenesis through the mTOR/HIF-1 signaling pathway

(1) BackgroundGlycyrrhizic acid (GA) is the main component of the traditional Chinese medicine Glycyrrhiza glabra. Many GA preparations in the pharmaceutical market have good efficacy in hepatoprotection and the treatment of liver diseases. However, the pro-angiogenic effects for GA-based agents have not been researched specifically. The aim of this study was to investigate the pro-angiogenic activity of GA preparations commonly used in clinical practice and screen the representative angiogenesis promotor to further elucidate the mechanism of action (2) MethodsA zebrafish vascular injury model induced by PTK787 was used to assess the pro-angiogenic effect of GA preparations. The pro-angiogenic activity of diammonium glycyrrhizinate injection (DGI) was further systematically evaluated by detecting the growth of the intersegmental vessels (ISVs) and subintestinal vein vessels (SIVs) in zebrafish. The underlying mechanism of action for DGI was explored by transcriptomics analysis and RT-qPCR validation; (3) ResultsThe results showed that magnesium isoglycyrrhizinate injection (MII), DGI, compound glycyrrhizinate tablets (CGT), and diammonium glycyrrhizinate enteric-coated capsules (DGEC) could demonstrate significantly pro-angiogenic effects. Among them, DGI exhibited the strongest activity. Transcriptomic analysis showed that the pro-angiogenic activity of DGI was closely associated with the mTOR signaling pathway. RT-qPCR results indicated that the expression levels of key genes of the mTOR/HIF- pathway were significantly upregulated in DGI-treated zebrafish relative to the PTK787 group; (4) ConclusionsGA preparations have an obvious pro-angiogenic effect, in which DGI can exert particularly strong activity by activating the mTOR/HIF-1 signaling pathway. This study broadens the clinical application of GA agents and provides new insights into the pharmacodynamics and potential mechanisms of DGI as a candidate agent for treating ischemic diseases

pharmacology and toxicology↗

Plat safeguards maternally aged oocytes against programmed cell death through activating the Erk1/2 pathway

The decline in oocytes quality and developmental potential with female reproductive aging is well recognized, yet the underlying mechanisms remain insufficiently investigated. In this study, through an integrative analysis of transcriptomes and morphologies of individual oocytes from young and aged mice, morphologically defective aged oocytes are identified with distinct transcriptomic features. Further analysis demonstrates that both apoptotic and ferroptotic pathways are activated in the defective aged oocytes, and simultaneously blocking both pathways reverses the defective morphology to the largest extent. The Plat gene, which encodes tissue-type plasminogen activator (tPA), is downregulated with oocyte aging, and Plat knockdown increases oocytes susceptibility to both apoptosis and ferroptosis. Mechanistically, tPA functions as an upstream signaling molecule for Erk1/2 activation by interacting with particular phosphorylation kinases such as Alk. Consequently, Plat loss downregulates Erk1/2 pathway activity in oocytes, leading to degeneration through programmed cell death. Supplementing exogenous tPA in in vitro oocyte maturation cultures reduces defect rate of aged oocytes, thereby improving oocyte quality and developmental potential. Collectively, Plat plays a pivotal role in protecting aged mouse oocytes from programmed cell death, and tPA supplementation may serve as a potential clinical strategy to enhance oocyte quality in females of advanced maternal age.

developmental biology↗

Posterior parietal cortex mediates rarity-induced decision bias and learning under uncertainty

Optimal decision-making under uncertainty is critical for survival, yet real-world decisions often deviate from optimality. Here, we report a rarity-induced bias in humans and mice, where rare events exert a stronger and more persistent impact on future decisions than common events. Optogenetic manipulations demonstrate two opposing roles of the posterior parietal cortex (PPC): generating rarity-induced bias throughout learning, and driving optimal choices in the expert stage. In vivo recordings support both roles: preceding rare rewards enhance the activity of PPC neurons encoding the biased choice while suppressing neurons encoding the opposite choice, causing bias; learning enhances the stimulus-encoding capacity of PPC neurons, promoting optimal choices. A data-driven metacognitive model recapitulated the bias and learning process, and predicted PPCs causal role in learning, as validated by optogenetics. Our study uncovers an evolutionarily conserved rarity impact in decision-making, and elucidates essential roles of PPC in mediating rarity-induced bias and learning under uncertainty.

neuroscience↗

TvAP65 in Trichomonas vaginalis Promotes HPV Infection by Interacting with Host Molecules

Cervical cancer induced by human papillomavirus (HPV) infection poses a serious threat to womens health. Studies have shown that Trichomonas vaginalis (T. vaginalis), which is widely prevalent globally, can facilitate HPV infection. However, the underlying mechanism remains unclear. This study found that T. vaginalis significantly enhanced HPV infection in HaCaT cells and mouse vaginas through in vivo and in vitro experiments, and promoted the expression of HPV membrane receptor molecules CD151 and HSPG2. The HPV infection rate and CD151/HSPG2 expression levels were significantly decreased after reducing the expression of T. vaginalis adhesion protein 65 (TvAP65). In contrast, both HPV infection rates and CD151/HSPG2 expression were significantly increased in HaCaT cells over-expressing TvAP65. When both TvAP65 in T. vaginalis and CD151/HSPG2 in HaCaT cells were knocked down simultaneously, the infection rate of HPV in HaCaT cells was further reduced. These results suggest that TvAP65 promotes HPV infection by up-regulating the expression of CD151 and HSPG2. Furthermore, this study knocked down the 12 interacting molecules of TvAP65 in HaCaT cells one by one, and found that the HPV infection rate was significantly reduced after T. vaginalis infected HaCaT cells with low expression of FTH1, SPCS1, ATP5MC3, ITGB7, PMEPA1 or REEP5. Among them, SPCS1 played the most significant role. Simultaneous knockdown of TvAP65 and SPCS1 further significantly down-regulated the infection rate of HPV in HaCaT cells. Moreover, this molecule also down-regulated the promoting effect of T. vaginalis on HSPG2/CD151 expression. These results imply that SPCS1 plays an important role in T. vaginalis promoting HSPG2/CD151 expression and HPV infection. This study not only further proved that T. vaginalis can promote HPV infection but also explores the molecular mechanism by which TvAP65, through its interaction with SPCS1, up-regulates the expression of HSPG2 and CD151, thereby facilitating HPV infection. This provides a theoretical basis for clarifying the mechanism of co-infection between T. vaginalis and HPV.

microbiology↗

The ventral CA2 region of the hippocampus and its differential contributions to social memory and social aggression

Although it is well-known that the hippocampus mediates declarative memory (the repository of information of people, places, things and events) and influences behavior, the differential contributions of the dorsal and ventral hippocampus to specific forms of memory and behavior remain largely unknown. Studies to date show that the dorsal hippocampal CA1 region is important for cognitive and spatial tasks whereas the ventral CA1 region is associated with affective or emotional processing. Whether other regions and forms of hippocampal-dependent memory and behavior show a similar distinction remains unclear. Here we examine how social memory and related social behaviors are encoded across the dorso-ventral axis of the hippocampus. Although recent studies show that the dorsal hippocampal CA2 region is required for social memory and acts to promote social aggression, the behavioral role of ventral CA2 remains unknown. Indeed, whether a defined CA2 region extends throughout ventral hippocampus is controversial. Here, we report that a molecularly, anatomically and electrophysiologically defined CA2 region extends to the extreme ventral pole of hippocampus, with both similarities and important differences in its projection patterns and synaptic impact compared to dorsal CA2. Of particular importance, we find that ventral CA2 is not required for social memory but is critical for promoting social aggression. These results support the view that the ventral region of hippocampus is more generally tuned for emotionally-related behaviors compared to the cognitively-tuned dorsal hippocampus.

neuroscience↗

Contracted anterior-posterior systematic covariance of cortical thickness in early-onset schizophrenia

Background and HypothesisSchizophrenia is a neurodevelopmental condition with alterations in both sensory and association cortical areas. These alterations have been reported to follow structural connectivity patterning, and to occur in a system-level fashion. Here, we investigated whether pathological alterations of schizophrenia originated from an early disruption of cortical organization by using 7-17-years-old individuals with early-onset schizophrenia (EOS). Study DesignWe estimated cortical thickness using T1-weighted structural MRI data from 95 patients with antipsychotic-naive first-episode EOS and 99 typically developing (TD) controls. We then computed structural covariance of cortical thickness and estimated system-level organizational axes by performing nonlinear dimensionality reduction techniques on covariance matrices for the EOS and TD groups. Finally, we tested for group differences between EOS and TD individuals in terms of both structural covariance and covariance distances along the systematic axis. Study ResultsThe first covariance gradient differentiated motor regions from other cortical areas. Similar to the macrostructural axis in adults, the second gradient axis in young TD discriminated anterior from posterior regions and was compressed in EOS patients relative to TD controls. In addition, patients showed increased structural covariance between two ends of the systematic axis, with increased geodesic distance of covarying regions between two ends. ConclusionOur findings revealed a contracted organizational axis of cortical thickness in EOS patients, which was attributed to excessive distally coordinated changes between anterior and posterior regions of the cortex. Taken together, our study suggests a possible early disruption of system-level neurodevelopment in schizophrenia.

pathology↗

TAK1-mediated phosphorylation of PLCE1 represses PIP2 hydrolysis to impede esophageal squamous cancer metastasis

TAK1 is a serine/threonine protein kinase that is a key regulator in a wide variety of cellular processes. However, the functions and mechanisms involved in cancer metastasis are still not well understood. Here, we found that TAK1 knockdown promoted esophageal squamous cancer cell (ESCC) migration and invasion, whereas TAK1 overexpression resulted in the opposite outcome. These in vitro findings were recapitulated in vivo in a xenograft metastatic mouse model. Mechanistically, co-immunoprecipitation and mass spectrometry demonstrated that TAK1 interacted with phospholipase C epsilon 1 (PLCE1), and phosphorylated PLCE1 at serine 1060 (S1060). Functional studies revealed that phosphorylation at S1060 in PLCE1 resulted in decreased enzyme activity, leading to the repression of PIP2 hydrolysis. As a result, the degradation products of PIP2 including diacylglycerol (DAG) and inositol IP3 were reduced, which thereby suppressed signal transduction in the axis of PKC/GSK-3{beta}/{beta}-Catenin. Consequently, expression of cancer metastasis-related genes was impeded by TAK1. Overall, our data indicate that TAK1 plays a negative role in ESCC metastasis, which depends on the TAK1 induced phosphorylation of PLCE1 at S1060.

cancer biology↗

Neurodevelopmentally rooted epicenters in schizophrenia: sensorimotor-association spatial axis of cortical thickness alterations

Pathologic perturbations in schizophrenia have been suggested to propagate via the functional and structural connectome across the lifespan. Yet how the connectome guides early cortical reorganization of developing schizophrenia remains unknown. Here, we used early-onset schizophrenia (EOS) as a neurodevelopmental disease model to investigate putative early pathologic origins that propagate through the functional and structural connectome. We compared 95 patients with antipsychotic-naive first-episode EOS and 99 typically developing controls (7-17 years of age, 120 females). Whereas patients showed widespread cortical thickness reductions, thickness increases were observed in primary cortical areas. Using normative connectomics models, we found that epicenters of thickness reductions were situated in association regions linked to language, affective, and cognitive functions, while epicenters of increased thickness in EOS were located in sensorimotor regions subserving visual, somatosensory, and motor functions. Using post-mortem transcriptomic data of six donors, we observed that the epicenter map differentiated oligodendrocyte-related transcriptional changes at its sensory apex and the association end was related to expression of excitatory/inhibitory neurons. More generally, we observed that the epicenter map was associated with neurodevelopmental disease gene dysregulation and human accelerated region genes, suggesting potential shared genetic determinants across various neurodevelopmental disorders. Taken together, our results underscore the developmentally rooted pathologic origins of schizophrenia and their transcriptomic overlap with other neurodevelopmental diseases.

neuroscience↗

Presence of NCOR1+/CD4+ T cells in tertiary lymphoid organ predicts favorable prognosis in pancreatic ductal adenocarcinoma

CD4+ T cells have critical roles in anti-tumour immunity and its differentiation is known to be regulated by the nuclear receptor co-repressor 1 (NCOR1). Previous studies suggested that high CD4+ T cells are associated with a favourable prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of NCOR1 in PDAC is still missing. In this study, the pathological impact of NCOR1 and CD4 has been analysed by multiplex immunohistochemistry in 100 PADC patients. NCOR1 expression in tertiary lymphoid organs is positively associated with the good prognosis of PDAC patients, while its expression in tumour tissue is not. Furthermore, the presence of NCOR1+/CD4+ T cells in tertiary lymphoid organs predicts a favourable prognosis in PDAC. Mechanistically, upregulation of NCOR1 expression in CD4+ T cells increases the release of TNF-, which induces the apoptosis of the tumor cells in vitro. Together, our data highlighted the tumour suppressive role of NCOR1+/CD4+ T cells in PDAC.

cancer biology↗

Leafhopper transmits soybean stay-green associated virus to legume plants

A novel geminivirus, soybean stay-green associated virus (SoSGV), was previously shown to cause soybean delayed senescence and is associated with the incidences of soybean stay-green syndrome. The transmission methods of SoSGV were not yet understood. We captured insects belonging to 24 distinct species in a soybean field with the SoSGV outbreak and detected the presence of SoSGV only in leafhoppers and bean bugs (Riptortus pedestris). Caged feeding experiments using captured leafhoppers and bean bugs from soybean fields showed that leafhoppers, but not bean bugs, are vectors transmitting SoSGV. The common brown leafhopper (Orosius orientalis) is identified as the dominant leafhopper species and can establish colonies feeding on soybean plants in experimental conditions. An investigation of SoSGV defective DNA revealed that soybean genomic DNA could be inserted into the SoSGV genome, while sequences from wild soybean, red bean, and cowpea were also identified. We further showed that the common brown leafhopper could transmit SoSGV to wild soybean and red bean plants, emphasizing the vector role of the leafhopper in the transmission of SoSGV in the field.

microbiology↗

Dendritic membrane resistance modulates activity-induced Ca2+ influx in oxytocinergic magnocellular neurons of mouse PVN

Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates there is a flexible relationship between somatic activity and dendritic release, but the mechanisms governing this relationship are not completely understood. Here we use a combination of electrical and optical recording techniques to quantify activity-dependent calcium influx in proximal vs. distal dendrites of oxytocinergic magnocellular neurons located in the paraventricular nucleus of the hypothalamus (OT-MCNs). Results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes, and yet activity-induced dendritic calcium influx can be robustly regulated by a diverse set of stimuli that open or close ionophores located along the dendritic membrane. Overall, this study reveals that dendritic membrane resistance is a dynamic and endogenously regulated feature of OT-MCNs that is likely to have substantial functional impact on central oxytocin release. IMPACT STATEMENTActivity-induced dendritic calcium influx in oxytocinergic magnocellular neurons can be robustly modulated by a highly diverse set of stimuli acting on distinct types of ionophores expressed along the dendritic membrane.

neuroscience↗

ORACA: an open source software for Online Realtime neural Activity extraction and offline Cross session Analysis

The development of in vivo imaging and optogenetic tools makes it possible to control neural circuit activities in an all-optical, closed-loop manner [1], but such applications are limited by the lack of software for online analysis of neuronal imaging data. We developed an analysis software ORCA (Online Real-time activity and offline Cross-session Analysis), which performs image registration, neuron segmentation, and activity extraction at over 100 frames per second, fast enough to support real-time detection and readout of neural activity. Our active neuron detection algorithm is purely statistical, achieving much higher speed than previous methods. We demonstrated closed-loop control of neurons that were identified on the fly, without prior recording or image processing. ORCA also includes a cross-session alignment module that efficiently tracks neurons across multiple sessions. In summary, ORCA is a powerful toolbox for fast imaging data analysis, and provides a solution for all-optical closed-loop control of neuronal activity.

neuroscience↗

A Bayesian method for rare variant analysis using functional annotations and its application to Autism

Rare variant analysis is commonly used in whole-exome or genome sequencing studies. Compared to common variants, rare variants tend to have larger effect sizes and often directly point out causal genes. These potential benefits make association analysis with rare variants a priority for human genetics researchers. To improve the power of such studies, numerous methods have been developed to aggregate information of all variants of a gene. However, these gene-based methods often make unrealistic assumptions, e.g. the commonly used burden test effectively assumes that all variants chosen in the analysis have the same effects. In practice, current methods are often underpowered. We propose a Bayesian method: MIxture model based Rare variant Analysis on GEnes (MIRAGE). MIRAGE analyzes summary statistics, i.e. variant counts from inherited variants in trio-sequencing or from ancestry-matched case-control studies. MIRAGE captures the heterogeneity of variant effects by treating all variants of a gene as a mixture of risk and non-risk variants, and uses external information of variants to model the prior probabilities of being risk variants. We demonstrate in both simulations and analysis of an exome-sequencing dataset of autism, that MIRAGE significantly outperforms current methods for rare variant analysis. The top genes identified by MIRAGE are highly enriched with known or plausible autism risk genes. MIRAGE is available at https://xinhe-lab.github.io/mirage.

genetics↗

Dopaminergic neurons mediate male Drosophila courtship motivational state

Motivational states are important determinants of behavior. In Drosophila melanogaster, courtship behavior is robust and crucial for species continuation. However, the motivation of courtship behavior remains unexplored. We first find the phenomenon that courtship behavior is modulated by motivational state. A male fly courts another male fly when it first courts a decapitated female fly however, male- male courtship behavior rarely occurs under normal conditions. Male flies that have satisfied the need for sexual behavior show a decreased male-female sex drive. Therefore, in this phenomenon, the male flys courtship motivational state is induced by its exposure to female flies. Blocking dopaminergic neurons by expressing TNTe decreases motivational state-induced male-male courtship behavior without affecting male-female courtship behavior. Vision cues are another key component in sexually driven male-female courtship behavior. Here, we identify a base theory that the inner motivational state could eventually decide fly behavior.

neuroscience↗

PCIF1 catalyzes m6Am mRNA methylation to regulate gene expression

mRNA modifications play an important role in regulating gene expression. One of the most abundant mRNA modifications is N6,2-O-dimethyladenosine (m6Am). Here, we demonstrate that m6Am is an evolutionarily conserved mRNA modification mediated by the Phosphorylated CTD Interacting Factor 1 (PCIF1), which catalyzes m6A methylation on 2-O-methylated adenine located at the 5 ends of mRNAs. Furthermore, PCIF1 catalyzes only 5 m6Am methylation of capped mRNAs, but not internal m6A methylation in vitro and in vivo. Our global mRNA methylation analysis revealed that there is no crosstalk between m6Am and m6A mRNA methylation events, suggesting that m6Am is functionally distinct from m6A. Importantly, our data indicate that m6Am negatively impacts translation of methylated mRNAs by antagonizing cap binding protein eIF4E. Together, we identify the first and only human mRNA m6Am methyltransferase and demonstrate a novel mechanism of gene expression regulation through PCIF1-mediated m6Am mRNA methylation in eukaryotes.\n\nHighlightsO_LIPCIF1 is an evolutionarily conserved mRNA m6Am methyltransferase\nC_LIO_LILoss of PCIF1 leads to a complete loss of m6Am, whereas m6A level and distribution are not affected\nC_LIO_LIPCIF1 mediated m6Am does not affect RNA Pol II transcription or mRNA stability\nC_LIO_LIm6Am-Exo-Seq is a robust methodology that enables global m6Am mapping\nC_LIO_LIm6Am suppresses cap dependent translation\nC_LI

molecular biology↗