Biology subjects

Jiang, X.

Publications and source records attributed to Jiang, X..

At least 289 records · Page 16Linked to original sources

bioRxiv2022

Genome-wide identification of SINA gene family in sugarcane and functional analysis of SsSINA1a in drought response

Sugarcane (Saccharum spp. hybrid) is a crucial sugar and energy crop that provides majority of the raw material for sugar and ethanol production globally. Drought represents one of the most critical constraints of sugarcane production in the subtropical parts of China. SEVEN IN ABSENTIA (SINA) act as an important E3 ubiquitin ligase and play a significant role in plant stress responses. However, the characteristics of the sugarcane SINA gene family have not been previously studied currently. Here, we identified 15 SsSINA in Saccharum spontaneum, 5 ShSINA in Saccharum spp. hybrid and 6 SbSINA in Sorghum bicolor based on their conserved N{square}terminal RING and C-terminal SINA domains, and these genes were distributed into three phylogenetic groups (I, {square} and {square}). Collinearity analysis showed a close genetic relationship between the SINA genes of S. spontaneum and S. bicolor. The cis-regulatory elements in the promoter regions of the SINA genes were involved in a variety of plant physiological responses. Further, we identified a SINA gene SsSINA1a that significantly induced by drought stress. Overexpression of SsSINA1a enhanced drought tolerance in Arabidopsis through reducing leaf water loss rate. These finding indicate that SsSINA1a mediates plant drought tolerance and this study provides a new potential candidate gene for sugarcane drought-resistant breeding.

molecular biology↗

bioRxiv2022

Nrf2 prevents diabetic cardiomyopathy via antioxidation and normalization of glucose and lipid metabolism in the heart

ObjectiveMetabolic disorders and oxidative stress are the main causes of diabetic cardiomyopathy. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts a powerful antioxidant effect and prevents the progression of diabetic cardiomyopathy. However, the mechanism of its cardiac protection and direct action on cardiomyocytes are not well understood. MethodsIn this study, cardiomyocyte-restricted Nrf2 transgenic mice (Nrf2-TG) were used to directly observe whether cardiomyocyte-specific overexpression of Nrf2 can prevent diabetic cardiomyopathy and correct glucose and lipid metabolism disorders in the heart. ResultsCompared to wild-type (WT) mice, Nrf2-TG mice showed resistance to diabetic cardiomyopathy in a streptozotocin (STZ)-induced type 1 diabetes mouse model. This was primarily manifested as improved echocardiography results as well as reduced myocardial fibrosis, cardiac inflammation, and oxidative stress. ConclusionThese results showed that Nrf2 can directly act on cardiomyocytes to play a cardioprotective role. Mechanistically, the cardioprotective effects of Nrf2 depend on its antioxidation activity, partially through improving glucose and lipid metabolism by targeting the metabolic pathways of Akt/GSK-3 {beta}/HK-II and AMPK/Sirt1/PGC-1.

molecular biology↗

bioRxiv2022

An immune-lncRNA risk model to predict prognosis for patients with head and neck squamous cell carcinoma

Backgroundlong noncoding RNA (lncRNA) are closely correlated with the occurrence and development of tumors. The purpose of this research is to construct a risk model of immune-related lncRNAs that can be used for predicting the survival and prognosis of head and neck squamous cell carcinoma (HNSCC) patients and further exploring the immune function of immune-lncRNAs. Methodsobtained detailed transcriptional data and clinical information for 545 cases of HNSCC from The Cancer Genome Atlas (TCGA). Combined lncRNAs and the immune gene sets from the Molecular Signatures Database (MSigDB) were employed to construct co{square}expression networks, the significant correlation of immune-lncRNAs obtained from the results of Cox regression analysis were used to build the model. Survival analysis and QRT-PCR were used to confirm the expression of immune-lncRNAs and optimize the risk model. Then single-cell RNA Sequencing (scRNA-seq) dataset analysis of laryngeal squamous cell carcinoma (LSCC), co-expression analysis, correlation analysis and immunohistochemistry were used to explore the immune function of immune-lncRNAs. ResultsA total of 13 immune-lncRNAs including AC104083.1AC004148.2AL357033.4AC116914.2AC024075.1AC008115.3PCED1B-AS1RAB11B-AS1AC004687.1 AL450992.2EP300-AS1AC024075.2AC136475.2 were identified to construct the risk model. In this model, low-risk patients had higher overall survival (OS, P=1.923e-12, hazard ratio=2.104, 95% CI: 1.622-2.730). AC004687.1 and PCED1B-AS1 were overexpressed in T cells and were closely related to the genes encoding major histocompatibility complex II (MHC II) molecules. And the results of QRT-PCR and immunohistochemistry showed the expression significant positively correlated with HLA-DR which is one of the MHC II classical molecules. Conclusionthe immune-associated risk model constructed by 13 lncRNAs has good prognostic value for HNSCC. AC004687.1 and PCED1B-AS1 are significant correlating to clinical characteristics and MHC II, we provide a new insight into the immune function of lncRNAs.

bioinformatics↗

bioRxiv2022

Cellular and Circuit Organization of the Locus Coeruleus of Adult Mice

The locus coeruleus (LC) houses the vast majority of noradrenergic neurons in the brain and regulates many fundamental functions including fight and flight response, attention control, and sleep/wake cycles. While efferent projections of the LC have been extensively investigated, little is known about its local circuit organization. Here, we performed large-scale multi-patch recordings of noradrenergic neurons in adult mouse LC to profile their morpho-electric properties while simultaneously examining their interactions. LC noradrenergic neurons are diverse and could be classified into two major morpho-electric types. While fast excitatory synaptic transmission among LC noradrenergic neurons was not observed in our preparation, these mature LC neurons connected via gap junction at a rate similar to their early developmental stage and comparable to other brain regions. Most electrical connections form between dendrites and are restricted to narrowly spaced pairs or small clusters of neurons of the same type. In addition, more than two electrically coupled cell pairs were often identified across a cohort of neurons from individual multi-cell recording sets that followed a chain-like organizational pattern. The assembly of LC noradrenergic neurons thus follows a spatial and cell type-specific wiring principle that may be imposed by a unique chain-like rule.

neuroscience↗

bioRxiv2022

The structure of insulin granule core determines secretory capacity being reduced in type-2 diabetes

Exocytosis in excitable cells is essential for their physiological functions. Although the exocytotic machinery controlling cellular secretion has been well investigated, the function of the vesicular cargo, i.e. secretory granular content remains obscure. Here we combine dSTORM imaging and single-domain insulin antibody, to dissect the in situ structure of insulin granule cores (IGCs) at nano level. We demonstrate that the size and shape of the IGCs can be regulated by the juxta-granular molecules Nucleobindin-2 and Enolase-1, that further contribute to the stimulated insulin secretion. IGCs located at the plasma membrane are larger than those in the cytosol. The IGCs size is decreased by [~]20% after glucose stimulation due to the release of the peripheral part of IGCs through incomplete granule fusion. Importantly, the reduction of the IGCs size is also observed in non-stimulatory pancreatic {beta}-cells from diabetic db/db mice, Akita (Ins2+/-) mice and human Type-2 diabetic donors, in accordance with impaired secretion. These findings overall highlight the structure of exocytotic insulin cores as a novel modality amenable to targeting in the stimulated exocytosis in {beta}-cells with impaired insulin secretion.

physiology↗

bioRxiv2022

A Self-attention Graph Convolutional Network for Precision Multi-tumour Early Diagnostics with DNA Methylation Data

DNA methylation data-based precision tumor early diagnostics is emerging as state of the art technology, which could capture the signals of cancer occurrence 3[~]5 years in advance and clinically more homogenous groups. At present, the sensitivity of early detection for many tumors is about 30%, which needs to be significantly improved. Nevertheless, based on the genome wide DNA methylation information, one could comprehensively characterize the entire molecular genetic landscape of the tumors and subtle differences among various tumors. With the accumulation of DNA methylation data, we need to develop high-performance methods that can model and consider more unbiased information. According to the above analysis, we have designed a self-attention graph convolutional network to automatically learn key methylation sites in a data-driven way for precision multi-tumor early diagnostics. Based on the selected methylation sites, we further trained a multi-class classification support vector machine. Large amount experiments have been conducted to investigate the performance of the computational pipeline. Experimental results demonstrated the effectiveness of the selected key methylation sites which are highly relevant for blood diagnosis.

bioinformatics↗

bioRxiv2022

Single-cell multi-region dissection of brain vasculature in Alzheimer's Disease

Cerebrovascular breakdown occurs early in Alzheimers Disease (AD), but its cell-type-specific molecular basis remains uncharacterized. Here, we characterize single-cell transcriptomic differences in human cerebrovasculature across 220 AD and 208 control individuals and across 6 brain regions. We annotate 22,514 cerebrovascular cells in 11 subtypes of endothelial, pericyte, smooth muscle, perivascular fibroblast, and ependymal cells, and how they differ in abundance and gene expression between brain regions. We identify 2,676 AD-differential genes, including lower expression of PDGFRB in pericytes, and ABCB1 and ATP10A in endothelial cells. These AD-differential genes reveal common upstream regulators, including MECOM, EP300, and KLF4, whose targeting may help restore vasculature function. We find coordinated vasculature-glial-neuronal co-expressed gene modules supported by ligand-receptor pairs, involved in axon growth/degeneration and neurogenesis, suggesting mechanistic mediators of neurovascular unit dysregulation in AD. Integration with AD genetics reveals 125 AD-differential genes directly linked to AD-associated genetic variants (through vasculature-specific eQTLs, Hi-C, and correlation-based evidence), 559 targeted by AD-associated regulators, and 661 targeted by AD-associated ligand-receptor signaling. Lastly, we show that APOE4-genotype associated differences are significantly enriched among AD-associated genes in capillary and venule endothelial cells, and subsets of pericytes and fibroblasts, which underlie the vascular dysregulation in APOE4-associated cognitive decline. Overall, our multi-region molecular atlas of differential human cerebrovasculature genes and pathways in AD can help guide early-stage AD therapeutics.

neuroscience↗

bioRxiv2022

Comprehensive preclinical evaluation of human-derived anti-poly-GA antibodies in cellular and animal models of C9ORF72 disease

Hexanucleotide G4C2 repeat expansions in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) generated by translation of repeat-containing RNAs show toxic effects in vivo as well as in vitro and are key targets for therapeutic intervention. We generated human antibodies that bind DPRs with high affinity and specificity. Anti-GA antibodies engaged extra- and intracellular poly-GA and reduced aggregate formation in a poly-GA over-expressing human cell line. However, antibody treatment in human neuronal cultures synthesizing exogenous poly-GA resulted in the formation of large extracellular immune complexes and did not affect accumulation of intracellular poly-GA aggregates. Treatment with antibodies was also shown to directly alter the morphological and biochemical properties of poly-GA and to shift poly-GA/antibody complexes to more rapidly sedimenting ones. These alterations were not observed with poly-GP and have important implications for accurate measurement of poly-GA levels including the need to evaluate all centrifugation fractions and disrupt the interaction between treatment antibodies and poly-GA by denaturation. Targeting poly-GA and poly-GP in two mouse models expressing G4C2 repeats by systemic antibody delivery for up to 16 months was well-tolerated and led to measurable brain penetration of antibodies. Long term treatment with anti-GA antibodies produced improvement in an open field movement test in aged C9ORF72450 mice. However, chronic administration of anti-GA antibodies in AAV-(G4C2)149 mice was associated with increased levels of poly-GA detected by immunoassay and did not significantly reduce poly-GA aggregates or alleviate disease progression in this model. SignificanceImmunotherapy has been proposed for neurodegenerative disorders including Alzheimers or Parkinsons diseases. Recent reports using antibodies against poly-GA or active immunization suggested similar immunotherapy in ALS/FTD caused by repeat expansion in the C9ORF72 gene (1, 2). Here, we systematically characterized human antibodies against multiple DPR species and tested the biological effects of antibodies targeting poly-GA in different cellular and mouse models. Target engagement was shown in three independent cellular models. Anti-GA antibodies reduced the number of intracellular poly-GA aggregates in human T98G cells but not in cultured human neurons. Whereas chronic anti-GA treatment in BAC C9ORF72450 mice did not impact poly-GA levels and modestly improved one behavioral phenotype, poly-GA levels detected by immunoassays were increased and disease progression was unaltered in AAV-(G4C2)149 mice.

neuroscience↗

bioRxiv2022

Putative host-derived insertions in the genome of circulating SARS-CoV-2 variants

Insertions in the SARS-CoV-2 genome have the potential to drive viral evolution, but the source of the insertions is often unknown. Recent proposals have suggested that human RNAs could be a source of some insertions, but the small size of many insertions makes this difficult to confirm. Through an analysis of available direct RNA sequencing data from SARS-CoV-2 infected cells, we show that viral-host chimeric RNAs are formed through what are likely stochastic RNA-dependent RNA polymerase template switching events. Through an analysis of the publicly available GISAID SARS-CoV-2 genome collection, we identified two genomic insertions in circulating SARS-CoV-2 variants that are identical to regions of the human 18S and 28S rRNAs. These results provide direct evidence of the formation of viral-host chimeric sequences and the integration of host genetic material into the SARS-CoV-2 genome, highlighting the potential importance of host-derived insertions in viral evolution. IMPORTANCEThroughout the COVID-19 pandemic, the sequencing of SARS-CoV-2 genomes has revealed the presence of insertions in multiple globally circulating lineages of SARS-CoV-2, including the Omicron variant. The human genome has been suggested to be the source of some of the larger insertions, but evidence for this kind of event occurring is still lacking. Here, we leverage direct RNA sequencing data and SARS-CoV-2 genomes to show host-viral chimeric RNAs are generated in infected cells and two large genomic insertions have likely been formed through the incorporation of host rRNA fragments into the SARS-CoV-2 genome. These host-derived insertions may increase the genetic diversity of SARS-CoV-2 and expand its strategies to acquire genetic materials, potentially enhancing its adaptability, virulence, and spread.

bioinformatics↗

bioRxiv2021

Structure and dynamics of human disease-complication network

A complication is an unanticipated disease arisen following, induced by a disease, a treatment or a procedure. We compile the Human Disease-Complication Network from the medical data and investigate the characteristics of the network. It is observed that the modules of the network are dominated by the classes of diseases. The relations between modules are unveiled in detail. Three nontrivial motifs are identified from the network. We further simulate the dynamics of motifs with the Boolean dynamic model. Each motif represents a specific dynamic behavior, which is potentially functional in the disease system, such as generating temporal progressions and governing the responses to fluctuating external stimuli. Author summaryAdvances in molecular biology lead to a new discipline of network medicine, investigating human diseases in a networked structure perspective. Recently, clinical records have been introduced to the research of complex networks of diseases. An important available medical dataset that has been overlooked so far is the complications of diseases, which are vital for human beings. We compile the Human Disease-Complication Network, representing the causality between the upstream diseases and their downstream complications. This work not only helps us to comprehend why certain groups of diseases appear collectively, but also provides a new paradigm to investigate the dynamics of disease progression. For clinical applications, the investigation of complications may yield new approaches to disease prevention, diagnosis and treatment.

bioinformatics↗

bioRxiv2021

Azotobacter vinelandii scaffold protein NifU transfers iron to NifQ as part of the iron-molybdenum cofactor biosynthesis pathway for nitrogenase

Azotobacter vinelandii molybdenum-dependent nitrogenase obtains molybdenum from NifQ, a monomeric iron-sulfur molybdoprotein. This protein requires of a preexisting [Fe-S] cluster to form a [MoFe3S4] group to serve as specific donor during nitrogenase cofactor biosynthesis. Here, we show biochemical evidence for NifU being the donor of the [Fe-S] cluster. Protein-protein interaction studies using apo-NifQ and as-isolated NifU demonstrated the interaction between both proteins which is only effective when NifQ is unoccupied by its [Fe-S] cluster. The apo-NifQ iron content increased after the incubation with as-isolated NifU, reaching similar levels to holo-NifQ after the interaction between apo-NifQ and NifU with reconstituted transient [Fe4-S4] groups. These results also indicate the necessity of co-expressing NifU together with NifQ in the pathway to provide molybdenum for the biosynthesis of nitrogenase in engineered nitrogen-fixing plants.

biochemistry↗

bioRxiv2021

Fine-grained, nonlinear image registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes

We present an application of non-linear Image registration that allows spatiotemporal analysis of extremely noisy and diffuse molecular processes across the entire cell. To produce meaningful local tracking of the spatially coherent portion of diffuse protein dynamics, we improved upon existing non-linear image registration to compensate for cell movement and deformation. The registration relies on a subcellular fiducial marker, a cell motion mask, and a topological regularization that enforces diffeomorphism on the registration without significant loss of granularity. We demonstrate the potential of this approach in conjunction with stochastic time-series analysis through the discovery of distinct zones of coherent Profillin dynamics in symmetry-breaking U2OS cells. Further analysis of the resulting Profilin dynamics revealed strong relationships with the underlying actin organization. This study thus provides a framework for extracting functional interactions between cell morphodynamics, protein distributions, and signaling in cells undergoing continuous shape changes. Author SummaryBy adapting optical flow based nonlinear image registration we created a method specific for live cell movies that preserves the dynamics of a signal of interest by remapping using a separate measurable subcellular location fiducial. This is an extension as well on our labs previously published method of cell edge-based referencing of subcellular locations that was incapable of extracting interpretable subcellular time series more than a few microns away from the cell edge. We showed that our method overcomes this key limitation and allows sampling of subcellular time series from every subcellular location through our discovery of organized profilin dynamics in moving cell and that these profilin dynamics are related to actin dynamics due to their ability to bind growing actin structures likely through actin polymerizing factors. Most importantly, our method is applicable to discovering subcellular organization and coordination in a widely used form of live cell microscopy data that hitherto has been largely limited to anecdotal analysis.

bioinformatics↗

bioRxiv2021

Computational Compensatory Mutation Discovery Approach: Predicting a PARP1 Variant Rescue Mutation

The prediction of protein mutations that affect function may be exploited for multiple uses. In the context of disease variants, the prediction of compensatory mutations that reestablish functional phenotypes could aid in the development of genetic therapies. In this work, we present an integrated approach that combines coevolutionary analysis and molecular dynamics (MD) simulations to discover functional compensatory mutations. This approach is employed to investigate possible rescue mutations of a poly(ADP-ribose) polymerase 1 (PARP1) variant, PARP1 V762A, associated with lung cancer and follicular lymphoma. MD simulations show PARP1 V762A exhibits noticeable changes in structural and dynamical behavior compared with wild type PARP1. Our integrated approach predicts A755E as a possible compensatory mutation based on coevolutionary information, and molecular simulations indicate that the PARP1 A755E/V762A double mutant exhibits similar structural and dynamical behavior to WT PARP1. Our methodology can be broadly applied to a large number of systems where single nucleotide polymorphisms (SNPs) have been identified as connected to disease and can shed light on the biophysical effects of such changes as well as provide a way to discover potential mutants that could restore wild type-like functionality. This can in turn be further utilized in the design of molecular therapeutics that aim to mimic such compensatory effect. Significance StatementDiscovering protein mutations with desired phenotypes can be challenging due to its combinatorial nature. Herein we employ a methodology combining gene SNP association to disease, direct coupling analysis and molecular dynamics simulations to systematically predict rescue mutations. Our workflow identifies A755E as a potential rescue for the PARP1 V762A mutation, which has been associated with cancer. This methodology is general and can be applied broadly.

biophysics↗

bioRxiv2021

SARS-CoV-2 RdRp is a versatile enzyme with proofreading activity and ability to incorporate NHC into RNA by using diphosphate form molnupiravir as a substrate

The coronavirus disease 2019 (COVID-19) has been ravaging throughout the world for more than two years and has severely impaired both human health and the economy. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs the viral RNA-dependent RNA polymerase (RdRp) complex for genome replication and transcription, making RdRp an appealing target for antiviral drug development. Here, we reveal that RdRp can recognize and utilize nucleoside diphosphates (NDPs) as a substrate to synthesize RNAs with an efficiency of about two thirds of using nucleoside triphosphates (NTPs) as a substrate. NDPs incorporation is also template-specific and has high fidelity. Moreover, RdRp can incorporate {beta}-d-N4-hydroxycytidine (NHC) into RNA while using diphosphate form molnupiravir (MDP) as a substrate. We also observed that MDP is a better substrate for RdRp than the triphosphate form molnupiravir (MTP).

molecular biology↗

bioRxiv2021

Imaging the Extent and Location of Spatiotemporally Distributed Epileptiform Sources from MEG Measurements

Non-invasive MEG/EEG source imaging provides valuable information about the epileptogenic brain areas which can be used to aid presurgical planning in focal epilepsy patients suffering from drug-resistant seizures. However, the source extent estimation for electrophysiological source imaging remains to be a challenge and is usually largely dependent on subjective choice. Our recently developed algorithm, fast spatiotemporal iteratively reweighted edge sparsity minimization (FAST-IRES) strategy, has been shown to objectively estimate extended sources from EEG recording, while it has not been applied to MEG recordings. In this work, through extensive numerical experiments and real data analysis in a group of focal drug-resistant epilepsy patients interictal spikes, we demonstrated the ability of FAST-IRES algorithm to image the location and extent of underlying epilepsy sources from MEG measurements. Our results indicate the merits of FAST-IRES in imaging the location and extent of epilepsy sources for pre-surgical evaluation from MEG measurements.

bioengineering↗

bioRxiv2021

Transcriptome analysis of SARS-CoV-2 naive and recovered individuals vaccinated with inactivated vaccine

The urgent approval of the use of the inactivated COVID-19 vaccine is essential to reduce the threat and burden of the epidemic on global public health, however, our current understanding of the host immune response to inactivated vaccine remains limited. Herein, we performed serum IgG antibody detection and transcriptomics analysis on 20 SARS-CoV-2 naive individuals who received multiple doses of inactivated vaccine and 5 SARS-CoV-2 recovered individuals who received single dose of inactivated vaccine. Our research revealed the important role of many innate immune pathways after vaccination, identified a significant correlation with the third dose of booster vaccine and proteasome-related genes, and found that SARS-CoV-2 recovered individuals can produces a strong immune response to a single dose of inactivated vaccine. These results help us understand the reaction mechanism of the hosts molecular immune system to the inactivated vaccine, and provide a basis for the choice of vaccination strategy.

microbiology↗

bioRxiv2021

Calcium-independent but voltage-dependent secretion (CiVDS) mediates synaptic transmission in a mammalian central synapse

A central principle of synaptic transmission is that action potential-induced presynaptic neurotransmitter release occurs exclusively via Ca2+-dependent secretion (CDS). The discovery and mechanistic investigations of Ca2+-independent but voltage-dependent secretion (CiVDS) have demonstrated that the action potential per se is sufficient to trigger neurotransmission in the somata of primary sensory and sympathetic neurons in mammals. One key question remains, however, whether CiVDS contributes to central synaptic transmission. Here we report, in the central transmission from presynaptic (dorsal root ganglion) to postsynaptic (spinal dorsal horn) neurons, (1) excitatory postsynaptic currents (EPSCs) are mediated by glutamate transmission through both CiVDS (up to 87%) and CDS; (2) CiVDS-EPSCs are independent of extracellular and intracellular Ca2+; (3) CiVDS is >100 times faster than CDS in vesicle recycling with much less short-term depression; (4) the fusion machinery of CiVDS includes Cav2.2 (voltage sensor) and SNARE (fusion pore). Together, an essential component of activity-induced EPSCs is mediated by CiVDS in a central synapse.

neuroscience↗

bioRxiv2021

Dalpiciclib and Pyrotinib Exert Synergistic Antitumor Effects in Triple Positive Breast Cancer

BackgroundThe therapeutic benefit of the standard combination of anti-HER2 and chemotherapy in triple-positive breast cancer (TPBC) is limited even after the addition of endocrine therapy to the regimen. Therefore, treatment optimization is required urgently. MethodsThrough the drug sensitivity test, the drug combination efficacy of anti-HER2 drug, endocrine drug and CDK4/6 inhibitor to BT474 cells were tested. The underlying molecular mechanisms were investigated using immunofluorescence, western blot analysis, immunohistochemical staining and cell cycle analysis. Potential biomarker which may indicate the responsiveness to drug treatment in triple positive breast cancer was selected out using RNA-sequence and tested using immunohistochemical staining. ResultsWe found that pyrotinib combined with dalpiciclib showed better efficacy than pyrotinib combined with tamoxifen in BT474 cells. Degradation of HER2 could enhance ER nuclear transportation, whereas cell cycle blockers could reverse this process. This may be the underlying mechanism by which the addition of dalpiciclib was more beneficial than the addition of pyrotinib plus tamoxifen. Furthermore, CALML5 was revealed to be a potential indicator of responsiveness to anti-HER2 therapy plus CDK4/6 inhibition in triple positive breast cancer. ConclusionOur study provided evidence for the introduction of CDK4/6 inhibitor in the treatment of TPBC and indicated that the combination of anti-HER2 therapy and cell cycle blockers may be a better strategy for TPBC treatment. FundingThis study was supported by the National Natural Science Foundation of China (#U20A20381, #81872159)

cell biology↗