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Biology subjects

Yu, X.

Publications and source records attributed to Yu, X..

At least 361 records · Page 20Linked to original sources

Lactate Increases Stemness of CD8+ T Cells to Augment Anti-Tumor Immunity

Nutrients and metabolites play important roles in immune functions. Recent studies show lactate instead of glucose can serve as a primary carbon fuel source for most tissues. The role of lactate in tumor immunity is not well understood with immune suppressive functions reported for lactic acid, the conjugate acid form of lactate. In this study, we report lactate increases the stemness of CD8+ T cells and augments anti-tumor immunity. Subcutaneous administration of lactate but not glucose shows CD8+ T cell-dependent tumor growth inhibition. Single cell transcriptomics analysis revealed lactate treatment increased a subpopulation of stem-like TCF-1-expressing CD8+ T cells, which is further validated by ex vivo culture of CD8+ T cells from mouse splenocytes and human peripheral blood mononuclear cells. The inhibition of histone deacetylase activity by lactate increased acetylation in the histone H3K27 site at the Tcf7 super enhancer locus and increased the gene expression of Tcf7. Adoptive transfer of CD8+ T cells pretreated with lactate in vitro showed potent tumor growth inhibition in vivo. Our results elucidate the immune protective role of lactate in anti-tumor immunity without the masking effect of acid. These results may have broad implications for T cell therapy and the understanding of lactate in immune metabolism.

immunology↗

Cryo-electron microscopy revealed TACAN is extensively and specifically associated with membrane lipids

TACAN is not a mechanosensitive ion channel but significantly linked to the mechanical hyperalgesia. In this study, we show that the human TACAN is a homodimer with each monomer consisting of a body, a spring and a blade domains. The body domain contains six transmembrane helices that forms an independent channel. The spring domain adapts a loop-helix-loop configuration with the helix running within and parallel to the membrane. The blade domain is composed of two cytoplasmic helices. In addition, we found that all the helices of the body and the spring domains are specifically associated with membrane lipids. Particularly, a lipid core, residing within a cavity formed by the two body and spring domains, contacts with the helices from the body and spring domains and extends to reach two symmetrically arranged lipid clusters. These results extremely imply that the membrane lipids coordinate with the membrane-embedded protein to sense and transduce the mechanic signal.

biophysics↗

Characterizing brain state-dependent pupil dynamics based on lateral hypothalamic activity

Pupil dynamics presents varied correlation features with brain activity under different vigilant levels. The modulation of brain state changes can arise from the lateral hypothalamus (LH), where diverse neuronal cell types contribute to arousal regulation in opposite directions via the anterior cingulate cortex (ACC). However, the relationship of the LH and pupil dynamics has seldom been investigated. Here, we performed local field potential (LFP) recordings at the LH and ACC, and the whole brain fMRI with simultaneous fiber photometry Ca2+ recording in the ACC, to evaluate their correlation with brain state-dependent pupil dynamics. Both LFP and functional MRI (fMRI) data showed opposite correlation features to pupil dynamics, demonstrating an LH activity-dependent manner. Our results demonstrate that the correlation of pupil dynamics with ACC LFP and whole-brain fMRI signals depends on LH activity, indicating a role of the latter in brain state regulation.

neuroscience↗

Discovery of cell active macrocyclic peptides with on-target inhibition of KRAS signaling

RAS is the most commonly mutated oncogene in human cancers and RAS-driven tumors are amongst the most difficult to treat. Historically, discovery of therapeutics targeting this protein has proven challenging due to a lack of deep hydrophobic pockets to which a small molecule might bind. The single such pocket available is normally occupied by GDP or GTP which have millimolar cellular concentrations and picomolar affinities for KRAS and hence is challenging to target. The recent FDA approval of sotorasib, a covalent modifier of the KRASG12C mutant protein, has clinically validated KRAS as an oncology target. However, traditional challenges remain for targeting the more common KRAS mutations such as G12D and G12V. As an alternative approach, we investigated the superior binding capacity of macrocyclic peptides to identify KRAS inhibitory molecules. We focused on the recently reported disulfide-cyclized arginine-rich peptide KRpep-2d, discovered through phage display and previously independently confirmed by us as a bona fide KRAS binder. To mitigate intracellular disulfide reduction and loss of binding, we identified an alternate cyclization motif by inverting the configuration of Cys5 and linking it to Cys15 through a thioacetal bridge. The corresponding peptide bound KRAS through cis isomerization of the peptide bond between D-Cys5 and Pro6 as observed through x-ray crystallography. Prototypic molecules displayed measurable cellular inhibition of RAS signaling without membrane lysis and counter-screen off-target activity. An analogue containing azido-lysine confirmed the cell penetrant nature of this molecule using our recently reported NanoClick assay. To improve cellular activity, we sought to improve proteolytic stability. Structure-activity relationship studies identified key scaffold residues critical for binding and revealed that replacement of N- and C-terminal arginine residues with D-arginines and introduction of an -methyl moiety at Ser10 resulted in a molecule with improved proteolytic stability as indicated by its persistence in whole cell homogenate. The resulting peptide MP-3995 had improved and sustained cell-based efficacy. On-target activity was validated through confirmation of target engagement, lack of signaling in irrelevant pathways, and use of non-binding control peptides. Mechanism of action studies suggested that peptide binding to both GDP- and GTP-states of KRAS may contribute to cellular activity. Although validated as bona fide and on-target inhibitors of cell based KRAS signaling, this series is unlikely to advance to the clinic in its current form due to its arginine-dependent cell entry mechanism. Indeed, we showed a strong correlation between net positive charge and histamine release in an ex vivo assay making this series challenging to study in vivo. Nonetheless, these molecules provide valuable templates for further medicinal chemistry efforts aimed at leveraging this unique inhibitory binding site on KRAS. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/459913v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@17f4764org.highwire.dtl.DTLVardef@12818daorg.highwire.dtl.DTLVardef@177bdf0org.highwire.dtl.DTLVardef@57046c_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Augmenting Neutralization breadth against Diverse HIV-1 by increasing the Ab-Ag interface on V2

Understanding maturation pathways of broadly neutralizing antibodies (bnAbs) against HIV-1 in non-human primates can be highly informative for HIV-1 vaccine development. We now obtained a lineage of J038 from Chinese rhesus macaques after 7-years of SHIV infection. J038 has short complementary determining loops and neutralizes 54% of global circulating HIV-1 strains. Its binding induces a unique "up" conformation for one of the V2 loops in the trimeric envelope glycoprotein (Env) and is heavily dependent on glycan, which provides nearly half of the binding surface. The unmutated common ancestor of the J038 lineage antibodies binds monomeric gp120 and neutralizes the autologous virus. Continuous maturation enhances neutralization potency and breadth of J038 lineage antibodies via expanding antibody-Env contact areas surrounding the core region contacted by germline-encoded residues. Developmental details and recognition features of J038 lineage antibodies revealed here provide a new pathway for maturation elicitation of V2-targeting bnAbs. Highlights* Long-term infected NHPs develop antibodies neutralizing up to 54% of HIV-1 strains * Antibody J038 binds one V2 loop on HIV-1 Env trimer in a unique "up" position * UCA of the J038 lineage effectively neutralizes the autologous virus * J038 lineage antibodies mature through gradually increased contact to glycans

immunology↗

Distinctive neural correlates of phonological processing and reading impairment in fetal alcohol-exposed adolescents with and without facial dysmorphology

AbstractO_ST_ABSBackgroundC_ST_ABSPrenatal alcohol exposure (PAE) has been linked to atypical brain development and a wide range of cognitive and behavioral impairments, including poor reading performance in childhood and adolescence. However, little is known about how structural and/or functional teratogenesis in the brain mediate reading impairment in fetal alcohol spectrum disorders (FASD) and whether neural correlates of reading and phonological processing differ between FASD subtypes with different clinical presentations in facial morphology. MethodsThe current study utilized functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to characterize functional and structural mechanisms mediating reading deficits in 26 syndromal adolescents with PAE-related facial dysmorphology (i.e., fetal alcohol syndrome (FAS) or partial FAS (PFAS)) and 30 heavily exposed (HE) without this dysmorphology, in comparison with 19 typically developing controls. Importantly, the levels of PAE and reading ability were comparable between the FAS/PFAS and HE groups in the current study. ResultsCompared to the nonsyndromal HE and control groups, the syndromal adolescents showed greater activation in the right precentral gyrus during an fMRI phonological processing task and rightward lateralization in an important reading-related tract (inferior longitudinal fasciculus, ILF), suggesting an atypical reliance on the right hemisphere during reading. By contrast, in the HE group, better reading skills were associated with increased neural activation in the left angular gyrus (LAG) and higher fractional anisotropy in the white matter organization of the left ILF. However, the brain function-behavior relation was weaker in the HE than among the controls, suggesting less efficient function of the typical reading neural network that may contribute to the observed reading impairments. ConclusionsOur findings provide the first evidence for the distinctive functional and structural mechanisms underlying atypical reading and phonological processing in PAE adolescents with and without FAS facial dysmorphology. HighlightsO_LIPrenatal alcohol exposure is associated with altered neural reading networks C_LIO_LIFASD subtypes exhibit distinctive neural correlates of phonological processing C_LIO_LIGreater right-hemispheric reliance was observed in FASD with facial dysmorphology C_LIO_LINon-syndromal FASD showed deficits in the typical left-hemispheric reading network C_LI

neuroscience↗

Identification of Potent Small Molecule Inhibitors of SARS-CoV-2 Entry

The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, Calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals Calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.

microbiology↗

Ifenprodil Intracerebrally Offers Neuroprotection against 6-OHDA-Induced Toxicity in SD-Rats via Enhancing Autophagy Function

The progressive decline of dopamine neurons in the substantia nigra is the main pathogenic change in Parkinsons disease (PD). Studies have found that excessive excitement of glutamatergic neurons causes intracellular calcium overload and induces autophagy impairment, which is one of the main mechanisms of dopamine neuron damage. The neuroprotective effect of Ifenprodil against 6-OHDA-injured mice was studied in this study. Ifenprodil was administered intraperitoneally (i.p.) or intracerebrally to rats who had a nigral-striatum pathway lesioned by 6-OHDA stereotactic brain injection. The ability to move was evaluated. The survival of dopamine neurons in the nigral was determined using HE staining, while TH-positive expression was measured using immunohistochemistry. Western Blot was used to examine the expression of CaM protein and light chain 3 (LC3), Beclin-1, BNIP3LNix, and p62. The results revealed that Ifenprodil improves motor function in 6-OHDA rats, and intracerebral injection is more effective than systemic administration. The same results also found in HE and IHC. Ifenprodil enhanced LC3II, BNIP3LNix, and Beclin-1 while decreasing p62, p-CaMKII, and {beta}-Ca expression. In addition, Ifenprodil reduced the activation of microglia caused by 6-OHDA. Overall, the findings imply that Ifenprodil intracerebrally may protect against Parkinsons disease via modulating autophagy-related proteins during 6-OHDA-induced toxicity.

neuroscience↗

The human neuronal receptor NgR1 bridges reovirus capsid proteins to initiate infection

Human Nogo-66 receptor 1 (NgR1) is a receptor for mammalian orthoreoviruses (reoviruses), but the mechanism of virus-receptor engagement is unknown. NgR1 binds a variety of structurally dissimilar ligands in the adult central nervous system (CNS) to inhibit axon outgrowth. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron regrowth, making NgR1 an important therapeutic target for diverse conditions such as spinal crush injuries and Alzheimer disease. To elucidate how NgR1 mediates cell binding and entry of reovirus, we defined the affinity of interaction between virus and receptor, determined the structure of the virus-receptor complex, and identified residues in the receptor required for virus binding and infection. These studies revealed that NgR1 sequences in a central concave region of the molecule establish a bridge between two copies of the viral capsid protein, {sigma}3. This unusual binding interface produces high-avidity interactions between virus and receptor and likely primes early entry steps. NgR1 sequences engaged by reovirus also are required for NgR1 binding to ligands expressed by neurons and oligodendrocytes. These studies redefine models of reovirus cell-attachment and highlight the evolution of viruses to engage multiple receptors using distinct capsid components.

microbiology↗

Longitudinal changes in brain activation underlying reading fluency

Reading fluency - the speed and accuracy of reading connected text - is foundational to educational success. The current longitudinal study investigates the neural correlates of fluency development using a connected-text paradigm with an individualized presentation rate. Twenty-six children completed a functional MRI task in 1st/2nd grade (time 1) and again 1-2 years later (time 2). There was a longitudinal increase in activation in the ventral occipito-temporal (vOT) cortex from time 1 to time 2. This increase was also associated with improvements in reading fluency skills and modulated by individual speed demands. These findings highlight the reciprocal relationship of the vOT region with reading proficiency and its importance for supporting the developmental transition to fluent reading. These results have implications for developing effective interventions to target increased automaticity in reading.

neuroscience↗

Knowledge-based antibody repertoire simulation, a novel allele detection tool evaluation and application

Detailed knowledge of the diverse immunoglobulin germline genes is critical for the study of humoral immunity. Hundreds of alleles have been discovered by analyzing antibody repertoire sequencing (Rep-seq or Ig-seq) data via multiple novel allele detection tools (NADTs). However, the performance of these NADTs through antibody sequences with intrinsic somatic hypermutations (SHMs) is unclear. Here, we developed a tool to simulate repertoires by integrating the full spectrum features of an antibody repertoire such as germline gene usage, junctional modification, position-specific SHM and clonal expansion based on 2152 high-quality datasets. We then systematically evaluated these NADTs using both simulated and genuine Ig-seq datasets. Finally, we applied these NADTs to 687 Ig-seq datasets and identified 43 novel alleles using defined criteria. Twenty-five alleles were validated through findings of other sources. In addition to the novel alleles detected, our simulation tool, the results of our comparison, and the streamline of this process may benefit further humoral immunity studies via Ig-seq.

bioinformatics↗

5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes

5-methylcytosine (m5C) is an important epitranscriptomic modification involved in mRNA stability and translation efficiency in various biological processes. However, it remains unclear if m5C modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of Plasmodium parasites. Here, we characterize the landscape of m5C mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent (P. yoelii) and human (P. falciparum) malaria parasites. While different representations of m5C-modified mRNAs are associated with the different stages, the abundance of the m5C marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that m5C modifications confer stability to the Plasmodium transcripts and that a Plasmodium ortholog of NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Upon knock-out of P. yoelii nsun2 (pynsun2), marked reductions of m5C modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in rodent and human malaria parasites. Restoration of the nsun2 gene in the knock-out parasites rescued the gametocyte production phenotype as well as m5C modification of the gametocytogenesis-associated transcripts. Together with the mRNA m5C profiles for two species of Plasmodium, our findings demonstrate a major role for NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites. SignificanceModifications of RNA including methylations of cytosine (m5C) and adenosine (m6A) have important roles in RNA metabolism, cellular responses to stress, and biological processes of differentiation and development. Here, we report on the profiles of m5C mRNA modifications in malaria parasites that infect rodents (Plasmodium yoelii) and humans (Plasmodium falciparum). These parasites have genes that encode homologs of human and plant NSUN2 methyltransferases (m5C "writers"). We show that one of these homologs, termed PyNSUN2, stabilizes mRNA transcripts in P. yoelii and mediates m5C-associated development of the parasite sexual stages (gametocytes). Further research on m5C and other epitranscriptomic modifications may yield new insights into molecular pathways of gametocyte development and mosquito infectivity that can be exploited to interrupt malaria transmission.

microbiology↗

Drivers of Transcriptional Variance in Human Intestinal Epithelial Organoids

Background & AimsHuman intestinal epithelial organoids (enteroids and colonoids) are tissue cultures used for understanding the physiology of the intestinal epithelium. Here, we explored the effect on the transcriptome of common variations in culture methods, including extracellular matrix substrate, format, tissue segment, differentiation status, and patient heterogeneity. MethodsRNA-sequencing datasets from 251 experiments performed on 35 human enteroid and colonoid lines from 28 patients were aggregated from several groups in the Texas Medical Center. DESeq2 and Gene Set Enrichment Analysis (GSEA) was used to identify differentially expressed genes and enriched of pathways. ResultsPERMANOVA, Pearson correlations, and dendrogram analysis of all data indicated three tiers of influence of culture methods on transcriptomic variation: substrate (collagen vs. Matrigel) and format (3D, transwell, and monolayer) had the largest effect (7,271-1,305 differentially expressed genes-DEGs); segment of origin (duodenum, jejunum, ileum, colon) and differentiation status had a moderate effect (5,977-420 DEGs), and patient heterogeneity and specific experimental manipulations (e.g., pathogen infection) had the smallest effect. GSEA identified hundreds of pathways that varied between culture methods, such as IL1 cytokine signaling enriched in transwell vs. monolayer cultures, and cholesterol biosynthesis genes enriched in Matrigel vs. collagen cultures. ConclusionsSurprisingly large differences in organoid transcriptome were driven by variations in culture methods such as format and substrate, whereas experimental manipulations such as infection had modest effects. These results show that common variations in culture conditions can have large effects on intestinal organoids and should be accounted for when designing experiments and comparing results between laboratories. Our data constitute the largest RNA-seq dataset interrogating human intestinal organoids.

molecular biology↗

Nitric oxide synthase neurons in the preoptic hypothalamus are sleep-active and contribute to regulating NREM and REM sleep and lowering body temperature.

When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM active. This is the first instance of a predominantly NREM-active population in the PO area, or to our knowledge, elsewhere in the brain. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 hours, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer. In particular, mice were warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.

neuroscience↗

Single-cell epigenomic tracing of lifelong endothelial cell plasticity across mouse organs

Endothelial cells (ECs) across ages and tissues are highly heterogeneous in developmental origins, structures, functions, and cellular plasticity. Here, we applied CoBATCH for single-cell epigenomic tracing of dynamic EC lineage histories in five mouse organs from development to ageing. Our analyses showed that epigenomic memory reflects both developmental origins and tissue-restricted specialization of EC sublineages but with varying time lengths across organs. To gain insights into cellular plasticity of ECs, we identified bivalent chromatin occupancy of otherwise mutually exclusive EC- (ERG) and mesenchymal-specific (TWIST1/SNAI1) transcription factors promoting endothelial-to-mesenchymal transition. We further revealed that pseudotime trajectories by histone modifications H3K36me3 and H3K27ac faithfully recapitulate short- and long-range EC fate change over senescence, respectively. Together, our data provide a unique exploration of chromatin-level cell fate regulation of organotypic EC lineages across the lifespan. One-Sentence SummarySingle-cell chromatin binding is examined for tracing endothelial cell lineages in mouse organs across the lifespan.

genomics↗

SARS-CoV-2 receptor ACE2 identifies immuno-hot tumors in breast cancer

Angiotensin-converting enzyme 2 (ACE2) is known as a host cell receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is identified to be dysregulated in multiple tumors. Although the characterization of abnormal ACE2 expression in malignancies has been preliminarily explored, in-depth analysis of ACE2 in breast cancer (BRCA) has not been elucidated. A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). Next, correlations between ACE2 expression immunological characteristics in the BRCA tumor microenvironment (TME) were evaluated. Also, the role of ACE2 in predicting the clinical features and the response to therapeutic options in BRCA was estimated. These findings were subsequently validated in another public transcriptomic cohort as well as a recruited cohort. ACE2 was lowly expressed in most cancers compared with adjacent tissues. ACE2 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, immune checkpoints, and tumor mutation burden (TMB). Besides, high ACE2 levels indicated the triple-negative breast cancer (TNBC) subtype of BRCA, lower response to endocrine therapy and higher response to chemotherapy, anti-ERBB therapy, antiangiogenic therapy and immunotherapy. To sum up, ACE2 correlates with an inflamed TME and identifies immuno-hot tumors, which may be used as an auxiliary biomarker for the identification of immunological characteristics in BRCA.

immunology↗

Perfecting and extending the near-infrared biological window

In vivo fluorescence imaging in the second near-infrared window (NIR-II) has been considered as a promising technique for visualizing the mammals. However, the definition of the NIR-II region and the mechanism accounting for the excellent performance still need to be perfected. Herein, we simulated bioimaging in the NIR spectral range (to 2340 nm), confirmed the positive contribution of moderate light absorption by water in intravital imaging and perfected the NIR-II window as 900-1880 nm, where the 1400-1500 nm was defined as NIR-IIx region and the 1700-1880 nm was defined as NIR-IIc region, respectively. Moreover, the 2080-2340 nm was newly proposed as the third near-infrared (NIR-III) window, which was believed to provide the best imaging quality. The wide-field fluorescence microscopy in brain, in addition, was performed around NIR-IIx region with excellent optical sectioning strength and the largest imaging depth of in vivo NIR-II fluorescence microscopy to date. We also proposed 1400 nm long-pass detection in off-peak NIR-II imaging whose profits exceeded those of NIR-IIb imaging, using bright fluorophores with short peak emission wavelength.

bioengineering↗

Effects of straw returning with potassium fertilizer on the stem lodging resistance, grain quality and yield of spring maize (Zea mays L.)

The effects of straw returning with potassium fertilizer on the stem lodging resistance, grain quality and yield of spring maize were investigated to provide a scientific basis for the rational utilization of Inner Mongolia spring maize straw and potassium fertilizer resources. This study utilized Xianyu 335 as the test material, and a split plot design was carried out in three ecological regions from eastern to western Inner Mongolia (Tumochuan Plain irrigation area, Hetao Plain irrigation area and Lingnan warm dry zone), with the straw returning method as the main plot and potassium fertilizer dosage as the subplot. The stem resistance index, grain quality and yield were systematically identified. Both application of potassium fertilizer and straw returning improved the resistance and yield indicators of spring maize. Straw returning increased the effectiveness of potassium fertilizer application on spring maize plant height, ear height, fresh weight of stems, brix of stems and stem puncture strength by 2.82%-5.22%, 3.11%-5.90%, 15.96%-19.78%, 4.35%-4.50% and 8.89%-14.82%, respectively. Straw returning increased the effectiveness of potassium fertilizer application on the spring maize grain protein content, spring maize grain crude fat content, maize yield and yield variation coefficient by 3.49%-6.50%, 2.09%-4.43%, 4.87%-12.50% and 5.07%-7.55%, respectively. Straw returning can be combined with reasonable application of potassium fertilizer to increase the effectiveness of potassium fertilizer and enhance lodging resistance. Along with increased maize yield, straw returning also improves grain quality and enhances yield stability, providing a theoretical basis for high-yield and stress-resistant cultivation of Inner Mongolia spring maize, which can be popularized and applied in the spring maize planting areas of Inner Mongolia.

plant biology↗