Bacteriophage protein Gp46 is a cross-species inhibitor of nucleoid-associated HU proteins.

The architectural protein histone-like protein from Escherichia coli strain U93 (HU) is the most abundant bacterial DNA binding protein and highly conserved among bacteria and Apicomplexan parasites. It not only binds to double-stranded DNA (dsDNA) to maintain DNA stability but also, interacts with RNAs to regulate transcription and translation. Importantly, HU is essential to cell viability for many bacteria; hence, it is an important antibiotic target. Here, we report that Gp46 from bacteriophage SPO1 of Bacillus subtilis is an HU inhibitor whose expression prevents nucleoid segregation and causes filamentous morphology and growth defects in bacteria. We determined the solution structure of Gp46 and revealed a striking negatively charged surface. An NMR-derived structural model for the Gp46-HU complex shows that Gp46 occupies the DNA binding motif of the HU and therefore, occludes DNA binding, revealing a distinct strategy for HU inhibition. We identified the key residues responsible for the interaction that are conserved among HUs of bacteria and Apicomplexans, including clinically significant Mycobacterium tuberculosis, Acinetobacter baumannii, and Plasmodium falciparum, and confirm that Gp46 can also interact with these HUs. Our findings provide detailed insight into a mode of HU inhibition that provides a useful foundation for the development of antibacteria and antimalaria drugs.

Thermally Activated Photoluminescence Induced by Tunable Interlayer Interactions in Naturally Occurring van der Waals Superlattice SnS/TiS2.

van der Waals (vdW) superlattices, comprising different 2D materials aligned alternately by weak interlayer interactions, offer versatile structures for the fabrication of novel semiconductor devices. Despite their potential, the precise control of optoelectronic properties with interlayer interactions remains challenging. Here, we investigate the discrepancies between the SnS/TiS2 superlattice (SnTiS3) and its subsystems by comprehensive characterization and DFT calculations. The disappearance of certain Raman modes suggests that the interactions alter the SnS subsystem structure. Specifically, such structural changes transform the band structure from indirect to direct band gap, causing a strong PL emission (∼2.18 eV) in SnTiS3. In addition, the modulation of the optoelectronic properties ultimately leads to the unique phenomenon of thermally activated photoluminescence. This phenomenon is attributed to the inhibition of charge transfer induced by tunable intralayer strains. Our findings extend the understanding of the mechanism of interlayer interactions in van der Waals superlattices and provide insights into the design of high-temperature optoelectronic devices.

Probing wrapping dynamics of spherical nanoparticles by 3D vesicles using force-based simulations.

Nanoparticles present in various environments can interact with living organisms, potentially leading to deleterious effects. Understanding how these nanoparticles interact with cell membranes is crucial for rational assessment of their impact on diverse biological processes. While previous research has explored particle-membrane interactions, the dynamic processes of particle wrapping by fluid vesicles remain incompletely understood. In this study, we introduce a force-based, continuum-scale model utilizing triangulated mesh representation and discrete differential geometry to investigate particle-vesicle interaction dynamics. Our model captures the transformation of vesicle shape and nanoparticle wrapping by calculating the forces arising from membrane bending energy and particle adhesion energy. Inspired by cell phagocytosis of large particles, we focus on establishing a quantitative understanding of large-scale vesicle deformation induced by the interaction with particles of comparable sizes. We first examine the interactions between spherical vesicles and individual nanospheres, both externally and internally, and quantify energy landscapes across different wrapping fractions of the nanoparticles. Furthermore, we explore multiple particle interactions with biologically relevant fluid vesicles with nonspherical shapes. Our study reveals that initial particle positions and interaction sequences are critical in determining the final equilibrium shapes of the vesicle-particle complexes in these interactions. These findings emphasize the importance of nanoparticle positioning and wrapping fractions in the dynamics of particle-vesicle interactions, providing crucial insights for future research in the field.

Enumeration, Nomenclature, and Stability Rules of Carbon Nanobelts.

With recent breakthroughs and advances in synthetic chemistry, carbon nanobelts (CNBs) have become an emerging hot topic in chemistry and materials science. Owing to their unique molecular structures, CNBs have intriguing properties with applications in synthetic materials, host-guest chemistry, optoelectronics, and so on. Although a considerable number of CNBs with diverse forms have been synthesized, no systematic nomenclature is available yet for this important family of macrocycles. Moreover, little is known about the detailed isomerism of CNBs, which, in fact, exhibits greater complexity than that of carbon nanotubes. The copious variety of CNB isomers, along with the underlying structure-property relationships, bears fundamental relevance to the ongoing design and synthesis of novel nanobelts. In this paper, we propose an elegant approach to systematically enumerate, classify, and name all possible isomers of CNBs. Besides the simplest, standard CNBs defined by chiral indices (n, m), the nonstandard CNBs (n, m, l) involve an additional winding index l. Based on extensive quantum chemical calculations, we present a comprehensive study of the relative isomer stability of CNBs containing up to 30 rings. A simple Hückel-based model with a high predictive power reveals that the relative stability of standard CNBs is governed by the π stabilization and the strain destabilization induced by the cylindrical carbon framework, and the former effect prevails over the latter. For nonstandard CNBs, a third stability factor, the H···H repulsion in the benzo[c]phenanthrene-like motifs, is also shown to be important and can be incorporated into the simple quantitative model. In general, lower-energy CNB isomers have a larger HOMO-LUMO gap, suggesting that their thermodynamic stability coincides with kinetic stability. The most stable CNB isomers determined can be considered the optimal targets for future synthesis. These results lay an initial foundation and provide a useful theoretical tool for further research on CNBs and related analogues.

Generalized kekulenes and clarenes as novel families of cycloarenes: structures, stability, and spectroscopic properties.

Cycloarenes constitute a captivating class of polycyclic aromatic hydrocarbons with unique structures and properties, but their synthesis represents a challenging task in organic chemistry. Kekulenes and edge-extended kekulenes as classic types of cycloarenes play an important role in the comprehension of π electron distribution, but their sparse molecular diversity considerably limits their further development and application. In this work, we propose two novel classes of cycloarenes, the generalized kekulenes and the clarenes. Using density functional theory, we carry out a comprehensive study of all possible isomers of the generalized kekulenes and clarenes with different sizes. By applying a simple Hückel model, we show that π delocalization plays a crucial role in determining the relative stability of isomers. We also discover that π-π stacking is commonly present in certain larger clarenes and provides a considerable additional stabilization effect, making the corresponding isomers the lowest-energy ones. Among all considered typical looped polyarenes, generalized kekulenes and/or clarenes are revealed to be the energetically most stable forms, suggesting that these novel cycloarenes proposed here would be viable targets for future synthetic work. The simulated 1H NMR spectra and UV-vis absorption spectra provide valuable information about the electronic and optoelectronic properties for the most stable generalized kekulene and clarene species and may support their identification in future synthesis and experimental characterization.

Structurally diverse amides from Chloranthus henryi var. hupehensis and their anti-inflammatory activities by blocking Akt phosphorylation.

Eleven new amides, four racemic pairs of (±)-chlorahupetamides A, B, D, E (1, 2, 4, 5) and chlorahupetamides C, F, G (3, 6, 7), have been isolated from Chloranthus henryi var. hupehensis. Compounds 1-3 are the first naturally occurring dimers via an unprecedented [2 + 2] cycloaddition derived from two dissimilar cinnamic acid amides, while compounds 4 and 5 represent the first examples of lignanamides in Chloranthus; together with two new hydroxycinnamic acid amide monomers (6-7), these compounds were obtained. Their structures were characterized by nuclear magnetic resonance (NMR), electronic circular dichroism (ECD), and X-ray diffraction analysis. Meanwhile, an LPS-induced BV-2 cell inflammatory model was used to determine the potential anti-inflammatory activity of all the isolated compounds. Intriguingly, compound -1 treatment showed a much greater inhibition of TNF-α expression with an EC50 value of 1.80 µM, while compound + 1 had more advantages in reducing IL-1ß expression with an EC50 value of 19.93 µM. Moreover, compounds + 1 and -1 could significantly suppress inflammation and inhibit the Akt signaling pathway by decreasing the phosphorylated protein levels of Akt.

Discovery of sesquiterpenoids from the roots of Chloranthus henryi Hemsl. var. hupehensis (Pamp.) K. F. Wu and their anti-inflammatory activity by IKBα/NF-κB p65 signaling pathway suppression.

Phytochemical analysis of Chloranthus henryi var. hupehensis roots led to the identification of a new eudesmane sesquiterpenoid dimer, 18 new sesquiterpenoids, and three known sesquiterpenoids. Among the isolates, 1 was a rare sesquiterpenoid dimer that is assembled by a unique oxygen bridge (C11-O-C8') of two highly rearranged eudesmane-type sesquiterpenes with the undescribed C16 carbon framework. (+)-2 and (-)-2 were a pair of new skeleton dinorsesquiterpenoids with a remarkable 6/6/5 tricyclic ring framework including one γ-lactone ring and the bicyclo[3.3.1]nonane core. Their structures were elucidated using spectroscopic data, single-crystal X-ray diffraction analysis, and quantum chemical computations. In the LPS-induced BV-2 microglial cell model, 17 suppressed IL-1ß and TNF-α expression with EC50 values of 6.81 and 2.76 µM, respectively, indicating its excellent efficacy in inhibiting inflammatory factors production in a dose dependent manner and without cytotoxicity. In subsequent mechanism studies, compounds 3, 16, and 17 could reduce IL-1ß and TNF-α production by inhibiting IKBα/p65 pathway activation.

A High-Rigidity Organic-Inorganic Metal Halide Hybrid Enabling Reversible and Enhanced Self-Trapped Exciton Emission under High Pressure.

Zero-dimensional organic-inorganic metal halide hybrids provide ideal bulk-crystal platforms for exploring the pressure engineering of electron-phonon coupling (EPC) and self-trapped exciton (STE) emission at the molecular level. However, the low stiffness of inorganic clusters hinders the reversible tuning of these physical properties. Herein, we designed a Sb3+-doped metal halide with a high emission yield (89.4%) and high bulk modulus (35 GPa) that enables reversible and enhanced STE emission (20-fold) under pressure. The high lattice rigidity originates from the corner-shared cage-structured inorganic tetramers and ring-shaped organic ligands. Further, we reveal that the pressure-enhanced emission regime below 4.5 GPa is owing to the lattice hardening and preferably EPC strength reducing, while the pressure-insensitive emission regime within 4.5-8.5 GPa results from the enhanced intercluster Coulombic attraction force that resists intracluster compression. These results provide insights into the structure-property relation and molecular engineering of zero-dimensional metal halides toward wide-band and pressure-sensitive light sources.

Synthesis of ZSM-5 Zeolite Nanosheets with Tunable Silanol Nest Contents across an Ultra-wide pH Range and Their Catalytic Validation.

Zeolite synthesis under acidic conditions has always presented a challenge. In this study, we successfully prepared series of ZSM-5 zeolite nanosheets (Z-5-SCA-X) over a broad pH range (4 to 13) without the need for additional supplements. This achievement was realized through aggregation crystallization of ZSM-5 zeolite subcrystal (Z-5-SC) with highly short-range ordering and ultrasmall size extracted from the synthetic system of ZSM-5 zeolite. Furthermore, the crystallization behavior of Z-5-SC was investigated, revealing its non-classical crystallization process under mildly alkaline and acidic conditions (pH<10), and the combination of classical and non-classical processes under strongly alkaline conditions (pH≥10). What's particularly intriguing is that, the silanol nest content in the resultant Z-5-SCA-X samples appears to be dependent on the pH values during the Z-5-SC crystallization process rather than its crystallinity. Finally, the results of the furfuryl alcohol etherification reaction demonstrate that reducing the concentration of silanol nests significantly enhances the catalytic performance of the Z-5-SCA-X zeolite. The ability to synthesize zeolite in neutral and acidic environments without the additional mineralizing agents not only broadens the current view of traditional zeolite synthesis but also provides a new approach to control the silanol nest content of zeolite catalysts.

Infinitenes as the Most Stable Form of Cycloarenes: The Interplay among π Delocalization, Strain, and π-π Stacking.

The recent successful preparation of infinitene has sparked widespread attention due to its aesthetic appeal and synthetic challenge. Spectroscopic measurements and follow-up computational investigations suggest that infinitene holds fundamental significance and potential applications in chiroptics, optoelectronics, asymmetric synthesis, and supramolecular chemistry. However, unlike other looped polyarenes enriched with sizes and shapes, the infinitene molecule seems, so far, the only known example of this fascinating new form of nanocarbons, whose further exploitation would be considerably limited because of the lack of molecular diversity. Here, we introduce a whole new family of generalized infinitenes with different sizes and topologies. Three types of infinitene structures are rationally designed by joining two units of coronene, kekulene, or their extended analogs. The constructed molecules of varying sizes, each with a large number of possible topoisomers, are systematically studied by DFT calculations. Comprehensive analysis using a simple energy decomposition model uncovers that the stability of infinitenes is governed by the interplay among π delocalization, steric strain, and π-π stacking. While the first two factors are crucial to the stability of smaller infinitenes, the latter is the primary stabilizing interaction for larger infinitenes. Most importantly, we show that larger-sized infinitenes are actually the energetically most favorable form among all known looped polyarenes; their substantial thermodynamic stability surpassing that of circulenes, various carbon nanobelts, and kekulene-like macrocycles renders them promising targets for synthesis. The simulated 1H NMR, UV-vis, and circular dichroism spectra along with optical rotations for the most stable infinitene species may help their identification in future synthetic efforts.

Aerosol Jet Printing-Enabled Dual-Function Electrochemical and Colorimetric Biosensor for SARS-CoV-2 Detection.

An aerosol jet printing-enabled dual-function biosensor for the sensitive detection of pathogens using SARS-CoV-2 RNA as an example has been developed. A CRISPR-Cas13:guide-RNA complex is activated in the presence of a target RNA, leading to the collateral trans-cleavage of ssRNA probes that contain a horseradish peroxidase (HRP) tag. This, in turn, catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by HRP, resulting in a color change and electrochemical signal change. The colorimetric and electrochemical sensing protocol does not require complicated target amplification and probe immobilization and exhibits a detection sensitivity in the femtomolar range. Additionally, our biosensor demonstrates a wide dynamic range of 5 orders of magnitude. This low-cost aerosol inkjet printing technique allows for an amplification-free and integrated dual-function biosensor platform, which operates at physiological temperature and is designed for simple, rapid, and accurate point-of-care (POC) diagnostics in either low-resource settings or hospitals.

CRISPR-Cas12-based field-deployable system for rapid detection of synthetic DNA sequence of the monkeypox virus genome.

The global outbreak of the monkeypox virus (MPXV) highlights the need for rapid and cost-effective MPXV detection tools to effectively monitor and control the monkeypox disease. Herein, we demonstrated a portable CRISPR-Cas-based system for naked-eye detection of MPXV. The system harnesses the high selectivity of CRISPR-Cas12 and the isothermal nucleic acid amplification potential of recombinase polymerase amplification. It can detect both the current circulating MPXV clade and the original clades. We reached a limit of detection (LoD) of 22.4 aM (13.5 copies/µl) using a microtiter plate reader, while the visual LoD of the system is 75 aM (45 copies/µl) in a two-step assay, which is further reduced to 25 aM (15 copies/µl) in a one-pot system. We compared our results with quantitative polymerase chain reaction and obtained satisfactory consistency. For clinical application, we demonstrated a sensitive and precise visual detection method with attomolar sensitivity and a sample-to-answer time of 35 min.

Photoluminescent Properties and Mechanism of Novel Cyanine-Borondifluoride Curcuminoid Hybrids as Red-to-Near Infrared and Endoplasmic Reticulum-Targeting Dyes.

Synthesis-oriented design led us to the discovery of a series of novel cyanine-borondifluoride curcuminoid hybrids called Nanchang Red (NCR) dyes that overcome the intrinsic low synthetic yields of symmetrical cyanine-difluoroboronate (BF2 )-hybridized NIR dyes. The hybridization endows NCR dyes with high molar extinction coefficients, efficient red-to-NIR emission, and enlarged Stokes shifts. Quantum chemical calculations revealed that the asymmetrical layout of the three key electron-withdrawing and electron-donating fragments results in a special pattern of partial charge separation and inconsistent degrees of charge delocalization on their π-conjugated backbones. While the nature of the hemicyanine fragment exerts significant influence on the excitation modes of NCR dyes, the borondifluoride hemicurcuminoid fragment is the major contributor to the enlarged Stokes shifts. Cell imaging experiments illustrated that a subtle change in the N-heterocycle of the hemicyanine fragment has a remarkable effect on the subcellular localization of NCR dyes. Unlike other previously reported cyanine-BF2 hybridized dyes, which mainly target mitochondria, the benzothiazole and indole-based NCR dyes accumulate in both the endoplasmic reticulum (ER) and lipid droplets of HeLa cells, whereas the benzoxazole and quinoline-based NCR dyes stain the ER specifically.

Multi-Mode Photoluminescence Regulation in a Zero-Dimensional Organic-Inorganic Hybrid Metal Halide Perovskite─[(CH3)4N]2SnCl6.

Metal ion-doped zero-dimensional halide perovskites provide good platforms to generate broadband emission and explore the fundamental dynamics of emission regulations. Recently, Sb3+-doped zero-dimensional halide perovskites have attracted considerable attention for the high quantum yield of yellow emission; however, the triplet state recombination is activated and the singlet state emission is usually absent. Herein, we fabricate an Sb3+-doped zero-dimensional [(CH3)4N]2SnCl6 perovskite that can induce singlet and triplet emission. Density functional theory calculation shows that there are some overlaps between the highest occupied molecular orbitals and the lowest unoccupied molecular orbitals, which may induce a large energy separation between the lowest excited triplet states (T1) and the lowest excited singlet states (S1) [ΔE(S1 - T1)], impeding all the carriers' transfer from the singlet state to the triplet state. As a result, the reserved singlet emission together with the triplet emission can be regulated by excitation wavelength in situ. In addition, different Bi3+ ratios are co-doped into Sb3+@[(CH3)4N]2SnCl6, resulting in a photoluminescence ex situ regulation. Single-phase white light LED and optical anti-counterfeiting are developed further.

Supramolecular-Interactions-Modulated Photoluminescence in Indium Bromide-Based Isomers.

Here, two isomeric ionic zero-dimensional indium bromide crystals of α (1)/ß (2)-[OPy][InBr4(Phen)] (OPy = N-octylpyridinium; Phen = 1,10-phenanthroline) have been isolated simply by changing the cooling conditions in solvothermal syntheses. Structural comparisons indicate their different supramolecular interactions, which can be confirmed by Hirshfeld surface analyses. The crystal 2 has additional hydrogen bonds and π-π interactions; as a result, the more compact stacking of 2 could result in a 10-fold higher photoluminescence (PL) quantum yield (PLQY) than that of 1. Density functional theory calculations confirm the electron transition from the inorganic moiety to the organic ligand, which provides a further understanding of the optical process. This work provides a new idea for designing PL indium-based halides by understanding the structure-PL relationship.

Mussel-Inspired Two-Dimensional Halide Perovskite Facilitated Dopamine Polymerization and Self-Adhesive Photoelectric Coating.

Polydopamine (PDA) is a good adhesion agent for lots of gels inspired by the mussel, whereas hybrid organic-inorganic perovskites (HOIPs) usually exhibit extraordinary optoelectronic performance. Herein, mussel-inspired chemistry has been integrated with two-dimensional HOIPs first, leading to the preparation of new crystal (HDA)2PbBr4 (1) (DA = dopamine). The organic cation dopamine can be introduced into PDA resulting in a thin film of (HPDA)2PbBr4 (PDA-1). The dissolved inorganic components of layered perovskite in DMF solution together with H2O2 addition can facilitate DA polymerization greatly. More importantly, PDA-1 can inherit an excellent semiconductor property of HOIPs and robust adhesion of the PDA hydrogel resulting in a self-adhesive photoelectric coating on various interfaces.

Development and validation of an HPLC coupled with tandem mass spectrometry method for the determination of HSK7653, a novel super long-acting dipeptidyl peptidase-4 inhibitor, in human plasma and urine and its application to a pharmacokinetic study.

HSK7653 is a novel super long-acting dipeptidyl peptidase-4 inhibitor, which is promising for the treatment of type 2 diabetes mellitus with the twice-monthly dosing regimen. In this article, a robust and sensitive HPLC coupled with tandem mass spectrometry method for determining the concentration of HSK7653 in human plasma and urine was developed and validated for the first time. Plasma and urine samples were prepared by protein precipitation. After that, the extracts were analyzed using an LC-20A HPLC system coupled with API 4000 tandem MS equipped with an electrospray ionization source in positive mode. Separation was obtained using an XBridge Phenyl column (2.1 × 50 mm, 3.5 µm) with a gradient elution of acetonitrile and water containing 0.1% formic acid and 5% acetonitrile at room temperature. This bioanalysis method has been fully validated and the results showed good sensitivity and specificity. In brief, the standard curves were linear over the concentration range of 2.00-2000 ng/ml for plasma and 20.0-20,000 ng/ml for urine, respectively. In addition, the precisions of inter- and intra-run of HSK7653 were less than 12.7% and the accuracies were -3.3% to 6.3% for both plasma and urine. Finally, this method was successfully applied to explore the pharmacokinetic characteristics of HSK7653 in Chinese healthy volunteers in a first-in-human study.

An Optimization Method of Production-Distribution in Multi-Value-Chain.

Value chain collaboration management is an effective means for enterprises to reduce costs and increase efficiency to enhance competitiveness. Vertical and horizontal collaboration have received much attention, but the current collaboration model combining the two is weak in terms of task assignment and node collaboration constraints in the whole production-distribution process. Therefore, in the enterprise dynamic alliance, this paper models the MVC (multi-value-chain) collaboration process for the optimization needs of the MVC collaboration network in production-distribution and other aspects. Then a MVC collaboration network optimization model is constructed with the lowest total production-distribution cost as the optimization objective and with the delivery cycle and task quantity as the constraints. For the high-dimensional characteristics of the decision space in the multi-task, multi-production end, multi-distribution end, and multi-level inventory production-distribution scenario, a genetic algorithm is used to solve the MVC collaboration network optimization model and solve the problem of difficult collaboration of MVC collaboration network nodes by adjusting the constraints among genes. In view of the multi-level characteristics of the production-distribution scenario, two chromosome coding methods are proposed: staged coding and integrated coding. Moreover, an algorithm ERGA (enhanced roulette genetic algorithm) is proposed with enhanced elite retention based on a SGA (simple genetic algorithm). The comparative experiment results of SGA, SEGA (strengthen elitist genetic algorithm), ERGA, and the analysis of the population evolution process show that ERGA is superior to SGA and SEGA in terms of time cost and optimization results through the reasonable combination of coding methods and selection operators. Furthermore, ERGA has higher generality and can be adapted to solve MVC collaboration network optimization models in different production-distribution environments.

Using Zebrafish Animal Model to Study the Genetic Underpinning and Mechanism of Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is largely an autosomal dominant genetic disorder manifesting fibrofatty infiltration and ventricular arrhythmia with predominantly right ventricular involvement. ACM is one of the major conditions associated with an increased risk of sudden cardiac death, most notably in young individuals and athletes. ACM has strong genetic determinants, and genetic variants in more than 25 genes have been identified to be associated with ACM, accounting for approximately 60% of ACM cases. Genetic studies of ACM in vertebrate animal models such as zebrafish (Danio rerio), which are highly amenable to large-scale genetic and drug screenings, offer unique opportunities to identify and functionally assess new genetic variants associated with ACM and to dissect the underlying molecular and cellular mechanisms at the whole-organism level. Here, we summarize key genes implicated in ACM. We discuss the use of zebrafish models, categorized according to gene manipulation approaches, such as gene knockdown, gene knock-out, transgenic overexpression, and CRISPR/Cas9-mediated knock-in, to study the genetic underpinning and mechanism of ACM. Information gained from genetic and pharmacogenomic studies in such animal models can not only increase our understanding of the pathophysiology of disease progression, but also guide disease diagnosis, prognosis, and the development of innovative therapeutic strategies.

Identification and Validation of a Stable Major-Effect Quantitative Trait Locus for Kernel Number per Spike on Chromosome 2D in Wheat (Triticum aestivum L.).

A recombinant inbred line population including 371 lines was developed by a high kernel number per spike (KNPS) genotype T1208 and a low KNPS genotype Chuannong18 (CN18). A genetic linkage map consisting of 11,583 markers was constructed by the Wheat55K SNP Array. The quantitative trait loci (QTLs) related to KNPS were detected in three years. Eight, twenty-seven, and four QTLs were identified using the ICIM-BIP, ICIM-MET, and ICIM-EPI methods, respectively. One QTL, QKnps.sau-2D.1, which was mapped on chromosome 2D, can explain 18.10% of the phenotypic variation (PVE) on average and be considered a major and stable QTL for KNPS. This QTL was located in a 0.89 Mb interval on chromosome 2D and flanked by the markers AX-109283238 and AX-111606890. Moreover, KASP-AX-111462389, a Kompetitive Allele-Specific PCR (KASP) marker which closely linked to QKnps.sau-2D.1, was designed. The genetic effect of QKnps.sau-2D.1 on KNPS was successfully confirmed in two RIL populations. The results also showed that the significant increase of KNPS and 1000-kernel weight (TKW) was caused by QKnps.sau-2D.1 overcoming the disadvantage due to the decrease of spike number (SN) and finally lead to a significant increase of grain yield. In addition, within the interval in which QKnps.sau-2D.1 is located in Chinese Spring reference genomes, only fifteen genes were found, and two genes that might associate with KNPS were identified. QKnps.sau-2D.1 may provide a new resource for the high-yield breeding of wheat in the future.