Preoperative visit-care for transcatheter aortic valve replacement: a review.

AIM: The aim of this review is to evaluate and summarize the evidence for preoperative visit-care of transcatheter aortic valve replacement (TAVR) and to provide evidence-based support for clinical intervention. DESIGN: The review presents an evidence summary report, following the standard of the Fudan University Center for Evidence-based Nursing. METHODS: Literature related to preoperative visit-care for transcatheter aortic valve replacement have been retrieved based on the "6S" pyramid model of evidence. The types of literature included systematic reviews, expert consensus, evidence summary, and guidelines. DATA SOURCES: Up To Date, Cochrane Library, Joanna Briggs Institute, National Institute for Health and Care Excellence, Medlive, American Heart Association, Registered Nurses Association of Ontario, Scottish Intercollegiate Guidelines Network, European Society of Cardiology, American College of Cardiology, PubMed, CINAHL, Wanfang database, VIP database, Chinese biomedical literature database, CNKI. The search period is limited to the time when each database was established until February 2024. RESULTS: A total of 18 articles were included in this review, consisting of 1 systematic review, 1 evidence summary, 3 guidelines and 13 expert consensuses. This review summarized 30 pieces of the best evidence for preoperative visit-care for transcatheter aortic valve replacement, encompassing three evidence themes: multidisciplinary team collaboration, preoperative assessment, and preoperative education. CONCLUSION: The study has established an ideal foundation of evidence for preoperative visit-care in TAVR. However, throughout the particular application process, it was crucial to assess the feasibility and relevance of the evidence in clinical practice by taking into account elements such as the application setting, recommendations from experts with diverse expertise, and the preferences of the patients.

Preparation and characteristics of soy protein isolate - Sea buckthorn flavone emulsion and their effects of on quality and heterocyclic amines of roasted mutton granules.

A soy protein isolate (SPI) - sea buckthorn flavonoid emulsion was developed to study its effects on roasted lamb quality and heterocyclic amine (HAAs) precursors. The emulsion was stable with uniformly dispersed, well-encapsulated droplets averaging 0.1 to 10 µm. CLSM confirmed its good physical stability, small particle size, and uniform dispersion. FTIR the existence of hydrogen bond, hydrophobic interaction and physical adhesion between SPI and sea-buckthorn flavonoids. The emulsion improved lamb pellet texture by reducing chewiness and hardness, increasing adhesion, and decreasing browning. The emulsion-treated roasted mutton showed a 47.95-53.56 % increase in DPPH scavenging activity and MDA content reduction from 60.78 to 17.80 nmol/mg, indicating strong antioxidant activity and lipid oxidation inhibition. For both precursors and HAAs, there was a significant intensity of inhibition, where creatine decreased by about 44.91-68.34 %, glucose by 84.47 %-97.74 %, and the seven HAAs, Norharman, Harman, IQ, MeIQ, MeIQx, AαC, and PhIP, were inhibited by 79.64 %, respectively, 88.76 %, 65.07 %, 87.27 %, 96.16 %, 89.30 % and 49.44 %, respectively. This study aimed to develop a novel soy protein isolate-sea buckthorn flavonoid emulsion and evaluate its potential to improve roasted lamb quality while inhibiting the formation of harmful HAAs.

Induction of interleukin-6 by SPZ1-mediated Wnt5a signaling boosts progression of nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is a common malignancy in Southeast Asia, and in the Guangxi and Guangdong provinces of China. The spermatogenic transcription factor zip 1 (SPZ1) is a member of bHLH zip family, and promotes tumorigenesis in the liver, colon and breast tissues. However, the role of SPZ1 in the progression of NPC is unclear. In this study, we found that SPZ1 mRNA and protein levels were significantly upregulated in NPC tissues compared to the normal nasopharyngeal tissues. Furthermore, SPZ1 knockdown in NPC cell lines inhibited proliferation, epithelial-mesenchymal transition, migration, and invasion in vitro, and suppressed tumorigenesis in an in vivo model. On the other hand, SPZ1 overexpression facilitated the growth of NPC cells. Mechanistically, SPZ1-driven progression of NPC is dependent on the Wnt5a/interleukin-6 (IL-6) signaling pathway. Consistent with this, IL-6 levels were significantly increased in NPC tissues and correlated positively with SPZ1 expression. Taken together, our findings suggest that SPZ1 mediates NPC progression through Wnt5a/IL-6 signaling, and the SPZ1/Wnt5a/IL-6 axis is a potential therapeutic target for NPC.

Relationship between life's essential 8 and the risk of gestational diabetes among us adults.

OBJECTIVE: The purpose of this study is to explore the relationship between Life's Essential 8 (LE8) and the risk of gestational diabetes among US adults. METHOD: We used National Health and Nutrition Examination Surveys 2007-2018 data to perform this study. LE8 scores comprised 4 health behaviors (diet, physical activity, nicotine exposure, and sleep duration) and 4 health factors (BMI, non-high-density lipoprotein [HDL] cholesterol, blood glucose, and blood pressure). Then, LE8 were categorized into low CVH (0 to 49 scores), moderated CVH (50 to 79 scores), and high CVH (80 to 100 scores). Weighted multivariate Logistic regression analysis model were used to estimate the relationship between LE8 and gestational diabetes. RESULT: A total of 3,189 participants were included, and the portion of gestational diabetes was 15.33%, 11.46%, 7.71% in low CVH, moderate CVH, and high CVH, respectively. Adjustment for covariates, we found that high CVH (OR: 0.49, 95%CI: 0.29-0.83, p = 0.01) was associated with decreased of gestational diabetes, not moderate CVH (OR: 0.78, 95%CI: 0.50-1.20, p = 0.25). This inverse associations were dose-response dependent (p-nonlinear = 0.982). This inverse associations were significant in subgroup. Significant interaction between CVH and family diabetes with the risk of gestational diabetes was found (P for interaction = 0.04). High CVH (OR: 0.357, 95%CI: 0.176-0.724, p = 0.005) could significantly decrease the risk of gestational diabetes in the population with family diabetes. The results were generally robust in sensitivity analyses after excluding of ASCVD participants. CONCLUSION: The high CVH could decrease the risk of gestational diabetes, especially in the population of family diabetes.

Barriers and facilitators of the nurse providing evidence-based preoperative visit-care for transcatheter aortic valve replacement: a mixed-methods study based on an evidence application setting.

BACKGROUND: Preoperative visit-care for transcatheter aortic valve replacement (TAVR) plays a crucial role in improving the quality of care and patient safety. However, preoperative care for TAVR patients is still in its early stages in China, with the care often being experience-based. The application of relevant evidence in nursing practice is necessary. Little is known regarding the facilitators and barriers to apply and compliance to the evidences about preoperative visit-care for TAVR in nursing. METHODS: The Nurse's Compliance Checklist was used to investigate the evidence-based compliance of nurses (n = 21) who worked in the TAVR team in the evidence-based implementation setting. Meanwhile, an Evidence-Based Practice Beliefs Scale, and Influencing Factors Checklist were used to investigate all nurses (n = 66) who work in the same setting. Stakeholders (Middle and senior-level nursing administrators, frontline clinical nurses, and patients) interview was carried out to further disclose the barriers and facilitators in the process of evidence-based practice. RESULTS: The results of this study showed that only 1 evidence implemented fully (100%) by nurses, 3 evidences with 0% implementation rate, and implementation rate of the other evidences were 9.5∼71.4%. The overall score of nurses' evidence-based nursing belief level was (3.52 ± 0.82). Three domains of barriers were identified: the Context Domain included lack of nursing procedures, inadequate health education materials, insufficient training; the Practitioner Domain included insufficient attention, lack of relevant knowledge, high work pressure and uncertainty of expected results, and Patient Domain included lack of relational knowledge. Facilitating factors included leadership support, nurse' high evidence-based nursing belief, high executive ability and enthusiasm for learning. CONCLUSION: The study indicated that the nurses' compliance of evidence-based practice in preoperative visit-care for TAVR was in lower level. There were some factors influencing the application of the evidences. The study revealed potential modifiable barriers to the successful implementation of evidence-based preoperative visit-care, including a lack of preoperative visit- care routine, related knowledge and training. Leadership support and nurse training should be considered to improve nurses' compliance with evidence-based practice.

Developing and Validating of the Family Coping Scale for Patients with Chronic Heart Failure.

Background: : Family coping, as an essential part of family management of patients with chronic heart failure (CHF), is an important component of CHF interventions, affecting the health of patients, family members, and the whole family. It is necessary to understand the current situation of family coping in patients with CHF to facilitate the development of family interventions for patients with CHF. This study aims to develop and validate a tool for assessing the family coping scale for patients with CHF. Methods: The semi-structured interviews, expert consensus meetings, expert consultations, and item analysis were used to develop the initial scale. We employed classical test theory and exploratory factor analysis to scrutinize and refine the items in the scale. To validate the scale, we used confirmatory factor analysis to assess structural validity. We assessed internal consistency, and split-half reliability to ensure the scale's robustness and accuracy. Results: The FCS-CHF consisted of 24 items, including six dimensions: strategies for better management of CHF, psychological coping, substantial support by family members, emergency coping, overall heart failure awareness, and patients' health behavior. The results of confirmatory factor analysis showed that the scale fitted the data with well construct validity. The results of the confirmatory factor analysis for the overall goodness of fit indices for the fitted model were found to be acceptable for the scale. The scale demonstrates good reliability and validity, meeting the requirements of psychometrics. Conclusions: The FCS-CHF developed in this study is considered reliable and valid, which can measure family coping in patients with CHF and provide a basis for developing family coping enhancement strategies.

Spinal nerve transection-induced upregulation of KDM4A in the dorsal root ganglia contributes to the development and maintenance of neuropathic pain via promoting CCL2 expression in rats.

Studies indicate that the lysine-specific demethylase 4A (KDM4A), acts as a key player in neuropathic pain, driving the process through its involvement in promoting neuroinflammation. Emerging evidence reveals that C-C Motif Chemokine Ligand 2 (CCL2) participates in neuroinflammation, which plays an important role in the development and maintenance of neuropathic pain. However, it remains unclear if KDM4A plays a role in regulating CCL2 in neuropathic pain. This study found that following spinal nerve transection (SNT) of the lumbar 5 nerve root in rats, the expression of KDM4A and CCL2 increased in the ipsilateral L4/5 dorsal root ganglia (DRG). Injecting KDM4A siRNA into the DRGs of rats post-SNT resulted in a higher paw withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared to the KDM4A scRNA group. In addition, prior microinjection of AAV-EGFP-KDM4A shRNA also alleviates the decrease in PWT and PWL caused by SNT. Correspondingly, microinjection of AAV-EGFP-KDM4A shRNA subsequent to SNT reduced the established mechanical and thermal hyperalgesia. Furthermore, AAV-EGFP-KDM4A shRNA injection decreased the expression of CCL2 in DRGs. ChIP-PCR analysis revealed that increased binding of p-STAT1 with the CCL2 promoter induced by SNT was inhibited by AAV-EGFP-KDM4A shRNA treatment. These findings suggest that KDM4A potentially influences neuropathic pain by regulating CCL2 expression in DRGs.

FOXO3 Activates MFN2 Expression to Maintain the Autophagy Response in Cancer Cells Under Amino Acid Deprivation.

The lack of amino acids triggers the autophagic response. Some studies have shown such starvation conditions also induce mitochondrial fusion, revealing a close correlation between the two processes. Although Mitofusin-2 (MFN2) has been demonstrated to play a role in fusion regulation, its role in the autophagic response and the variables that activate MFN2 under stress remain unknown. In this investigation, we screened and confirmed that forkhead box protein O3 (FOXO3) participates in MFN2's expression during short periods of starvation. Luciferase reporter test proved that FOXO3 facilitates MFN2's transcription by binding to its promoter region, and FOXO3 downregulation directly depresses MFN2's expression. Consequently, inhibiting the FOXO3-MFN2 axis results in the loss of mitochondrial fusion, disrupting the normal morphology of mitochondria, impairing the degradation of substrates, and reducing autophagosome accumulation, ultimately leading to the blockage of the autophagy. In conclusion, our work demonstrates that the FOXO3-MFN2 pathway is essential for adaptive changes in mitochondrial morphology and cellular autophagy response under nutritional constraints.

A longitudinal assessment of factors affecting training transfer among new clinical nurse specialists.

Objective: This study aimed to explore the determinants influencing training transfer and evaluate how those factors change over time among nurses who graduated from clinical nurse specialist training to provide a theoretical basis for improving the training transfer of clinical nurse specialists (CNSs). Methods: A quantitative longitudinal survey with four rounds of data collection was utilized to measure the influencing aspects of training transfer from June 2018 to December 2019. A total of 46 new CNSs participated in this study, including 30 and 16 nurses receiving training programs for CNSs in Infusion, Wound and Ostomy. The factor influencing training transfer (FITT) questionnaire was used to collect data for the first month (time 1), the third month (time 2), the sixth month (time 3), and the first year (time 4) after training. This questionnaire contains 53 items divided into five dimensions, including managerial support (20 items); hindrance in the organization (6 items); the validity of the training program (10 items); organizational and personal facilitators (11 items); and personal attitudes towards training transfer (6 items). Results: The influencing factors of CNSs transfer decreased over time, with managerial support, hindrance in the organization, the validity of the training program, and personal attitudes towards training transfer changing statistically over time (P < 0.05), and no statistical difference in organizational and personal facilitators over time (P = 0.229). During early after training (the first month and the third month after training), hindrance in the organization is the biggest obstacle to training transfer. During the later of training (the sixth month and first year after the training), managerial support is the biggest obstacle to training transfer. Overall level of influencing factors of training transfer decreased in three months after training among Infusion nurses (P < 0.001), and Wound and Ostomy nurses decreased in the first year after training (P < 0.001). Conclusions: The trend and level of training transfer predictors decreased depending on time. Clarifying the factors influencing transfer and its patterns may help nursing managers enhance the implementation and impact of nurse specialist training.

Promoting γ-aminobutyric acid accumulation to enhances saline-alkali tolerance in tomato.

Saline-alkali stress is a widely distributed abiotic stress that severely limits plant growth. γ-Aminobutyric acid (GABA) accumulates rapidly in plants under saline-alkali stress, but the underlying molecular mechanisms and associated regulatory networks remain unclear. Here, we report a MYB-like protein, I-box binding factor (SlMYBI), which positively regulates saline-alkali tolerance through induced GABA accumulation by directly modulating the glutamic acid decarboxylase (GAD) gene SlGAD1 in tomato (Solanum lycopersicum L.). Overexpression of SlGAD1 increased GABA levels and decreased reactive oxygen species (ROS) accumulation under saline-alkali stress, while silencing of SlGAD1 further suggested that SlGAD1 plays an active role in GABA synthesis and saline-alkali tolerance of tomato. In addition, we found that SlMYBI activates SlGAD1 transcription. Both overexpression of SlMYBI and editing of SlMYBI using CRISPR/Cas9 showed that SlMYBI regulates GABA synthesis by modulating SlGAD1 expression. Furthermore, the interaction of SlNF-YC1 with SlMYBI enhanced the transcriptional activity of SlMYBI on SlGAD1 to further improve saline-alkali tolerance in tomato. Interestingly, we found that ethylene signaling was involved in the GABA response to saline-alkali stress by RNA-seq analysis of SlGAD1-overexpressing lines. This study elucidates the involvement of SlMYBI in GABA synthesis regulation. Specifically, the SlMYBI-SlNF-YC1 module is involved in GABA accumulation in response to saline-alkali stress.

Spatial Pattern of Living Woody and Coarse Woody Debris in Warm-Temperate Broad-Leaved Secondary Forest in North China.

The investigation into the spatial distribution of living woody (LWD) and coarse woody debris (CWD) within forests represents a fundamental methodology for probing the inherent mechanisms governing coexistence and mortality within forest ecosystems. Here, a complete spatial randomness (CSR) null model was employed to scrutinize the spatial pattern, while canonical correspondence analysis (CCA) and the Torus-translation test (TTT) were utilized to elucidate the distribution patterns of LWD and CWD within warm-temperate deciduous broadleaf secondary forests in Dongling Mountains plot, northern China. The results reveal that both LWD and CWD exhibit an aggregated distribution as the predominant pattern in the Dongling Mountains plot, with the proportion and intensity of aggregation diminishing as spatial scale increases. Specifically, the aggregation intensity g0-10 demonstrates a significant negative correlation with abundance and maximum diameter at breast height (DBH). Notably, the g0-10 of LWD manifests a stronger correlation with the maximum DBH, whereas the g0-10 of CWD exhibits a greater association with the mortality rate. CCA outcomes suggest that elevation, convexity, and aspect significantly impact LWD distribution, whereas CWD distribution shows substantial negative correlations with elevation, convexity, slope, and aspect. TTT findings indicate that ecosystems characterized by a substantial presence of LWD also display a notable prevalence of CWD. Additionally, the majority of species exhibit no habitat preference, displaying neutral habitat connections and low ecological niche differentiation within the sampled plot.

Reinvigoration of cytotoxic T lymphocytes in microsatellite instability-high colon adenocarcinoma through lysosomal degradation of PD-L1.

Compensation and intracellular storage of PD-L1 may compromise the efficacy of antibody drugs targeting the conformational blockade of PD1/PD-L1 on the cell surface. Alternative therapies aiming to reduce the overall cellular abundance of PD-L1 thus might overcome resistance to conventional immune checkpoint blockade. Here we show by bioinformatics analysis that colon adenocarcinoma (COAD) with high microsatellite instability (MSI-H) presents the most promising potential for this therapeutic intervention, and that overall PD-L1 abundance could be controlled via HSC70-mediated lysosomal degradation. Proteomic and metabolomic analyses of mice COAD with MSI-H in situ unveil a prominent acidic tumor microenvironment. To harness these properties, an artificial protein, IgP ß, is engineered using pH-responsive peptidic foldamers. This features customized peptide patterns and designed molecular function to facilitate interaction between neoplastic PD-L1 and HSC70. IgP ß effectively reduces neoplastic PD-L1 levels via HSC70-mediated lysosomal degradation, thereby persistently revitalizing the action of tumor-infiltrating CD8 + T cells. Notably, the anti-tumor effect of lysosomal-degradation-based therapy surpasses that of antibody-based immune checkpoint blockade for MSI-H COAD in multiple mouse models. The presented strategy expands the use of peptidic foldamers in discovering artificial protein drugs for targeted cancer immunotherapy.

Discovery of GuaB inhibitors with efficacy against Acinetobacter baumannii infection.

Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step in de novo guanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whether in vivo inhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial. Here, we describe the discovery of extremely potent small molecule GuaB inhibitors (GuaBi) specific to pathogenic bacteria with a low frequency of on-target spontaneous resistance and bactericidal efficacy in vivo against Acinetobacter baumannii mouse models of infection. The spectrum of GuaBi activity includes multidrug-resistant pathogens that are a critical priority of new antibiotic development. Co-crystal structures of A. baumannii, Staphylococcus aureus, and Escherichia coli GuaB proteins bound to inhibitors show comparable binding modes of GuaBi across species and identifies key binding site residues that are predictive of whole-cell activity across both Gram-positive and Gram-negative clades of Bacteria. The clear in vivo efficacy of these small molecule GuaB inhibitors in a model of A. baumannii infection validates GuaB as an essential antibiotic target. IMPORTANCE: The emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition of de novo guanine biosynthesis is bactericidal in a mouse model of Acinetobacter baumannii infection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections.

The Sweet Relationship between the Endometrium and Protein Glycosylation.

The endometrium is an important part of women's bodies for menstruation and pregnancy. Various proteins are widely expressed on the surface of endometrial cells, and glycosylation is an important post-translational modification of proteins. Glycosylation modification is closely related not only to endometrial receptivity but also to common diseases related to endometrial receptivity. Glycosylation can improve endometrial receptivity, promote embryo localization and trophoblast cell adhesion and invasion, and contribute to successful implantation. Two diseases related to endometrial receptivity include endometriosis and endometrial cancer. As a common benign disease in women, endometriosis is often accompanied by an increased menstrual volume, prolonged menstrual periods, progressive and aggravated dysmenorrhea, and may be accompanied by infertility. Protein glycosylation modification of the endometrial surface indicates the severity of the disease and may be an important pathogenesis of endometriosis. In cancer, glycosylation modifications on the surface of tumor cells can be a marker to distinguish the type and severity of endometrial cancer. This review highlights the role of protein glycosylation in embryo-maternal endometrial dialogue and explores its potential mechanisms in diseases related to endometrial receptivity, which could provide a new clinical approach for their diagnosis and treatment.

The efficacy of postoperative radiotherapy in resected pâ ¢A-N2 EGFR mutant and wild-type lung adenocarcinoma.

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Integrating Dynamic in vitro Systems and Mechanistic Absorption Modeling: Case Study of Pralsetinib.

Dynamic in vitro absorption systems and mechanistic absorption modeling via PBPK have both shown promise in predicting human oral absorption, although these efforts have been largely separate; this work aimed to integrate knowledge from these approaches to investigate the oral absorption of a RET inhibitor, pralsetinib, with BCS Class II properties. Tiny-TIM (TIM B.V., Weteringbrug​, The Netherlands) is a dynamic in vitro model with close simulation of the successive physiological conditions of the human stomach and small intestine. Tiny-TIM runs with pralsetinib were performed at doses of 200 mg and 400 mg under fasting conditions. Mechanistic modeling of absorption was performed in Simcyp V21 (Certara, Manchester, UK). Pralsetinib fasted bioaccessibility in the Tiny-TIM system was 63% at 200 mg and 53% at 400 mg; a 16% reduction at 400 mg was observed under elevated gastric pH. Maximum pralsetinib solubility from the small intestinal compartment in Tiny-TIM directly informed the supersaturation/precipitation model parameters. The PBPK model predicted a similar fraction absorbed at 200 mg and 400 mg, consistent with the dose proportional increases in observed pralsetinib exposure. Integrating dynamic in vitro systems with mechanistic absorption modeling provides a promising approach for understanding and predicting human absorption with challenging low solubility compounds.

Modular and Regioselective Synthesis of Benzo-Fused Five-Membered Rings Enabled by Co/Ti Synergism.

The regiocontrol in constructing benzo-fused five-membered rings by C-H cyclization remains an important challenge. We report a highly general and regioselective methodology to access such heterocycles and indenones, where under the catalysis of CoBr2/bipyridine, aryl titanates, alkynes and EX2 (E = NR, S(O), RP(O), R2Si, CO, etc.) were assembled to various heterocycles and indenones in a modular manner. Unprecedented 1,2-Co/Ti heterobimetallic arylene and benzotitanole intermediates have played crucial roles in these syntheses.

Identification and validation of two major QTL for grain number per spike on chromosomes 2B and 2D in bread wheat (Triticum aestivum L.).

KEY MESSAGE: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement.