Pyridaben inhibits cell cycle progression and delays early embryonic development in zebrafish (Danio rerio).

Pyridaben is a broad-spectrum, contact-killing acaricide that can be used to control a variety of harmful food and plant mites. Pyridaben displays cardiotoxicity and liver toxicity toward fish, but the effects on fish embryonic development have not been characterized. We exposed early zebrafish embryos to 20, 30, and 40 µg/L concentrations of pyridaben. The exposure caused developmental abnormalities, including delayed embryonic shield formation, yolk sac resorption, decreases in body length, reduced pigmentation, and delays in hatching. Pyridaben caused a significant increase in the transcription level of the endoderm marker foxa2, but the transcription levels of the ectoderm development marker foxb1a and the mesoderm development marker snaila were not significantly altered. The transcription levels of the genes SOX17 in early embryos were significantly reduced. After exposure to pyridaben, catalase (CAT) activity and glutathione (GSH) content were increased, and cyclin D1, that is involved in early embryonic development, was abnormally expressed. This study shows that pyridaben causes anomalous development in zebrafish embryos by interfering with the cell cycle order of early embryonic development and inducing excessive oxidative stress. Colivelin, an agonist of the STAT3 signaling pathway, acted as a salvage drug to restore the cell cycle order during embryonic development following exposure to pyridaben. Thus, the toxic effects may be caused by pyridaben's regulation of the STAT3 signaling pathway.

The prognostic value of controlling nutritional status score on esophageal squamous cell carcinoma patients with neoadjuvant therapy followed by esophagectomy-a retrospective research.

Background: A variety of nutritional evaluation parameters has been documented as prognostic indicators in some malignancies. However, the prognostic significance of the controlling nutritional status (CONUT) score, as one of these nutritional indices, in patients with esophageal squamous cell carcinoma (ESCC) remains unclear and warrants investigation. Our study sought to elucidate the prognostic value of this nutritional index in ESCC patients who underwent neoadjuvant therapy followed by esophagectomy. Methods: This retrospective study encompassed 314 patients diagnosed with ESCC who underwent neoadjuvant therapy followed by esophagectomy at West China Hospital of Sichuan University between August 2016 and August 2021. CONUT scores were computed at two specific time points: prior to neoadjuvant therapy initiation and before surgery, utilizing serum albumin, total lymphocyte, and cholesterol levels of ESCC patients. Furthermore, the delta CONUT (ΔCONUT) score was derived by subtracting the preoperative CONUT score from the pretreatment CONUT score. The associations between CONUT scores and various survival outcomes were evaluated using Kaplan-Meier methods and Cox regression analysis. Results: Patients with a high preoperative CONUT score demonstrated a higher postoperative complication rate [odds ratio (OR) =2.009, 95% confidence interval (CI): 1.150-3.510, P=0.01] compared to those in the low CONUT group. Multivariate analysis revealed that a ΔCONUT score ≥0 served as an independent negative prognostic indicator for increased postoperative complications (OR =3.008, 95% CI: 1.509-5.999, P=0.002) and poorer overall survival [hazard ratio (HR) =2.388, 95% CI: 1.052-5.422, P=0.04] in ESCC patients who underwent neoadjuvant therapy combined with esophagectomy. Conclusions: A high preoperative CONUT score and a ΔCONUT score ≥0 were indicative of a poor prognostic nutritional status in ESCC patients who had undergone neoadjuvant therapy followed by esophagectomy.

[Essential roles of fibroblast growth factors in male reproduction].

The testis serves as the reproductive gland in male mammals, primarily tasked with the production of sperm and synthesis of androgens. A complex signaling network consisting of various cell types, including germ cells, Sertoli cells, and Leydig cells, supports the structure and maintains the function of the testis. Apart from the hypothalamic-pituitary-gonadal axis, various sex hormones and cytokines are also implicated in the regulation of testicular function. The fibroblast growth factor (FGF) represents a crucial class of active cytokines that stimulate cell proliferation, induce tissue differentiation, and govern organ development. This review summarizes the molecular mechanisms of FGF regulating testicular development and spermatogenesis and maintaining male fertility.

A comprehensive whole genome database of ethnic minority populations.

China, is characterized by its remarkable ethnical diversity, which necessitates whole genome variation data from multiple populations as crucial tools for advancing population genetics and precision medical research. However, there has been a scarcity of research concentrating on the whole genome of ethnic minority groups. To fill this gap, we developed the Guizhou Multi-ethnic Genome Database (GMGD). It comprises whole genome sequencing data from 476 healthy unrelated individuals spanning 11 ethnic minorities groups in Guizhou Province, Southwest China, including Bouyei, Dong, Miao, Yi, Bai, Gelo, Zhuang, Tujia, Yao, Hui, and Sui. The GMGD database comprises more than 16.33 million variants in GRCh38 and 16.20 million variants in GRCh37. Among these, approximately 11.9% (1,956,322) of the variants in GRCh38 and 18.5% (3,009,431) of the variants in GRCh37 are entirely new and do not exist in the dbSNP database. These novel variants shed light on the genetic diversity landscape across these populations, providing valuable insights with an average coverage of 5.5 ×. This makes GMGD the largest genome-wide database encompassing the most diverse ethnic groups to date. The GMGD interactive interface facilitates researchers with multi-dimensional mutation search methods and displays population frequency differences among global populations. Furthermore, GMGD is equipped with a genotype-imputation function, enabling enhanced capabilities for low-depth genomic research or targeted region capture studies. GMGD offers unique insights into the genomic variation landscape of different ethnic groups, which are freely accessible at https://db.cngb.org/pop/gmgd/ .

Erratum: Author correction to 'FGF4 protects the liver from immune-mediated injury by activating CaMKKß-PINK1 signal pathway to inhibit hepatocellular apoptosis' [Acta Pharm Sin B 14 (2024) 1605-1623].

[This corrects the article DOI: 10.1016/j.apsb.2023.12.012.].

Synthesis and Anti-gastric Cancer Activity by Targeting FGFR1 Pathway of Novel Asymmetric Bis-chalcone Compounds.

BACKGROUP: Bis-chalcone compounds with symmetrical structures, either isolated from natural products or chemically synthesized, have multiple pharmacological activities. Asymmetric Bis-chalcone compounds have not been reported before, which might be attributed to the synthetic challenges involved, and it remains unknown whether these compounds possess any potential pharmacological activities. AIMS: The aim of this study is to investigate the synthesis route of asymmetric bis-chalcone compounds and identify potential candidates with efficient anti-tumor activity. METHOD: The two-step structural optimization of the bis-chalcone compounds was carried out sequentially, guided by the screening of the compounds for their growth inhibitory activity against gastric cancer cells by MTT assay. The QSAR model of compounds was established through random forest (RF) algorithm. The activities of the optimal compound J3 on growth inhibition, apoptosis, and apoptosis-inducing protein expression in gastric cancer cells were investigated sequentially by colony formation assay, flow cytometry, and western blotting. Further, the inhibitory effects of J3 on the FGFR1 signaling pathway were explored by Wester Blotting, siRNA, and MTT assays. Finally, the in vivo anti-tumor activity and mechanism of J3 were studied through nude mouse xenograft assay, western blotting. RESULT: 27 asymmetric bis-chalcone compounds, including two types (N and J) were sequentially designed and synthesized. Some N-class compounds have good inhibitory activity on the growth of gastric cancer cells. The vast majority of J-class compounds optimized on the basis of N3 exhibit excellent inhibitory activity on gastric cancer cell growth. We established a QSAR model (R2 = 0.851627) by applying random forest algorithms. The optimal compound J3, which has better activity, concentration-dependently inhibited the formation of gastric cancer cell colonies and led to cell apoptosis by inducing the expression of the pro-apoptotic protein cleaved PARP. J3 may exert anti-gastric cancer effects by inhibiting the activation of FGFR1/ERK pathway. Moreover, at a dose of 10 mg/kg/day, J3 inhibited tumor growth in nude mice by nearly 70% in vivo with no significant toxic effect on body weight and organs. CONCLUSION: In summary, this study outlines a viable method for the synthesis of novel asymmetric bischalcone compounds. Furthermore, the compound J3 demonstrates substantial promise as a potential candidate for an anti-tumor drug.

Zedoary turmeric oil injection ameliorates lung inflammation via platelet factor 4 and regulates gut microbiota disorder in respiratory syncytial virus-infected young mice.

BACKGROUND: Respiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear. PURPOSE: The present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism. STUDY DESIGN AND METHODS: Lung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria. RESULTS: In the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota. CONCLUSION: ZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.

Substitute or coexistence? mediastinoscopy-assisted versus thoracoscope-assisted esophagectomy in esophageal cancer - a meta-analysis of perioperative outcomes and long-term survival.

BACKGROUND: Currently, mediastinoscopy-assisted esophagectomy (MAE) and thoracoscope-assisted esophagectomy (TAE) represent two prevalent forms of minimally invasive esophagectomy extensively employed in the management of esophageal cancer (EC). The aim of this meta-analysis is to assess and compare these two surgical approaches concerning perioperative outcomes and long-term survival, offering valuable insights for refining surgical strategies and enhancing patient outcomes in this field. METHODS: Adhering to PRISMA guidelines, we systematically searched PubMed, Web of Science, Cochrane Library, Embase, and CNKI databases until March 1, 2024, for studies comparing MAE and TAE. Outcomes of interest included perioperative outcomes (intraoperative outcomes, postoperative recovery, postoperative complications) and survival rates. Statistical analyses were performed using RevMan 5.4, with heterogeneity dictating the use of fixed or random-effects models. RESULTS: Totally 21 relevant studies were finally included. MAE was associated with significantly shorter operation times ((MD=-59.58 min, 95% CI: -82.90, -36.26) and less intraoperative blood loss (MD=-68.34 mL, 95% CI: -130.45, -6.23). However, MAE resulted in fewer lymph nodes being dissected (MD=-3.50, 95% CI: -6.23, -0.78). Postoperative recovery was enhanced following MAE, as evidenced by reduced hospital stays and tube times. MAE significantly reduced pulmonary complications (OR=0.59, 95% CI: 0.44, 0.81) but increased the incidence of recurrent laryngeal nerve injury (OR=1.84, 95% CI: 1.30, 2.60). No significant differences were observed in anastomotic leakage, chylothorax, cardiac complications, wound infections, and gastric retention between MAE and TAE. The long-term survival outcomes showed no statistical difference (HR=1.05, 95% CI: 0.71-1.54). CONCLUSIONS: MAE offers advantages in reducing operation time, blood loss, and specific postoperative complications, particularly pulmonary complications, with a shorter recovery period compared to TAE. However, it poses a higher risk of recurrent laryngeal nerve injury and results in fewer lymph nodes being dissected. No difference in long-term survival was observed, indicating that both techniques have distinct benefits and limitations. These findings underscore the need for personalized surgical approaches in EC treatment, considering individual patient characteristics and tumor specifics.

HLAIImaster: a deep learning method with adaptive domain knowledge predicts HLA II neoepitope immunogenic responses.

While significant strides have been made in predicting neoepitopes that trigger autologous CD4+ T cell responses, accurately identifying the antigen presentation by human leukocyte antigen (HLA) class II molecules remains a challenge. This identification is critical for developing vaccines and cancer immunotherapies. Current prediction methods are limited, primarily due to a lack of high-quality training epitope datasets and algorithmic constraints. To predict the exogenous HLA class II-restricted peptides across most of the human population, we utilized the mass spectrometry data to profile >223 000 eluted ligands over HLA-DR, -DQ, and -DP alleles. Here, by integrating these data with peptide processing and gene expression, we introduce HLAIImaster, an attention-based deep learning framework with adaptive domain knowledge for predicting neoepitope immunogenicity. Leveraging diverse biological characteristics and our enhanced deep learning framework, HLAIImaster is significantly improved against existing tools in terms of positive predictive value across various neoantigen studies. Robust domain knowledge learning accurately identifies neoepitope immunogenicity, bridging the gap between neoantigen biology and the clinical setting and paving the way for future neoantigen-based therapies to provide greater clinical benefit. In summary, we present a comprehensive exploitation of the immunogenic neoepitope repertoire of cancers, facilitating the effective development of "just-in-time" personalized vaccines.

Myocardial infarction accelerates the progression of MASH by triggering immunoinflammatory response and induction of periosti.

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD), especially advanced metabolic dysfunction-associated steatohepatitis (MASH), have an increased risk of cardiovascular diseases (CVDs). Whether CVD events will, in turn, influence the pathogenesis of MASLD remains unknown. Here, we show that myocardial infarction (MI) accelerates hepatic pathological progression of MASLD. Patients with MASLD who experience CVD events after their diagnosis exhibit accelerated liver fibrosis progression. MI promotes hepatic fibrosis in mice with MASH, accompanied by elevated circulating Ly6Chi monocytes and their recruitment to damaged liver tissues. These adverse effects are significantly abrogated when deleting these cells. Meanwhile, MI substantially increases circulating and cardiac periostin levels, which act on hepatocytes and stellate cells to promote hepatic lipid accumulation and fibrosis, finally exacerbating hepatic pathological progression of MASH. These preclinical and clinical results demonstrate that MI alters systemic homeostasis and upregulates pro-fibrotic factor production, triggering cross-disease communication that accelerates hepatic pathological progression of MASLD.

Rice-crayfish farming system promote subsoil microbial residual carbon accumulation and stabilization by mediating microbial metabolism process.

Rice-crayfish farming systems (RCs) can help mitigate climate change by enhancing soil organic carbon (SOC) sequestration. However, the mechanisms that govern the responses of microbial residues carbon (MRC), a key component of SOC, in RCs are not fully understood. We conducted a 6-year field experiment comparing RCs and rice monoculture systems (RMs). Specifically, we explored how MRC formation and stabilization differ between the two systems and how those differences are linked to changes in the metabolic processes of microbes. Results showed that MRC levels in RCs were 5.2 % and 40.0 % higher in the topsoil and subsoil, respectively, compared to RMs, indicating depth-dependent effects. Notably, MRC accumulation and stabilization in RCs were promoted through a cascade of processes of dissolved organic carbon (DOC) accessibility-microbial metabolism-mineral protection. In addition, the mechanism of MRC accumulation in subsoil differed between the two systems. Specifically, RMs improved accessibility of DOC by reducing humification and aromaticity of subsoil DOC, which helped microbes access to resources at lower cost. This decreased the respiration rate of microbes, thereby increasing microbial carbon pump (MCP) efficiency and thus promoting MRC accumulation. By contrast, the crayfish in RCs facilitated carbon exchange between topsoil and subsoil through their burrowing behaviors. This increased carbon allocation for microbial metabolism in the subsoil, supporting a larger microbial population and thus enhancing the MCP capacity, while reducing MRC re-decomposition via enhanced mineral protection, further increasing subsoil MRC accumulation. That is, MRC accumulation in the subsoil of RCs was predominantly driven by microbial population numbers (MCP capacity) whereas that of RMs was mostly driven by microbial anabolic efficacy (MCP efficiency). Our findings reveal a key mechanism by which RCs promoted soil MRC accumulation and stabilization, highlighting the potential role of DOC accessibility-microbial metabolism-mineral protection pathway in regulating MRC accumulation and stabilization.

Heterojunction of branched benzopyrazine-based polymers coating on graphene for electrochemical sensing of vanillin.

Vanillin finds widespread applications in various industries, such as food, pharmaceuticals, and cosmetics. However, excessive intake of vanillin could pose risks to human health. This study detailed the successful creation of a heterojunction of branched benzopyrazine-based polymers coating on graphene (CMP-rGO) through the Sonogashira-Hagihara coupling reaction. Utilizing the CMP-rGO, a novel electrochemical sensor for vanillin detection was developed. Besides, the synthesized materials were validated using standard characterization techniques. Both cyclic voltammetry and differential pulse voltammetry techniques were employed to investigate vanillin's electrochemical characteristics on this sensor. The findings indicated a significant enhancement in vanillin's electrochemical signal responsiveness with the application of CMP-rGO. Under optimal conditions, the sensor demonstrated a linear response to vanillin concentrations ranging from 0.08 to 33 µM and achieved a detection limit as low as 0.014 µM. Also, the constructed electrochemical sensor exhibited excellent selectivity, stability, and reproducibility. It has been effectively employed to detect vanillin in real samples such as human serum, human urine, and vanillin tablets, with a recovery rate of 99.13-103.6 % and an RSD of 3.46-1.26 %. Overall, this innovative sensor offers a novel approach to the efficient and convenient detection of vanillin.

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.

The Carthamus tinctorius L. genome sequence provides insights into synthesis of unsaturated fatty acids.

Domesticated safflower (Carthamus tinctorius L.) is a widely cultivated edible oil crop. However, despite its economic importance, the genetic basis underlying key traits such as oil content, resistance to biotic and abiotic stresses, and flowering time remains poorly understood. Here, we present the genome assembly for C. tinctorius variety Jihong01, which was obtained by integrating Oxford Nanopore Technologies (ONT) and BGI-SEQ500 sequencing results. The assembled genome was 1,061.1 Mb, and consisted of 32,379 protein-coding genes, 97.71% of which were functionally annotated. Safflower had a recent whole genome duplication (WGD) event in evolution history and diverged from sunflower approximately 37.3 million years ago. Through comparative genomic analysis at five seed development stages, we unveiled the pivotal roles of fatty acid desaturase 2 (FAD2) and fatty acid desaturase 6 (FAD6) in linoleic acid (LA) biosynthesis. Similarly, the differential gene expression analysis further reinforced the significance of these genes in regulating LA accumulation. Moreover, our investigation of seed fatty acid composition at different seed developmental stages unveiled the crucial roles of FAD2 and FAD6 in LA biosynthesis. These findings offer important insights into enhancing breeding programs for the improvement of quality traits and provide reference resource for further research on the natural properties of safflower.

The effects of BDNF rs6265 and FGF21 rs11665896 polymorphisms on alcohol use disorder-related impulsivity in Han Chinese adults.

Introduction: Patients with alcohol use disorder (AUD) often experience repeated withdrawal. Impulsivity is the most relevant factor influencing successful withdrawal. Brain-derived neurotrophic factor (BNDF) and fibroblast growth factor 21 (FGF21) are associated with impulsivity. Previous studies on the differential effects of BDNF or FGF21 on impulsivity have focused on single-gene effects and have inconsistent results. We aim to investigate the effects of BDNF rs6265 and FGF21 rs11665896, individually and together, on impulsivity during alcohol withdrawal in patients with AUD. Methods: We recruited 482 adult Han Chinese males with AUD and assessed their impulsivity using the Barratt Impulsivity Scale. Genomic DNA was extracted and genotyped from peripheral blood samples. Statistical analysis was conducted on the data. Results: The T-test and 2 × 2 analysis of variance were used to investigate the effects of the genes on impulsivity. There was a significant BDNF × FGF21 interaction on no-planning impulsiveness (F = 9.15, p = 0.003, η2p = 0.03). Simple main effects analyses and planned comparisons showed that BDNF rs6265 A allele × FGF21 rs11665896 T allele was associated with higher no-planning impulsiveness. Finally, hierarchical regression analyses revealed that only the interaction of BDNF and FGF21 accounted for a significant portion of the variance in no-planning impulsiveness. Conclusion and significance: The combination of BDNF rs6265 A allele and FGF21 rs11665896 T allele may increase impulsivity and discourage alcohol withdrawal. Our study provides a possible genetic explanation for the effects of associated impulsivity in patients with AUD from the perspective of gene-gene interactions.

Natural Product-Derived Phytochemicals for Influenza A Virus (H1N1) Prevention and Treatment.

Influenza A (H1N1) viruses are prone to antigenic mutations and are more variable than other influenza viruses. Therefore, they have caused continuous harm to human public health since the pandemic in 2009 and in recent times. Influenza A (H1N1) can be prevented and treated in various ways, such as direct inhibition of the virus and regulation of human immunity. Among antiviral drugs, the use of natural products in treating influenza has a long history, and natural medicine has been widely considered the focus of development programs for new, safe anti-influenza drugs. In this paper, we focus on influenza A (H1N1) and summarize the natural product-derived phytochemicals for influenza A virus (H1N1) prevention and treatment, including marine natural products, flavonoids, alkaloids, terpenoids and their derivatives, phenols and their derivatives, polysaccharides, and derivatives of natural products for prevention and treatment of influenza A (H1N1) virus. We further discuss the toxicity and antiviral mechanism against influenza A (H1N1) as well as the druggability of natural products. We hope that this review will facilitate the study of the role of natural products against influenza A (H1N1) activity and provide a promising alternative for further anti-influenza A drug development.

Potassium deficiency enhances imbalances in rice water relations under water deficit by decreasing leaf hydraulic conductance.

Potassium (K+) is an essential macronutrient for appropriate plant development and physiology. However, little is known about the mechanisms involved in the regulation of leaf water relations by K under water deficit. A pot experiment with two K supplies of 0.45 and 0 g K2O per pot (3 kg soil per pot) and two watering conditions (well-watered and water-deficit) was conducted to explore the effects of K deficiency on canopy transpiration characteristics, leaf water status, photosynthesis, and hydraulic traits in two rice genotypes with contrasting resistance to drought. The results showed that K deficiency reduced canopy transpiration rate by decreasing stomatal conductance, which led to higher canopy temperatures, resulting in limited water deficit tolerance in rice. In addition, K deficiency led to further substantial reductions in leaf relative water content and water potential under water deficit, which increased the imbalance in leaf water relations under water deficit. Notably, K deficiency limited leaf gas exchange by reducing leaf hydraulic conductance, but decreased the intrinsic water use efficiency under water deficit, especially for the drought-resistant cultivar. Further analysis of the underlying process of leaf hydraulic resistance revealed that the key limiting factor of leaf hydraulic conductance under K deficiency was the outside-xylem hydraulic conductance rather than the xylem hydraulic conductance. Overall, our results provide a comprehensive perspective for assessing leaf water relations under K deficiency, water deficit, and their combined stresses, which will be useful for optimal rice fertilization strategies.