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Summary Pumilio3 (Pum3), an evolutionarily distant homologue of the classical RNA-binding protein PUF (PUMILIO and FBF) family member, is also involved in the process of RNA metabolism through post-transcriptional regulation. However, the functions of Pum3 in mouse oocyte maturation and preimplantation embryonic development have not been elucidated. By comparing RNA levels in different tissues, we found that Pum3 was widely expressed in multiple tissues, but moderately predominant in the ovary. Histochemical staining suggested that the PUM3 protein exhibits positive signals in oocytes, granulosa cells and theca cells of different follicle stages. Oocyte immunofluorescence results showed a slightly higher level of PUM3 protein in metaphase II compared with the germinal vesicle (GV) stage. After knockdown of Pum3 in GV oocytes using siRNA injection (siPUM3), no obvious defect was observed in the processes of GV breakdown and polar body extrusion during in vitro maturation (IVM) for the siPum3 oocytes. Compared with the control group, the siPUM3 group displayed no significant abnormality in the cleavage and blastocyst formation rate of these fertilized oocytes. Therefore, we can conclude that depletion of Pum3 does not affect mouse oocyte maturation and early embryonic development in vitro.

The Yarlung Tsangpo-Brahmaputra River Basin (YBRB) has long been troubled by the competitive water development activities of India, China, and Bangladesh. While energy thirst and food security keep challenging the riparian States, climate-related changing monsoon pattern increases the potential for conflicts over scarce water. Based on a quantitative analysis of 400 water events spanning the years 1958–2020 of the basin, this research tries to provide a holistic understanding of the conflict and cooperation and explore the possibility of water war or ‘climate-based’ water war in the basin; and thus formulate more precise recommendations to help prevent and mitigate conflicts. The results of this quantitative research surprisingly reveal that, instead of being main causes of bilateral conflict in the basin, the ‘energy imperative’ and the ‘climate imperative’ have become two major catalysts for water cooperation in the basin, water war is therefore highly unlikely. However, current bilateral cooperation on climate change mainly involves ‘climate adaptation’; few efforts have yet been made cooperatively in the field of ‘climate mitigation’; while traditional disputes around food and energy persist, the imperative of ecological protection and the lack of attention to cooperative climate mitigation are set to intensify potential conflict in the YBRB.

Summary Background Paediatric obstructive sleep apnoea (OSA) is a sleep breathing disorder which may have dramatic effects on childhood behaviour, neurodevelopment, metabolism, and overall health in children. Malocclusion and craniofacial morphology may be related to paediatric OSA, and therefore provide information for clinicians to recognize, evaluate and treat patients with this sleeping disorder. Objective The aim of this systematic review was to summarize evidence regarding the association between paediatric OSA and children’s dental and craniofacial characteristics. Search methods PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to 1 June 2022. Selection criteria Cross-sectional studies, comparing dental or craniofacial characteristics using clinical dental examinations or radiographic findings between OSA children (less than 18 year, diagnosed with overnight polysomnography) and healthy children, were included. Data collection and analysis The Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies was used to assess the quality of included studies. RevMan software was used for performing the Meta-analyses. Results Sixteen studies were included. Meta-analyses showed that the overjet (MD = 0.86, 95% CI: 0.20 to 1.51; P = 0.01), the saggital skeletal jaw discrepancy (ANB; MD = 1.78, 95% CI: 1.04 to 2.52; P < 0.00001) and mandibular plane angle (FH-MP; MD = 3.65, 95% CI: 2.45 to 4.85; P < 0.00001) were greater in OSA-affected children. In contrast, the upper molar arch width (upper first deciduous molar width; MD = –1.86, 95% CI: –3.52 to –0.20; P = 0.03), (Upper second deciduous molar width; MD = –1.06, 95% CI: –1.88 to –0.24; P = 0.01), SNB (MD = –2.10, 95% CI: –3.11 to –1.09; P < 0.0001), and maxillary length (ANS-PNS; MD = –1.62, 95% CI: –2.66 to –0.58; P = 0.002) were smaller in the OSA group. Conclusions This review shows that OSA-affected children tend to present with mandibular retroposition or retrognathia, increased mandibular plane angle and excess anterior overjet. However, these findings need to be viewed with caution as the corresponding differences may not be significant clinically. Registration PROSPERO (CRD42020162274)

Wetlands, often called the “kidneys of the earth”, play an important role in maintaining ecological balance, conserving water resources, replenishing groundwater and controlling soil erosion. Wetland mapping is very challenging because of its complicated temporal dynamics and large spatial and spectral heterogeneity. An accurate global 30 m wetland dataset that can simultaneously cover inland and coastal zones is lacking. This study proposes a novel method for wetland mapping by combining an automatic sample extraction method, existing multi-sourced products, satellite time-series images and a stratified classification strategy. This approach allowed for the generation of the first global 30 m wetland map with a fine classification system (GWL_FCS30), including five inland wetland sub-categories (permanent water, swamp, marsh, flooded flat and saline) and three coastal tidal wetland sub-categories (mangrove, salt marsh and tidal flats), which was developed using Google Earth Engine platform. We first combined existing multi-sourced global wetland products, expert knowledge, training sample refinement rules and visual interpretation to generate large and geographically distributed wetland training samples. Second, we integrated the Landsat reflectance time-series products and Sentinel-1 synthetic aperture radar (SAR) imagery to generate various water-level and phenological information to capture the complicated temporal dynamics and spectral heterogeneity of wetlands. Third, we applied a stratified classification strategy and the local adaptive random forest classification models to produce the wetland dataset with a fine classification system at each 5∘×5∘geographical tile in 2020. Lastly, GWL_FCS30, mosaicked by 961 5∘×5∘ regional wetland maps, was validated using 25 708 validation samples, which achieved an overall accuracy of 86.44 % and a kappa coefficient of 0.822. The cross-comparisons with other global wetland products demonstrated that the GWL_FCS30 dataset performed better in capturing the spatial patterns of wetlands and had significant advantages over the diversity of wetland sub-categories. The statistical analysis showed that the global wetland area reached 6.38 million km2, including 6.03 million km2 of inland wetlands and 0.35 million km2 of coastal tidal wetlands, approximately 72.96 % of which were distributed poleward of 40∘ N. Therefore, we can conclude that the proposed method is suitable for large-area wetland mapping and that the GWL_FCS30 dataset is an accurate wetland mapping product that has the potential to provide vital support for wetland management. The GWL_FCS30 dataset in 2020 is freely available at https://doi.org/10.5281/zenodo.7340516 (Liu et al., 2022).

In this work, we systematically investigated the electrocatalytic activity of VC-Mo2C for N2 reduction to NH3 through DFT calculations.

By doping with Ca2+ or Ba2+, Eu2+ emitting centers will selectively occupy different Sr2+ sites, thus leading to the regulation of optical spectra of SCxMPO:Eu2+ and SByMPO:Eu2+, with emission colors gradually turning from yellow to orange (λex = 460 nm).

Lung cancer (LC) is a fatal malignancy and often accompanied with converting normal fibroblasts to cancer-associated fibroblasts (CAFs). Exosomal lncRNA AGAP2-AS1 has been elucidated to be a potent prognostic factor for LC, while its role in activating CAFs is largely unknown.We first extracted exosomes from LC patients and co-cultured them with MRC5 cells to observe the state of MRC5 cells, detect AGAP2-AS1 using real-time quantitative polymerase chain reaction, and then analyze the interaction between EIF4A3 and AGAP2-AS1 using RNA pull down experiments. CCK-8 assay was used to detect cell proliferation. Transwell experiments demonstrated the regulation of MRC5 cells and, finally, the role of MyD88/NF-κB in the downstream mechanism of EIF4A3/AGAP2-AS1 was explored by RNA interference technology and pyrrolidinedithiocarbamic acid inhibition.We demonstrated that exosomes from the LC patients (cancer-exo) notably increased the metastatic ability of MRC-5 cells, promoting the expressions of the CAF biomarkers and lncRNA AGAP2-AS1. Overexpression of lncRNA AGAP2-AS1 prominently activated MRC-5 cells. Moreover, EIF4A3 was upregulated in the cancer-exo-treated MRC-5 cells, and EIF4A3 was verified to bind with lncRNA AGAP2-AS1 to improve its stability. The MyD88/NF-κB signaling pathway was subsequently proved to be positively regulated by lncRNA AGAP2-AS1, and the promotive role of lncRNA AGAP2-AS1 in LC and activating CAFs was confirmed in vivo.The positive feedback of EIF4A3/AGAP2-AS1/MyD88/NF-κB signaling pathway contributed to the activation of CAFs and exacerbated LC in turn, revealing a novel regulatory axis underlying LC.

Nanogap antennas with strong electromagnetic fields of the "hot spot" in the gap region of two adjacent particles that can significantly improve the optical properties of fluorophores hold great potential for ultrasensitive bioanalysis. Herein, a DNA computation-mediated self-assembly of Au NBP dimer-based plasmonic nanogap antennas was designed for imaging of intracellular correlated dual disease biomarkers. It is worth noting that with the benefit from the electromagnetic fields of the "hot spot" in the gap region and strand displacement amplification, the fluorescence intensity can be enhanced ∼14.7-fold by Au NBP dimer-based plasmonic nanogap antennas. In addition, the AND-gate sensing mechanism was confirmed through monitoring the response of three designed nAP-PH1, m-PH1, and PH1 probes, the fluorescence recovery in different cell lines (Hela and L02), and inhibitor-treated cells, respectively. Furthermore, thanks to the "dual keys" activation design, such an "AND-gate" sensing manner can be used for ultrasensitive correlated multiplexed molecular imaging, demonstrating its feasible prospect in correlated multiplexed molecular imaging.

Depression is a serious psychological disorder with a rapidly increasing incidence in recent years. Clinically, selective serotonin reuptake inhibitors are the main therapy. These drugs, have serious adverse reactions, however. Traditional Chinese medicine has the characteristics of multiple components, targets, and pathways, which has huge potential advantages for the treatment of depression. The antidepressant potential of the herbal combination of Bupleurum chinense DC (Chaihu) and Paeonia lactiflora Pall (Baishao) has been extensively studied previously. In this review, we summarized the antidepressant active components and mechanism of Chaihu-Baishao herb pair. We found that it works mainly through relieving oxidative stress, regulating HPA axis, and protecting neurons. Nevertheless, current research of this combined preparation still faces many challenges. On one hand, most of the current studies only stay at the level of animal models, lacking of sufficient clinical double-blind controlled trials for further verification. In addition, studies on the synergistic effect between different targets and signaling pathways are scarce. On the other hand, this preparation has numerous defects such as poor stability, low solubility, and difficulty in crossing the blood-brain barrier.

In the case of acute myocardial infarction, after coronary angioplasty, thrombolytic therapy and cardiac arrest and rebound surgery, the ischemic myocardium of patients may suffer from blood reperfusion injury. However, this is an inevitable complication of treatment, mainly manifested in arrhythmia, myocardial stunning, heart failure and so on, and even death in severe cases. The main mechanisms of myocardial ischemia-reperfusion injury include inflammatory response, autophagy, apoptosis, oxidative stress response, calcium overload, mitochondrial dysfunction and so on. What makes me curious is the calcium overload mechanism, which is the main inducement of reperfusion injury, and can act with other inducing mechanisms to further aggravate reperfusion injury. It is an important cause of myocardial injury and provides a new idea for myocardial protection. This paper comprehensively discusses calcium overload from the perspective of the mechanism of ischemia-reperfusion injury.

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Carcinine is a natural imidazole-containing peptide derivative. It is widely used in the cosmetics industry as anti-aging supplement with antioxidant, anti-glycation and glycation reversal functions, and it also has a notable pharmacological effect as anti-tumor drug and in protection against retinopathy. However, a technological method for synthesis and production of carcinine has not been established. In this study, a whole-cell transformation system converting β-alanine and histamine to carcinine by the enzymes Ebony and phosphopantetheine transferase (Sfp) has been developed. The results revealed that the catalytic efficiency of the strain containing the fusion protein of Ebony and Sfp (Sfp-glycine-serine-glycine-Ebony, SGE) in Escherichia coli W3110 (WSGE strain) is significantly higher (7.45 mM) than the combinatorial strain of pET28a-ebony and pACYCDuet-sfp in E. coli BL21(DE3) (BSE strain) (2.17 mM). Under the optimal reaction conditions (25 ℃, pH 7.0, 12.5 g/L wet cells, 20 mM β-alanine and 40 mM histamine), the carcinine can be quickly synthesized within 24 h up to a concentration of 22.63 mM. To achieve a continuous and efficient conversion of the precursors, a batch-feeding catalysis was designed. With this system, β-alanine (40 mM) and histamine (40 mM) could be completely transformed to carcinine (40.34 mM) in 36 h with a productivity of 0.204 g/L h reaching a titer of 7.34 g/L. Hence, the batch-feeding whole-cell biocatalysis is a promising technology for the high yield production of carcinine which can promote the industrial production of carcinine.

G-protein-coupled receptors (GPCRs), also known as seven transmembrane receptors, are the largest family of cell surface receptors in eukaryotes. There are ∼800 GPCRs in human, regulating diverse physiological processes. The GPCRs are the most intensively studied drug targets. Drugs that target GPCRs account for about a quarter of the global market share of therapeutic drugs. Therefore, to develop physiologically relevant and robust assays to search new GPCR ligands or modulators remain the major focus of drug discovery research worldwide. Early functional GPCR assays mainly depend on the measurement of G-protein-mediated second messenger generation. Recent developments in GPCR biology indicate that the signaling of these receptors is much more complex than the oversimplified classical view. The GPCRs have been found to activate multiple G proteins simultaneously and induce β-arrestin-mediated signaling. They have also been found to interact with other cytosolic scaffolding proteins and form dimer or heteromer with GPCRs or other transmembrane proteins. Here, we mainly discuss technologies focused on detecting protein–protein interactions, such as fluorescence resonance energy transfer/bioluminescence resonance energy transfer (FRET/BRET), NanoLuc binary technology (NanoBiT), Tango, etc., and their applications in measuring GPCRs interacting with various signaling partners. In the final part, we also discuss the species differences in GPCRs when using animal models to study the in vivo functions of GPCR ligands, and possible ways to solve this problem with modern genetic tools.

At present, the load diagram of pumping wells mostly uses load sensors to obtain load data. However, the load sensor is prone to mechanical fatigue during the measurement process, which results in measurement data drift distortion and large errors. This paper presents an electrical parameter measurement method to improve this problem. The electrical indicator diagram is obtained by measuring the instantaneous input power of the driving motor of the pumping unit, calculating the transmission loss in real time, and establishing the mathematical model of the polished rod load and displacement of the pumping unit. The correctness and effectiveness of the electrical indicator diagram were verified by field experiments.

In recent years, ternary nickel-rich layered oxides have gradually replaced traditional binary cathode materials in the lithium-ion battery market due to their advantages of high energy density and environmental protection. However, their structural instability of cathode materials has seriously affected the cycle performance of the battery. In order to optimize the internal structure of LiNi0.5Co0.2Mn0.3O2, the first-principle calculation was carried out in advance. The energy band density, state density and volume changes were obtained by the simulation calculation. Meanwhile, the electrochemical performance of modified LiNi0.5Co0.2Mn0.3O2 prepared by in-situ doping Na and Cl by wet grinding solid phase method was investigated. The results show that the impedance, capacity and capacity retention data are very compatible with the simulation results. The modified sample exhibits a good cyclic stability with the capacity retention of 80.91% after 80 cycles at 1 C, which is higher than that of 70.00% for commercial LiNi0.5Co0.2Mn0.3O2. The scanning electron microscope characterization indicates that the co-doping of Na and Cl can effectively alleviate the corrosion of of LiNi0.5Co0.2Mn0.3O2 surface by electrolyte. Therefore, Na and Cl doping can effectively optimize the internal structure of LiNi0.5Co0.2Mn0.3O2 and improve its electrochemical performance. The combination of simulation calculation and experiment provides a new approach for the modification of ternary cathode materials.

Invasion of C. fulvum causes the most serious diseases affecting the reproduction of tomatoes. Cf-10-gene-carrying line showed remarkable resistance to Cladosporium fulvum. To exploit its defense response mechanism, we performed a multiple-omics profiling of Cf-10-gene-carrying line and a susceptible line without carrying any resistance genes at non-inoculation and 3 days post-inoculation (dpi) of C. fulvum. We detected 54 differentially expressed miRNAs (DE-miRNAs) between the non-inoculation and 3 dpi in the Cf-10-gene-carrying line, which potentially regulated plant-pathogen interaction pathways and hormone signaling pathways. We also revealed 3,016 differentially expressed genes (DEGs) between the non-inoculated and 3 dpi in the Cf-10-gene-carrying line whose functions enriched in pathways that were potentially regulated by the DE-miRNAs. Integrating DE-miRNAs, gene expression and plant-hormone metabolites indicated a regulation network where the downregulation of miRNAs at 3 dpi activated crucial resistance genes to trigger host hypersensitive cell death, improved hormone levels and upregulated the receptors/critical responsive transcription factors (TFs) of plant hormones, to shape immunity to the pathogen. Notably, our transcriptome, miRNA and hormone metabolites profiling and qPCR analysis suggested that that the downregulation of miR9472 potentially upregulated the expression of SAR Deficient 1 (SARD1), a key regulator for ICS1 (Isochorismate Synthase 1) induction and salicylic acid (SA) synthesis, to improve the level of SA in the Cf-10-gene-carrying line. Our results exploited potential regulatory network and new pathways underlying the resistance to C. fulvum in Cf-10-gene-carrying line, providing a more comprehensive genetic circuit and valuable gene targets for modulating resistance to the virus.

As an extension of single-valued neutrosophic sets, Single-valued neutrosophic fuzzy sets can deal with uncertain and inconsistent information at the same time. Considering this advantage, this paper proposes some aggregation operators based on single-valued neutrosophic fuzzy environment and combines VIKOR method to study the multi-attribute group decision making problem. Firstly, we define the generalized distance measure for single-valued neutrosophic fuzzy sets, and propose the weighted arithmetic averaging operator, weighted geometric averaging operator, generalized weighted averaging operator, and generalized weighted geometric operator of single-valued neutrosophic fuzzy sets. Secondly, the proposed operators are combined with the VIKOR method to construct a multi-attribute group decision making model. Finally, the model is applied to the green supplier selection problem, and the feasibility of the model is demonstrated by comparative analysis.

Anti-PD-1 therapy has shown promising outcomes in the treatment of different types of cancer. It is of fundamental interest to analyze the efficacy of anti-PD-1 therapy in cancer patients infected with hepatitis B virus (HBV) since the comorbidity of HBV and cancer is widely documented. We designed a multicenter retrospective study to evaluate the efficacy of anti-PD-1 therapy on non-liver cancer patients infected with HBV. We found anti-PD-1 therapy achieved much better outcomes in HBV+ non-liver cancer patients than their HBV– counterparts. We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from esophageal squamous cell carcinoma (ESCC) patients. We found both cytotoxicity score of T cells and MHC score of B cells significantly increased after anti-PD-1 therapy in HBV+ ESCC patients. We also identified CX3CR1high TEFF, a subset of CD8+ TEFF, associated with better clinical outcome in HBV+ ESCC patients. Lastly, we found CD8+ TEFF from HBV+ ESCC patients showing higher fraction of Exhaustionhi T than their HBV– counterpart. In summary, anti-PD-1 therapy on HBV+ non-liver cancer patients is safe and achieves better outcomes than that on HBV– non-liver cancer patients, potentially because HBV+ patients had higher fraction of Exhaustionhi T, which made them more efficiently respond to anti-PD-1 therapy.

Background: Gastrointestinal (GI) tumors are among the most prevalent malignant tumors worldwide. Recurrence and metastasis remain the leading causes of advanced GI tumor-related mortality. We present two rare cases of uterine cervical metastases from GI tumors and describe the clinical and pathological diagnosis, therapeutic options, and prognosis from a molecular biology perspective. Case presentation: We present the case of a 55-year-old Asian woman treated for sigmoid adenocarcinoma. The patient underwent a sigmoid colon resection without chemotherapy. Six months later, the tumor in the patient’s pelvis recurred, and she underwent pelvic lesion resection and bilateral adnexectomy. The patient underwent frequent chemotherapy, radiotherapy, targeted therapy, and immunotherapy after surgery. Five years later, the patient was diagnosed with intestinal cancer and cervical metastasis due to vaginal bleeding. Another case involved a 54-year-old Asian woman with poorly differentiated adenocarcinoma of the stomach who underwent radical gastrectomy, left adnexal metastasis 1 year later, and bilateral adnexectomy. After surgery, insufficient chemotherapy was administered, and a year later, vaginal bleeding revealed metastatic adenocarcinoma of the cervix. Conclusions: Although cervical metastases from gastrointestinal tumors are rare, physicians should be aware of this risk. According to these guidelines, surgical resection is necessary for isolated cervical metastases, and systemic treatment is preferred if multiple metastases are present. However, in the present case, surgery was performed despite multiple metastases, which prolonged the patient's survival and improved the quality of life. Treatment options should be individualized. It has been suggested that such patients undergo genetic testing to facilitate targeted drug selection and improve treatment outcomes.

Seven groups of different layering angles of Graphene oxide/Carbon fiber (GO-CF) hybrid reinforced shape memory composites are prepared by vacuum infiltration hot pressing system. The layering angles are respectively [0°]4, [±15°]s, [±30°]s, [±45°]s, [±60°]s, [±75°]s, and [90°]4. The shape fixation ratio, shape recovery ratio, and shape recovery driving force of GO-CF hybrid reinforced shape memory composites are investigated. The composite with the layering angle of [0°]4 has the minimum shape fixation ratio of 90.9%, the maximum shape recovery ratio of 97.6%, and the maximum recovery force of 2.83 N. Compared to [0°]4, the composite with the layering angle of [90°]4 has the 9.13% higher shape fixation ratio, but it has 16.1% lower shape recovery ratio and 59.4% lower recovery force. The microstructure of the composites is characterized and the microstructure of seven groups of composites is satisfactory. Therefore, the matrix within each group of composites has a similar effect on the shape memory properties of the composites. With the layering angle increased, the fiber resilience in the axial direction (X-direction) and the accumulated internal stress gradually decrease. With the layering angle increased, the shape fixation ratio and recovery time of GO-CF hybrid reinforced shape memory composites increase, while the shape recovery ratio, recovery force, and recovery rate decrease.

Testis size determination is an important question of reproductive biology. Sertoli cells are known to be a key determinant of mammalian testis size but the underlying molecular mechanisms remain incompletely understood. Previously we showed that highly conserved germ cell RNA-binding proteins, PUMILIO1(PUM1) and PUMILIO2 (PUM2), control mouse organ and body size through translational regulation, but how different cell types of the organs contribute to their organ size regulation has not been established. Here, we report a somatic role of PUM in gonad size determination. PUM1 is highly expressed in the Sertoli cells of the developing testis from embryonic and postnatal mice as well as in germ cells. Removal of Sertoli cell, but not germ cell, Pum1 gene, led to reduced testis size without significantly affecting sperm number or fertility. Knockout of PUM1 target, Cdkn1b, rescued the phenotype of reduced testis size, supporting a key role of Sertoli cell PUM1 mediated Cdkn1b repression in the testis size control. Furthermore, removal of Pum2 or both Pum1 and Pum2 in the Sertoli cells also only affected the testis size, not sperm development, with the biggest size reduction in Pum1/2 double knockout mice. We propose that PUM1 and PUM2 modulate the testis size through their synergistic translational regulation of cell cycle regulators in the Sertoli cell. Further investigation of the ovary or other organs could reveal if PUM-mediated translational control of cell proliferation of the supporting cell represents a general mechanism for organ size modulation.

The abscisic acid (ABA) receptor PYR/PYL/RCAR, located upstream of the ABA signaling pathway, recognizes ABA signals and initiates the primary process of signal transduction. In our previous study, we found that the PYL4 gene in tomato plants was significantly upregulated after exogenous treatment with the hormone ABA. The present study used virus-induced gene silencing (VIGS) to further elucidate the role of the PYL4 gene in response to drought in tomato (Solanum lycopersicum) plants. Under the drought treatment, the SlPYL4-silenced plants wilted faster than the control plants did. Physiological indicators showed that the total reactive oxygen species (ROS) content and superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities of the SlPYL4-silenced plants were lower than those of the control plants after 3 and 6 h of drought stress treatment. After 3 h of drought treatment, hydrogen peroxide (H2O2) and superoxide anion (O2−.) accumulated much more in the leaves of the SlPYL4-silenced plants than in the leaves of the control plants. These results indicated that PYL4 plays a positive role in drought tolerance in tomato plants. Our results also suggest that SlPYL4 is located upstream of the ABA pathway to regulate the expression of PP2C, SnRK, and AREB/ABF genes.