Identifying Causal Genes for Thermo-Responsive Rosette Growth in Arabidopsis by Genome-Wide Association Study.

Temperature responsive plant growth, such as thermo-morphogenesis, varied greatly among Arabidopsis natural accessions. Here we describe a procedure to identify causal genes for thermo-morphogenesis variation by a genome-wide association study (GWAS). It includes methods of measuring thermo-responsive rosette growth architecture, using GWA-Portal webtool for GWAS, analyzing haplotypes, and validating functional natural variations. In addition, we discuss key factors that affect the success of identifying causal genes from GWAS.

Preparation of Antimony-Doped Tin Oxide Fly Ash Antistatic Composite and Its Properties in Filling EVA.

As a common coal-based solid waste, fly ash is widely used in material filling. However, due to the high resistivity of fly ash itself, the antistatic performance of the filling material is poor. Therefore, antistatic composite powder was prepared by coating nano-sized antimony-doped tin oxide (ATO) on the surface of fly ash, and its preparation mechanism was discussed. The composite powders were characterized by SEM, EDS, XRD and FTIR. The results show that the interaction between SiO2 and SnO2 appears at the wave number of 727.12 cm-1, and the obvious SnO2 crystal phase appears on the surface of fly ash. The volume resistivity of calcined fly ash is 1.72 × 1012 Ω·cm, and the volume resistivity of ATO fly ash is reduced to 6 × 103 Ω·cm. By analyzing the limiting oxygen index, melt index, tensile strength, elongation at break, cross-section morphology and surface electrical resistivity of EVA, it was found that the addition of antistatic powder to EVA can improve its antistatic performance without deteriorating the mechanical properties of EVA.

Sequential surgery for the treatment of type I knee ankylosis: a series of 62 cases.

BACKGROUNDS: The lack of systematic classification and standard treatment principles for knee ankylosis prevents optimal treatments. This study explored treatments for type I (mild) knee joint ankylosis. METHOD: This retrospective study analysed patients with knee joint ankylosis admitted from March 2013 to January 2018 who underwent sequential arthroscopic release. RESULT: The 62 patients had 12-36 (average, 18) months of follow-up. Thirty-eight patients were released; of these, 18 were assisted by limited incision with partial quadriceps femoris expansion myotomy and released according to arthroscopy. Six patients underwent lengthening and release of the quadriceps femoris. All surgeries combined with full-course rehabilitation resulted in improved joint mobility. The range of motion (ROM) of the knee joint recovered to a range of 0° to 85°-140° (mean: 118.32 ± 9.42°) from the preoperative range of 30°-70° (mean: 45° ± 15.50°). The clinical effect was evaluated according to the Judet criteria at the final follow-up. The outcomes at the last follow-up (at least for 1 year) were excellent in 55 cases, good in six cases, and fair in one case. CONCLUSION: Sequential arthroscopic release, minimal selective invasion of limited incision of partial quadriceps femoris expansion myotomy, assisted by pie-crusting technique to release, or quadriceps femoris lengthening, and release surgery for type I knee joint ankylosis, accompanied by early rehabilitation training provided satisfactory results without significant complications.

Efficacy and Safety of Pericapsular Nerve Group Block for Hip Fracture Surgery under Spinal Anesthesia: A Meta-Analysis.

Objective: To evaluate the effectiveness and safety of pericapsular nerve group (PENG) block for hip fracture surgery under spinal anesthesia. Methods: This meta-analysis was registered on INPLASY (INPLASY202270005). PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched to collect the randomized controlled trials of the PENG block applied to hip fracture surgery in the setting of spinal anesthesia, with the search period from inception to 1 May 2023. Two independent researchers gradually screened the literature, evaluated the quality, extracted the data, and eventually pooled data using RevMan 5.4. Results: Fifteen articles with 890 patients were enrolled. The combined results showed that the PENG block reduced pain scores during position placement (SMD = -0.35; 95% CI [-0.67, 0.02]; P=0.04; I2 = 0%). Subgroup analyses showed that compared to the unblocked group, the PENG block reduced pain scores at 12 h, 24 h, and 48 h postoperatively. The incidence of postoperative hypokinesia was reduced (RR = 0.11; 95% CI [0.01, 0.86]; P=0.04; I2 = 0.00%). The time to first walking was advanced (SMD = -0.90; 95% CI [-1.17, 0.63]; P < 0.00001; I2 = 0%). Conclusion: The PENG block can reduce postoperative pain and pain during spinal anesthesia positioning, which is helpful to improve the operability and comfort of spinal anesthesia and facilitate postoperative muscle strength recovery and early activity.

The Effect of Scalp Nerve Block on Postoperative Analgesia and Stress Response in Patients Undergoing Craniotomy: A Meta-Analysis.

Objective: To evaluate the effect of scalp nerve block (SNB) on postoperative analgesia and stress response in patients undergoing craniotomy by meta-analysis. Methods: PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials involving SNB for elective craniotomy under general anesthesia from inception to August 1, 2022. Meta-analysis was performed using RevMan 5.4 and Stata MP17.0. Based on scalp block operation time (preoperative block, postoperative block), different control groups (no block, normal saline), local anesthetic types (bupivacaine, levobupivacaine, ropivacaine), the postoperative pain score at different time points was analyzed by subgroup analysis. Results: 23 studies involving 1515 patients were included. The combined results showed that SNB could significantly reduce the pain scores at all time points compared with the control group (P < .05). Subgroup analysis showed that the analgesic effect of preoperative scalp nerve block was better than that of postoperative block, and the effect of ropivacaine and levobupivacaine was better than bupivacaine. SNB could reduce morphine consumption within 48 hours after surgery (SMD = -1.51, 95% CI -2.80 -0.21, P = .02, I2 = 89%). The first rescue analgesia time was significantly longer in the SNB group than the control group (SMD = 0.57, 95% CI 0.16-0.99, P = .01, I2 = 68.76%). Compared with the control group, the levels of postoperative angiotensin, intraoperative blood glucose, and both intraoperative and postoperative cortisol levels were significantly decreased (P < .05). SNB can inhibit hemodynamic changes caused by surgical stimulation and effectively reduce the incidence of postoperative nausea and vomiting (RR = 0.71, 95% CI 0.51~0.97, P = .03). Conclusion: Scalp nerve block is an effective analgesic that reduces pain within 48 hours after craniotomy. It effectively inhibit the stress response caused by surgical stimulation, stabilize hemodynamics, and reduce the incidence of postoperative nausea and vomiting.

Analysis of Dopamine Receptor D2 Gene Polymorphism and Correlation with Dyslipidemia in the Chinese Population.

Objective: The study aimed to explore the genotype and allele distributions of dopamine D2-like receptor (DRD2) gene -141C and C957T polymorphisms in the Chinese Han population with dyslipidemia, as well as their association with serum lipid levels. Methods: One hundred fifty patients with dyslipidemia and 150 healthy people were recruited as the case and the control groups, respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol levels were detected. The target sequence of DRD2 polymorphisms was amplified by polymerase chain reaction and genotyped via Sanger sequencing. Results: In DRD2 gene C957T (rs6277), three genotypes of CC, CT, and TT were detected with the frequencies of 92.67%, 6.67%, 0.67% in dyslipidemia cases, and 83.33%, 14.67%, 2.00% in the controls, respectively. The CT genotype and T allele frequencies were significantly low in the case group relative to the control group. After adjusting to other clinical indicators, the CT genotype of C957T polymorphism (hazard ratio = 0.401, 95% confidence interval = 0.181-0.890, p < 0.05) was still related to a significantly reduced risk of dyslipidemia. The C957T CT genotype carriers had the lowest values of serum TC, TG, LDL, and the highest values of serum HDL-C. Conclusion: DRD2 gene C957T polymorphism was an independent influencing factor associated with the susceptibility to dyslipidemia, and the CT genotype was associated with decreased odds of susceptibility to dyslipidemia.

Genome-Wide Association Study Identifies Rice Panicle Blast-Resistant Gene Pb4 Encoding a Wall-Associated Kinase.

Rice blast is one of the most devastating diseases, causing a significant reduction in global rice production. Developing and utilizing resistant varieties has proven to be the most efficient and cost-effective approach to control blasts. However, due to environmental pressure and intense pathogenic selection, resistance has rapidly broken down, and more durable resistance genes are being discovered. In this paper, a novel wall-associated kinase (WAK) gene, Pb4, which confers resistance to rice blast, was identified through a genome-wide association study (GWAS) utilizing 249 rice accessions. Pb4 comprises an N-terminal signal peptide, extracellular GUB domain, EGF domain, EGF-Ca2+ domain, and intracellular Ser/Thr protein kinase domain. The extracellular domain (GUB domain, EGF domain, and EGF-Ca2+ domain) of Pb4 can interact with the extracellular domain of CEBiP. Additionally, its expression is induced by chitin and polygalacturonic acid. Furthermore, transgenic plants overexpressing Pb4 enhance resistance to rice blast. In summary, this study identified a novel rice blast-resistant gene, Pb4, and provides a theoretical basis for understanding the role of WAKs in mediating rice resistance against rice blast disease.

Comparative evaluation of antitumor effects of TNF superfamily costimulatory ligands delivered by mesenchymal stem cells.

Stimulation of costimulatory receptors serves as an alternative immunotherapeutic strategy other than checkpoint inhibition. However, systemic administration of the agonistic antibodies is associated with severe toxicities, which is one of the major obstacles for their clinical application. This study aimed to develop a mesenchymal stem cell (MSC)-based system for tumor-targeted delivery of TNF superfamily ligands and assess their potential in enhancing antitumor immunity. Here we established an MSC-based system for tumor-targeted delivery of TNF superfamily ligands, including TNFSF4, 9 and 18. The TNFSF receptors (TNFRSFs) were evaluated in mouse models and patient samples for lung and colorectal cancers. TNFRSFs were all expressed at various levels on tumor-infiltrated lymphocytes, with TNFRSF18 being the most prevalent receptor. Human umbilical cord-derived MSCs expressing these costimulatory ligands (MSC-TNFSFs) effectively activated lymphocytes in vitro and elicited antitumor immunity in mice. TNFSF4 showed the least antitumor efficacy in both LLC1 and CT26 tumor models. MSC-TNFSF9 showed the most potent tumor-inhibiting effect in the LLC1 tumor model, while MSCs expressing TNFSF18 in combination with CXCL9 most significantly repressed CT26 tumor growth. Overall, TNFSF9 and TNFSF18 exhibited stronger lymphocyte-stimulating and antitumor activities than TNFSF4. Our study provides evidence that antitumor effects of agonism of different costimulatory receptors may vary in different tumor types and presents a promising approach for targeted delivery of TNF superfamily costimulatory ligands to avoid the systemic toxicities and side effects associated with immune agonist antibodies.

Analysis of Subclinical Thyroid Dysfunction and Metabolic Abnormality in 28568 Healthy People.

We analyzed the detection rates of metabolic syndrome (MetS) and subclinical thyroid dysfunction, including subclinical hyperthyroidism (SCHyper) and subclinical hypothyroidism (SCH), in healthy people, as well as their relationship. Clinical data were collected from 28,568 healthy individuals who underwent physical examinations. The detection rates of SCHyper, SCH, and MetS, as well as in different genders and ages, were analyzed. The detection rate of SCHyper and SCH in females was significantly higher than that in males (P < 0.001), but that of MetS in males was significantly higher than that in females (P < 0.001). In each age group, the detection rate of SCH in females was higher than that in males (P < 0.001). The detection rate of SCH was significantly different in different age groups (P < 0.001). The detection rates of hyperlipidemia (P < 0.001), obesity (P = 0.004), hypertension (P = 0.009), and hyperglycemia (P < 0.001) in the female SCH group were significantly higher than those in the normal group. The detection rates of hyperlipidemia (P = 0.006), obesity (P = 0.04), and hypertension (P = 0.04) in the male SCH group were higher than those in the normal group. The males with SCHyper were more prone to hyperlipidemia (P = 0.02) and obesity (P = 0.03). In addition, the female SCHyper group was not significantly different from the normal group (P > 0.05). Conclusively, the detection rate of SCHyper and SCH in females is higher than that in males, which increases with age. Attention should be paid to subclinical thyroid dysfunction in elderly people, especially females. Early individualized screening and early intervention should be carried out for people with abnormal metabolism.

5-Methoxytryptophan ameliorates endotoxin-induced acute lung injury in vivo and in vitro by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway.

BACKGROUND AND AIM: Endotoxin-induced acute lung injury (ALI) is a complicated and fatal condition with no specific or efficient clinical treatments. 5-Methoxytryptophan (5-MTP), an endogenous metabolite of tryptophan, was revealed to block systemic inflammation. However, the specific mechanism by which 5-MTP affects ALI still needs to be clarified. The purpose of this study was to determine whether 5-MTP protected the lung by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway. METHODS AND RESULTS: We used lipopolysaccharide (LPS)-stimulated C57BL/6 J mice and MH-S alveolar macrophages to create models of ALI, and 5-MTP (100 mg/kg) administration attenuated pathological lung damage in LPS-exposed mice, which was associated with decreased inflammatory cytokines and oxidative stress levels, upregulated protein expression of Nrf2 and HO-1, and suppressed Caspase-1 activation and NLRP3-mediated pyroptosis protein levels. Moreover, Nrf2-deficient mice or MH-S cells were treated with 5-MTP to further confirm the protective effect of the Nrf2/HO-1 pathway on lung damage. We found that Nrf2 deficiency partially eliminated the beneficial effect of 5-MTP on reducing oxidative stress levels and inflammatory responses and abrogating the inhibition of NLRP3-mediated pyroptosis induced by LPS. CONCLUSION: These findings suggested that 5-MTP could effectively ameliorate ALI by inhibiting NLRP3-mediated pyroptosis via the Nrf2/HO-1 signaling pathway.

Inhibition of BMP4 alleviates diabetic retinal vascular dysfunction via the VEGF and smad1/5 signalling.

Objective:The aim of our study was to determine the molecular mechanism of BMP4 (bone morphogenetic protein 4) in DR (diabetic retinopathy).Methods: Human retinal endothelial cell (HRECs) induced by high glucose to simulate one of the pathogenesis in the diabetic retinopathy (DR) model. RT-qPCR and western blot were used to detect the mRNA and protein levels of BMP4 in the STZ/HG group. Flow cytometry and TUNEL staining were performed to detect the apoptosis. Angiogenesis was evaluated by tube formation assay. Transwell assay and wound healing assay were used to detect cell migration ability. H&E staining was used to evaluate the pathological changes.Results: BMP4 was significantly upregulated in the STZ/HG group. Sh-BMP4 significantly inhibited the migration and angiogenesis of RVECs induced by HG. In addition, both in vivo and in vitro experiments confirmed that sh-BMP4 could significantly promote RVECs apoptosis in the HG/STZ group. Western blot results showed that sh-BMP4 could down-regulate the expressions of p-smad1, p-smad5 and VEGF.Conclusions: Inhibition of BMP4 could alleviate the damage of diabetic retinopathy by regulating the p-smad1/5/VEGF signaling axis, inhibiting angiogenesis and promoting apoptosis.

The intracellular immune receptor like gene SNC1 is an enhancer of effector-triggered immunity in Arabidopsis.

Plants contain many nucleotide-binding leucine-rich repeat (NLR) proteins that are postulated to function as intracellular immune receptors but do not yet have an identified function during plant-pathogen interactions. SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1 (SNC1) is one such NLR protein of the Toll-interleukin 1 receptor (TIR) type, despite its well-characterized gain-of-function activity and its involvement in autoimmunity in Arabidopsis (Arabidopsis thaliana). Here, we investigated the role of SNC1 in natural plant-pathogen interactions and genetically tested the importance of the enzymatic activities of its TIR domain for its function. The SNC1 loss-of-function mutants were more susceptible to avirulent bacterial pathogen strains of Pseudomonas syringae containing specific effectors, especially under constant light growth condition. The mutants also had reduced defense gene expression induction and hypersensitive responses upon infection by avirulent pathogens under constant light growth condition. In addition, genetic and biochemical studies supported that the TIR enzymatic activity of SNC1 is required for its gain-of-function activity. In sum, our study uncovers the role of SNC1 as an amplifier of plant defense responses during natural plant-pathogen interactions and indicates its use of enzymatic activity and intermolecular interactions for triggering autoimmune responses.

Multiple chromatin-associated modules regulate expression of an intracellular immune receptor gene in Arabidopsis.

The expression of an intracellular immune receptor gene SNC1 (SUPPRESSOR OF npr1, CONSTITUTIVE 1) is regulated by multiple chromatin-associated proteins for tuning immunity and growth in Arabidopsis. Whether and how these regulators coordinate to regulate SNC1 expression under varying environmental conditions is not clear. Here, we identified two activation and one repression regulatory modules based on genetic and molecular characterizations of five chromatin-associated regulators of SNC1. Modifier of snc1 (MOS1) constitutes the first module and is required for the interdependent functions of ARABIDOPSIS TRITHORAX-RELATED 7 (ATXR7) and HISTONE MONOUBIQUITINATION 1 (HUB1) to deposit H3K4me3 and H2Bub1 at the SNC1 locus. CHROMATIN REMODELING 5 (CHR5) constitutes a second module and works independently of ATXR7 and HUB1 in the MOS1 module. HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 15 (HOS15) constitutes a third module responsible for removing H3K9ac to repress SNC1 expression under nonpathogenic conditions. The upregulation of SNC1 resulting from removing the HOS15 repression module is partially dependent on the function of the CHR5 module and the MOS1 module. Together, this study reveals both the distinct and interdependent regulatory mechanisms at the chromatin level for SNC1 expression regulation and highlights the intricacy of regulatory mechanisms of NLR expression under different environment.

Recent advances in Chinese patent medicines entering the international market.

As an indispensable part of Traditional Chinese medicine (TCM), Chinese patent medicines have played an important role in preventing and treating diseases in China. Since they are easy to use, easy to store, and cost-effective, Chinese patent medicines have been generally accepted and widely used in Chinese clinical practice as a vital medical resource. In recent years, as TCM has developed and it has been accepted around the world, many Chinese patent medicine companies have gained international market access and successfully registered several Chinese patent medicines as over-the-counter (OTC) or prescription drugs in regions and countries that primarily use Western medicine such as the EU, Russia, Canada, Singapore, and Vietnam. Moreover, several Chinese patent medicines have been obtained the US Food and Drug Administration (FDA) approval conducting phase II or III clinical trials in the US. The current work has focused on several Chinese patent medicines that have been successfully registered or that have been submitted for registration abroad. Summarized here are recent advances in the efficacy and molecular mechanisms of these Chinese patent medicines to treat respiratory infectious diseases (Lianhua Qingwen capsules, Jinhua Qinggan granules, and Shufeng Jiedu Capsules), cardiovascular and cerebrovascular diseases (Compound Danshen Dripping Pills, Huatuo Zaizao pills, and Tongxinluo Capsules), cancers (a Kanglaite injection and a Shenqi Fuzheng Injection), and gynecological diseases (Guizhi Fuling Capsules). The hope is that this review will contribute to a better understanding of Chinese patent medicines by people around the world.

Genome-Wide Association Study Identifies a Rice Panicle Blast Resistance Gene Pb3 Encoding NLR Protein.

Rice blast is a worldwide fungal disease that seriously affects the yield and quality of rice. Identification of resistance genes against rice blast disease is one of the effective ways to control this disease. However, panicle blast resistance genes, which are useful in the fields, have rarely been studied due to the difficulty in phenotypic identification and the environmental influences. Here, panicle blast resistance-3 (Pb3) was identified by a genome-wide association study (GWAS) based on the panicle blast resistance phenotypes of 230 Rice Diversity Panel I (RDP-I) accessions with 700,000 single-nucleotide polymorphism (SNP) markers. A total of 16 panicle blast resistance loci (PBRLs) within three years including one repeated locus PBRL3 located in chromosome 11 were identified. In addition, 7 genes in PBRL3 were identified as candidate genes by haplotype analysis, which showed significant differences between resistant and susceptible varieties. Among them, one nucleotide-binding domain and Leucine-rich Repeat (NLR) gene Pb3 was highly conserved in multiple resistant rice cultivars, and its expression was significantly induced after rice blast inoculation. Evolutionary analysis showed that Pb3 was a typical disease resistance gene containing coiled-coil, NB-ARC, and LRR domains. T-DNA insertion mutants and CRISPR lines of Pb3 showed significantly reduced panicle blast resistance. These results indicate that Pb3 is a panicle blast resistance gene and GWAS is a rapid method for identifying panicle blast resistance in rice.

Predicting in-hospital mortality for MIMIC-III patients: A nomogram combined with SOFA score.

Predicting the mortality of patients provides a reference for doctors to judge their physical condition. This study aimed to construct a nomogram to improve the prediction accuracy of patients' mortality. Patients with severe diseases were screened from the Medical Information Mart for Intensive Care (MIMIC) III database; 70% of patients were randomly selected as the training set for the model establishment, while 30% were used as the test set. The least absolute shrinkage and selection operator (LASSO) regression method was used to filter variables and select predictors. A multivariable logistic regression fit was used to determine the association between in-hospital mortality and risk factors and to construct a nomogram. A total of 9276 patients were included. The area under the curve (AUC) for the clinical nomogram based on risk factors selected by LASSO and multivariable logistic regressions were 0.849 (95% confidence interval [CI]: 0.835-0.863) and 0.821 (95% CI: 0.795-0.846) in the training and test sets, respectively. Therefore, this nomogram might help predict the in-hospital mortality of patients admitted to the intensive care unit (ICU).

The Ameliorating Role of A Playful Situational Game Intervention in School-Aged Children Undergoing Ophthalmic Surgeries: A Randomized Controlled Trial.

PURPOSE: The objective of the study was to investigate if a playful situational game (PSG) intervention, as a perioperative procedure, could effectively alleviate stress and anxiety and improve postoperative outcomes for children to receive ophthalmic surgeries. METHODS: This trial enrolled 153 children, among which 116 met inclusion criteria and were randomized to control (n = 58, who did not participate in PSG) or PSG group (n = 58, who participated PSG). In the PSG group, children were arranged in renovated wards and allocated to play situational games specifically designed to improve surgery readiness. Satisfaction of the care from parents, posthospitalization behavioral change incidences, Yale Preoperative Anxiety Scale (YPAS) scores, induction compliance checklist (ICC) scores, and pediatric anesthesia emergence delirium (PAED) scores were documented as postoperative assessments. RESULTS: The PSG group demonstrated significantly higher satisfaction of the care from the parents (p = 0.004), and posthospitalization behavioral change incidences were markedly rarer in the PSG group (p = 0.015). The YPAS scores of the PSG group showed a slower increase compared to the control group before and after surgery (p < 0.001). ICC and PAED scores were also lower in the PSG group (p < 0.01). CONCLUSION: Our data could support that PSG is an effective intervention in alleviating the anxiety of children undergoing ophthalmic surgery and PSG can increase the satisfaction rate among patients and decrease behavioral change incidences. The adoption of PSG in children could potentially been promoted in the clinical setting.

A Simple Instrument for Intraoperative Fluoroscopic Localization of Anatomic Insertions in Medial Patellofemoral Ligament Reconstruction.

Medial patellofemoral ligament (MPFL) reconstruction is the most common operation for treating patellofemoral joint instability. Accurately identifying the fluoroscopic location of the MPFL anatomical insertion point is critical in this procedure. However, current radiographic localization has some limitations, such as inaccuracy and radiation exposure. We recommend a simpler and more accurate instrument for intraoperative fluoroscopic positioning.

AIG2A and AIG2B limit the activation of salicylic acid-regulated defenses by tryptophan-derived secondary metabolism in Arabidopsis.

Chemical defense systems involving tryptophan-derived secondary metabolites (TDSMs) and salicylic acid (SA) are induced by general nonself signals and pathogen signals, respectively, in Arabidopsis thaliana. Whether and how these chemical defense systems are connected and balanced is largely unknown. In this study, we identified the AVRRPT2-INDUCED GENE2A (AIG2A) and AIG2B genes as gatekeepers that prevent activation of SA defense systems by TDSMs. These genes also were identified as important contributors to natural variation in disease resistance among A. thaliana natural accessions. The loss of AIG2A and AIG2B function leads to upregulation of both SA and TDSM defense systems. Suppressor screens and genetic analysis revealed that a functional TDSM system is required for the upregulation of the SA pathway in the absence of AIG2A and AIG2B, but not vice versa. Furthermore, the AIG2A and AIG2B genes are co-induced with TDSM biosynthesis genes by general pathogen elicitors and nonself signals, thereby functioning as a feedback control of the TDSM defense system, as well as limiting activation of the SA defense system by TDSMs. Thus, this study uncovers an AIG2A- and AIG2B-mediated mechanism that fine-tunes and balances SA and TDSM chemical defense systems in response to nonpathogenic and pathogenic microbes.