Diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease.

The purpose of this study was to explore the diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease. In this study, we first collected 161 samples from the GEO database (including 87 in the AD group and 74 in the normal group). Subsequently, through differential expression analysis and the iUUCD 2.0 database, we obtained 3450 Differentially Expressed Genes (DEGs) and 806 Ubiquitin-related genes (UbRGs). After taking the intersection, we obtained 128 UbR-DEGs. Secondly, by conducting GO and KEGG enrichment analysis on these 128 UbR-DEGs, we identified the main molecular functions and biological pathways related to AD. Furthermore, through the utilization of GSEA analysis, we have gained insight into the enrichment of functions and pathways within both the AD and normal groups. Further, using lasso regression analysis and cross-validation techniques, we identified 22 characteristic genes associated with AD. Subsequently, we constructed a logistic regression model and optimized it, resulting in the identification of 6 RUbR-DEGs: KLHL21, WDR82, DTX3L, UBTD2, CISH, and ATXN3L. In addition, the ROC result showed that the diagnostic model we built has excellent accuracy and reliability in identifying AD patients. Finally, we constructed a lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) regulatory network for AD based on six RUbR-DEGs, further elucidating the interaction between UbRGs and lncRNA, miRNA. In conclusion, our findings will contribute to further understanding of the molecular pathogenesis of AD and provide a new perspective for AD risk prediction, early diagnosis and targeted therapy in the population.

Ovarian Microcystic Stromal Tumor with Significant Nestin Expression: A Unique Case.

Ovary microcystic stromal tumor (MCST) is an extremely rare subtype of sex cord-stromal neoplasm, and only 57 cases have been reported. We herein report a unique case of ovarian MCST with positive nestin expression in a 39-year-old Chinese woman. The tumor showed microcystic stromal histological structures and characteristically expressed the CD10, WT-1, and Ki67 proteins. A molecular analysis identified a point mutation (c.110C > T) in exon 3 of the CTNNB1 gene. To our knowledge, no report has described a case of ovarian MCST with positive staining for nestin protein. Our study provides new insights into the tumor biology of ovarian MCST.

A novel HDAC6 inhibitor attenuate APAP-induced liver injury by regulating MDH1-mediated oxidative stress.

Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.

Non-pharmacological therapies for the management of the cognitive dysfunctions in post-stroke patients: a systematic review and network meta-analysis.

OBJECTIVE: To investigate the comparative effects of non-pharmacological therapies for managing global, attention, memory and execution cognitive functions in stroke patients. DESIGN: We searched PubMed, EMBASE, CINAHL, Cochrane Library, Web of Science, PEDro and Google Scholar for randomized controlled trials (RCTs) that evaluated the effects of non-pharmacological therapies for treating stroke cognitive dysfunctions. We performed a network meta-analysis (NMA) to estimate the mean treatment effect of 95% credible interval (CrI). RESULTS: 73 RCTs were included in the NMA for evidence syntheses. All therapies had significant effects than control on global cognition in stroke patients. Combined therapy was superior to other therapies for global cognition of all patients (vs cognitive task therapy: 0.71, 95%CrI 0.14 to 1.29; vs exercise: 0.88, 95%CrI 0.31 to 1.45, vs physical modality therapy: 0.77, 95%CrI 0.16 to 1.40). Different therapies have effects on specific cognitive domains in stroke patients. CONCLUSIONS: Our findings suggest that non-pharmacological therapies are effective in improving global cognitive function in stroke patients, with cognitive task therapy, exercise therapy, physical modality therapy, and combined therapy being viable options (most optimal approach: combined therapy). Precise selection of therapies based on the time since stroke onset and specific cognitive domains can further enhance treatment outcomes.

Lagerstroemiastenophylla (Lythraceae), a new species from China.

Lagerstroemiastenophylla, a new species from southeastern Shaanxi Province and northwestern Hubei Province of China is described. Morphologically, L.stenophylla resembles L.subcostata, but it differs in having 4-angular, subalate branchlets, elliptic-lanceolate, or narrowly elliptic leaves, and relatively larger flowers.

[Clinical effect of acupuncture based on syndrome differentiation in the treatment of chronic insomnia and its influence on cognitive function].

OBJECTIVE: To compare the effect of acupuncture based on syndrome differentiation and estazolam in the treatment of chronic insomnia and its influence on cognitive function. METHODS: A total of 90 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 45 cases in each group. The acupuncture group was treated with acupuncture at Sishencong (EX-HN 1) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6) combined with compatibility of acupoints based on syndrome differentiation, once a day for 6 d and then rest for 1 d, for a total of 4 weeks. The medication group was treated with oral estazolam tablets before bedtime, 1 tablet each time, for a total of 4 weeks. Before and after treatment, the scores of Pittsburgh sleep quality index (PSQI), mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and auditory verbal memory test (AVMT) of the two groups were compared, and the effects were evaluated. RESULTS: After treatment, the PSQI sub-item scores and total scores of the two groups were lower than those before treatment ( P<0.05 ), and above scores in the acupuncture group were lower than those in the medication group ( P<0.05 ); the scores of MMSE, MoCA and AVMT in the two groups were higher than those before treatment ( P<0.05 ), and the scores in the acupuncture group were higher than those in the medication group ( P<0.05 ). The total effective rate of the acupuncture group was 80.0% (36/45), which was higher than 53.3% (24/45) in the medication group (P<0.05). CONCLUSION: Syndrome differentiation acupuncture can improve the sleep quality and cognitive function of patients with chronic insomnia, and the curative effect is better than that of estazolam.

Glucose metabolism profile recorded by flash glucose monitoring system in patients with hypopituitarism during prednisone replacement.

BACKGROUND: Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications. AIM: To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes. METHODS: Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet ß-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs. RESULTS: Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet ß-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-ß compared with that of NCs; a notable difference in HOMA-ß was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-ß, and fasting glucose/insulin ratio when compared with NCs. CONCLUSION: Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.

The use of fluorescence laparoscopy in the resection of splenic tissue replantation in the right lobe of the liver: A case report and literature review.

BACKGROUND: Ectopic replantation and regeneration of splenic tissue fragments following splenic trauma or splenectomy is known as replantation of splenic tissue. It typically takes place in the abdominal cavity, however, splenic tissue replantation in the liver is extremely rare and difficult to diagnose. It is often misdiagnosed as a liver tumor and removed. CASE PRESENTATION: We present the case of a patient with a history of traumatic splenectomy 15 years prior to the replantation of splenic tissue in the liver. A 4 cm mass in the liver was found during the most recent physical examination, and a computed tomography scan indicated the possibility of a malignant tumor. The tumor was then removed using fluorescence laparoscopy. CONCLUSION: There is a possibility of intrahepatic replantation of splenic tissue in patients who have had a splenectomy in the past, have recently discovered an intrahepatic space-occupying lesion, and do not have any high-risk factors for liver cancer. Unnecessary surgery can be avoided if 99mTc-labeled red blood cells imaging using mass puncture or radionuclide examination provides a clear preoperative diagnosis. Globally, there are no reports of the use of fluorescence laparoscopy in resecting replanted splenic tissue in the liver. Specifically, in the current case, there was no indocyanine green uptake in the mass, and only a small amount was found in the normally functioning liver tissue surrounding the tumor.

The Elk-3 target Abhd10 ameliorates hepatotoxic injury and fibrosis in alcoholic liver disease.

Alcoholic liver disease (ALD) and other forms of chronic hepatotoxic injury can lead to transforming growth factor ß1 (TGFß1)-induced hepatic fibrosis and compromised liver function, underscoring the need to develop novel treatments for these conditions. Herein, our analyses of liver tissue samples from severe alcoholic hepatitis (SAH) patients and two murine models of ALD reveals that the ALD phenotype was associated with upregulation of the transcription factor ETS domain-containing protein (ELK-3) and ELK-3 signaling activity coupled with downregulation of α/ß hydrolase domain containing 10 (ABHD10) and upregulation of deactivating S-palmitoylation of the antioxidant protein Peroxiredoxin 5 (PRDX5). In vitro, we further demonstrate that ELK-3 can directly bind to the ABHD10 promoter to inhibit its transactivation. TGFß1 and epidermal growth factor (EGF) signaling induce ABHD10 downregulation and PRDX5 S-palmitoylation via ELK-3. This ELK-3-mediated ABHD10 downregulation drives oxidative stress and disrupts mature hepatocyte function via enhancing S-palmitoylation of PRDX5's Cys100 residue. In vivo, ectopic Abhd10 overexpression ameliorates liver damage in ALD model mice. Overall, these data suggest that the therapeutic targeting of the ABHD10-PRDX5 axis may represent a viable approach to treating ALD and other forms of hepatotoxicity.

Blocking ATP-P1Rs axis attenuate alcohol-related liver fibrosis.

AIMS: The aim of this study was to explore the fibrogenic effects of ATP-P1Rs axis and ATP-P2Rs axis on alcohol-related liver fibrosis (ALF). MATERIALS AND METHODS: C57BL/6J CD73 knock out (KO) mice were used in our study. 8-12 weeks male mice were used as an ALF model in vivo. In conclusion, after one week of adaptive feeding, 5 % alcohol liquid diet was given for 8 weeks. High-concentration alcohol (31.5 %, 5 g/kg) was administered by gavage twice weekly, and 10 % CCl4 intraperitoneal injections (1 ml/kg) were administered twice weekly for the last two weeks. The mice in the control group were injected intraperitoneally with an equivalent volume of normal saline. Fasting for 9 h after the last injection, blood samples were collected, and related indicators were tested. In vitro, rat hepatic stellate cells (HSCs) were treated with 200 µM acetaldehyde to establish an alcoholic liver fibrosis for 48 h, then tested related indicators. KEY FINDINGS: We found that both adenosine receptors including adenosine A1, A2A, A2B, A3 receptors (A1R, A2AR, A2BR, A3R) and ATP receptors including P2X7, P2Y2 receptors (P2X7R, P2Y2R) were expressed increased in ALF. After CD73 was knocked out, we found that adenosine receptors expression decreased, ATP expression increased, and fibrosis degree decreased. SIGNIFICANCE: Based on the research, we discovered that adenosine plays a more important role in ALF. Therefore, blocking the ATP-P1Rs axis represented a potential treatment for ALF, and CD73 will become a potential therapeutic target.

Management of male erectile dysfunction: From the past to the future.

Erectile dysfunction is a common disease of the male reproductive system, which seriously affects the life quality of patients and their partners. At present, erectile dysfunction is considered as a social-psychological-physiological disease with complex etiology and various treatment methods. Oral PDE5I is the first-line treatment for erectile dysfunction with the advantages of high safety, good effect and non-invasiveness. But intracavernosal injection, hormonal replacement therapy, vacuum erection device, penile prosthesis implantation can also be alternative treatments for patients have organic erectile dysfunction or tolerance to PDE5I. With the rapid development of technologies, some new methods, such as low-intensity extracorporeal shock wave and stem cell injection therapy can even repair the organic damage of the corpora cavernosa. These are important directions for the treatment of male erectile dysfunction in the future. In this mini-review, we will introduce these therapies in detail.

Extremely Robust and Multifunctional Nanocomposite Fibers for Strain-Unperturbed Textile Electronics.

Textile electronics are needed that can achieve strain-unaltered performance when they undergo irregular and repeated strain deformation. Such strain-unaltered textile electronics require advanced fibers that simultaneously have high functionalities and extreme robustness as fabric materials. Current synthetic nanocomposite fibers based on inorganic matrix have remarkable functionalities but often suffer from low robustness and poor tolerance against crack formation. Here, we present a design for a high-performance multifunctional nanocomposite fiber that is mechanically and electrically robust, which was realized by crosslinking titanium carbide (MXene) nanosheets with a slide-ring polyrotaxane to form an internal mechanically-interlocked network. This inorganic matrix nanocomposite fiber featured distinct strain-hardening mechanical behavior and exceptional load-bearing capability (toughness approaching 60 MJ m-3 and ductility over 27%). It retained 100% of its ductility after cyclic strain loading. Moreover, the high electrical conductivity (>1.1 × 105 S m-1 ) and electrochemical performance (>360 F cm-3 ) of the nanocomposite fiber can be well retained after subjecting the fiber to extensive (>25% strain) and long-term repeated (10 000 cycles) dimensional changes. Such superior robustness allowed for the fabrication of the nanocomposite fibers into various robust wearable devices, such as textile-based electromechanical sensors with strain-unalterable sensing performance and fiber-shaped supercapacitors with invariant electrochemical performance for 10 000 strain loading cycles.

CD73 aggravates alcohol-related liver fibrosis by promoting autophagy mediated activation of hepatic stellate cells through AMPK/AKT/mTOR signaling pathway.

CD73 is a membrane-bound glycoprotein that can dephosphorylate AMP to adenosine. Increasing evidence has shown that CD73 is involved in the occurrence and development of liver fibrosis. However, the potential mechanism by which CD73 affects the progression of alcohol-related liver fibrosis (ALF) remains unknown. This study aimed to examine the role and mechanism of CD73 in autophagy in HSC-T6 cells and its role in ALF in mice that treated with alcohol plus CCl4. We found that CD73 knockout reduced serum alanine aminotransferase and aspartate aminotransferase levels and decreased liver injury and collagen deposition. Furthermore, autophagy-related indicators were downregulated in the liver fibrosis tissues of CD73-/- (EtOH + CCl4) mice. In vitro, the expression of CD73 and autophagy increased in activated HSC-T6 cells. Autophagy inhibitor, 3-methyladenine, reduced autophagy and activation of acetaldehyde-induced HSC-T6 cells. When using CD73-siRNA, autophagy in HSC-T6 cells was found to be downregulated. However, the CD73 plasmid increased the activation and autophagy of hepatic stellate cells (HSCs). In addition, CD73 induced autophagy through the AMPK/AKT/mTOR pathway, which is characterized by an increase in the ratio of P-AMPKα/AMPKα and a decrease in the ratio of P-AKT/AKT and P-mTOR/mTOR. Our study found that CD73 promotes HSCs activation by regulating autophagy through the AMPK/AKT/mTOR signaling pathway.

An Effective Inoculation Method for Phytophthora capsici on Black Pepper Plants.

Piper nigrum L. (black pepper) is a typical woody vine that is an economically important spice crop across the world. Black pepper production is significantly impacted by root rot disease caused by Phytophthora capsici, which has seriously influenced the industry development as a "choke point" problem. However, the molecular genetic mechanism of resistance in black pepper is unclear, leading to slow progress in the development of new black pepper varieties. An effective inoculation and precise sampling system for Phytophthora capsici on black pepper plants is essential for studying this plant-pathogen interaction. The main aim of this study is to demonstrate a detailed methodology where the basal head of black pepper is inoculated with Phytophthora capsici, while also providing a reference for the inoculation of woody vine plants. The basal head of the black pepper plant was pinpricked to damage it, and mycelial pellets covered the three holes to retain the moisture so the pathogen could infect the plant well. This method provides a better way of solving the instability that is caused by traditional inoculation methods including soil drench or root dipping. It also provides a promising means for studying the mode of action between plants and other soil-borne plant pathogens in agricultural precision breeding.

METTL3 m6A-dependently promotes miR-21-5p maturation to accelerate choriocarcinoma progression via the HIF1AN-induced inactivation of the HIF1A/VEGF pathway.

BACKGROUND: Gestational choriocarcinoma is a highly malignant neoplastic disease derived from pathological changes in trophoblastic cells. Recent evidences have shown that N6-methyladenosine (m6A) modifications play important role in modulating the development of multiple cancers, but the detailed mechanisms by which m6A-mediated choriocarcinoma progression have not been fully delineated. OBJECTIVES: This study aimed to investigate the role of m6A in choriocarcinoma and reveal its underlying molecular mechanisms. METHODS: The expression of METTL3, miR-21-5p and HIF1AN was detected using RT-qPCR in tissues and cells. The protein expression of METTL3, HIF1AN, HIF1A and VEGF were measured by western blot. The luciferase reporter assays and RNA immunoprecipitation (RIP) were used to verify the relationship between miR-21-5p and HIF1AN. The CCK-8, colony formation and transwell assays were used to detected cell proliferation and cell migration, respectively. RESULTS: Here, we demonstrated that the m6A methyltransferase-like 3 (METTL3) was aberrantly high-expressed in the clinical choriocarcinoma tissues and choriocarcinoma cell lines compared to the corresponding normal counterparts. The following functional experiments verified that silencing of METTL3 suppressed cell proliferation, migration, epithelial-mesenchymal transition (EMT) and tumorigenesis in vitro and in vivo to hamper the aggressiveness of choriocarcinoma. Next, the mechanical experiments confirmed that METTL3 promoted the maturation of miR-21-5p in an m6A-dependent manner, and elevated miR-21-5p subsequently degraded its downstream hypoxia-inducible factor asparagine hydroxylase (HIF1AN) by targeting its 3' untranslated regions (3'-UTR), resulting in the activation of the tumor-promoting HIF1A/VEGF pathway. Finally, the rescuing experiments verified that METTL3 ablation-induced inhibitory effects on the malignant phenotypes in choriocarcinoma were all abrogated by both miR-21-5p overexpression and HIF1AN downregulation. CONCLUSIONS: Collectively, this study firstly reported the involvement of the METTL3/m6A/miR-21-5p/HIF1AN signaling cascade in regulating the progression of choriocarcinoma, which provided novel biomarkers for the diagnosis and treatment of this disease.

Daphnoretin Arrests the Cell Cycle and Induces Apoptosis in Human Breast Cancer Cells.

Emerging evidence has shown that daphnoretin, one of the main active ingredients of Daphne giraldii Nitsche, processes antitumor activities in several tumor cells (e.g., colon cancer, lung cancer, cervical cancer, and osteosarcoma). However, the antitumor effect and its mechanism in breast cancer are unexplored. In this study, our data indicated that daphnoretin obviously suppressed the proliferation of breast cancer MCF-7 and MDA-MB-231 cells. Further studies showed that daphnoretin remarkably increased the p21 level, decreased cyclin E and CDK2 levels, and then arrested the cell cycle at the S phase. Moreover, daphnoretin obviously lowered the BCL-2 level and raised the levels of BAX and cleaved caspase-9 and -3, leading to cell apoptosis. Furthermore, daphnoretin remarkably decreased the ratio of p-PI3K/PI3K and p-AKT/AKT in breast cancer cells. Collectively, these findings demonstrated that daphnoretin could suppress breast cancer cell proliferation through cell cycle arrest and inducing apoptosis, which is related to the PI3K/AKT pathway.

Dietary Acid Load Was Positively Associated with the Risk of Hip Fracture in Elderly Adults.

Previous studies have shown that dietary acid load (DAL) harms bone health, but the evidence is inconsistent and insufficient. This study examined the relationships between DAL and the risk of hip fracture. This case−control study contained 1070 pairs of 1:1 age-, city-, and gender-matched incident cases and controls (mean age, 71 years) recruited in Guangdong, China. Dietary information was collected using a validated 79-item food frequency questionnaire through face-to-face interviews. DAL was estimated based on established algorithms for the potential renal acid load (PRAL) and net endogenous acid production (NEAP). Higher PRAL and NEAP were dose-dependently associated with a higher risk of hip fracture in both the conditional logistic regression model and restricted cubic spline analysis after adjusting for potential covariates. The multivariate-adjusted odds ratios and 95% CI of hip fracture for tertiles 2 and 3 (vs. 1) of DAL were 1.63 (1.18, 2.25) and 1.92 (1.36, 2.71) for PRAL and 1.81 (1.30, 2.53) and 2.55 (1.76, 3.71) for NEAP in all participants (all p-trends < 0.001), respectively. Subgroup analyses showed more pronounced associations in participants with a lower body mass index. Our findings suggested positive associations between the estimated DAL and the risk of hip fractures in the elderly Chinese population.

The complete chloroplast genome of Hydrocotyle pseudoconferta Masamune 1932 (Araliaceae).

Hydrocotyle pseudoconferta was an important medicinal plant. The complete plastid genome of this species was reported for the first time. The full length of the complete chloroplast genome is 153,302 bp, with a typical quadripartite organization: a large single-copy (LSC) region of 84,417 bp, a small single-copy (SSC) region of 18,767 bp, and a pair inverted repeat regions (IRa and IRb) with 25,059 bp for each. The complete chloroplast genome of H. pseudoconferta encoded 133 genes, comprising 86 protein-coding genes, 37 tRNA genes, 8 rRNA genes, and 2 pseudogenes. The phylogenetic analysis suggested the closest relationship between H. pseudoconferta and Hydrocotyle nepalensis.

Comparative Transcriptome and Metabolome Analysis of Resistant and Susceptible Piper Species Upon Infection by the Oomycete Phytophthora Capsici.

Phytophthora capsici is a destructive oomycete pathogen that causes devastating disease in black pepper, resulting in a significant decline in yield and economic losses. Piper nigrum (black pepper) is documented as susceptible to P. capsici, whereas its close relative Piper flaviflorum is known to be resistant. However, the molecular mechanism underlying the resistance of P. flaviflorum remains obscure. In this study, we conducted a comparative transcriptome and metabolome analysis between P. flaviflorum and P. nigrum upon P. capsici infection and found substantial differences in their gene expression profiles, with altered genes being significantly enriched in terms relating to plant-pathogen interaction, phytohormone signal transduction, and secondary metabolic pathways, including phenylpropanoid biosynthesis. Further metabolome analysis revealed the resistant P. flaviflorum to have a high background endogenous ABA reservoir and time-course-dependent accumulation of ABA and SA upon P. capsici inoculation, while the susceptible P. nigrum had a high background endogenous IAA reservoir and time-course-dependent accumulation of JA-Ile, the active form of JA. Investigation of the phenylpropanoid biosynthesis metabolome further indicated the resistant P. flaviflorum to have more accumulation of lignin precursors than the susceptible P. nigrum, resulting in a higher accumulation after inoculation. This study provides an overall characterization of biologically important pathways underlying the resistance of P. flaviflorum, which theoretically explains the advantage of using this species as rootstock for the management of oomycete pathogen in black pepper production.