Novel Pyrazole-4-Carboxamide Derivatives Containing Oxime Ether Group as Potential SDHIs to Control Rhizoctonia solani.

In the search for novel succinate dehydrogenase inhibitor (SDHI) fungicides to control Rhizoctonia solani, thirty-five novel pyrazole-4-carboxamides bearing either an oxime ether or an oxime ester group were designed and prepared based on the strategy of molecular hybridization, and their antifungal activities against five plant pathogenic fungi were also investigated. The results indicated that the majority of the compounds containing oxime ether demonstrated outstanding in vitro antifungal activity against R. solani, and some compounds also displayed pronounced antifungal activities against Sclerotinia sclerotiorum and Botrytis cinerea. Particularly, compound 5e exhibited the most promising antifungal activity against R. solani with an EC50 value of 0.039 µg/mL, which was about 20-fold better than that of boscalid (EC50 = 0.799 µg/mL) and 4-fold more potent than fluxapyroxad (EC50 = 0.131 µg/mL). Moreover, the results of the detached leaf assay showed that compound 5e could suppress the growth of R. solani in rice leaves with significant protective efficacies (86.8%) at 100 µg/mL, superior to boscalid (68.1%) and fluxapyroxad (80.6%), indicating promising application prospects. In addition, the succinate dehydrogenase (SDH) enzymatic inhibition assay revealed that compound 5e generated remarkable SDH inhibition (IC50 = 2.04 µM), which was obviously more potent than those of boscalid (IC50 = 7.92 µM) and fluxapyroxad (IC50 = 6.15 µM). Furthermore, SEM analysis showed that compound 5e caused a remarkable disruption to the characteristic structure and morphology of R. solani hyphae, resulting in significant damage. The molecular docking analysis demonstrated that compound 5e could fit into the identical binding pocket of SDH through hydrogen bond interactions as well as fluxapyroxad, indicating that they had a similar antifungal mechanism. The density functional theory and electrostatic potential calculations provided useful information regarding electron distribution and electron transfer, which contributed to understanding the structural features and antifungal mechanism of the lead compound. These findings suggested that compound 5e could be a promising candidate for SDHI fungicides to control R. solani, warranting further investigation.

Collective trauma: Childhood abuse, perceived discrimination, and COVID-19.

OBJECTIVE: Few studies have examined the interplay between collective trauma (e.g., the COVID-19 pandemic) and personal trauma (e.g., child abuse and discrimination). In a longitudinal child maltreatment study, with a community sample added, negative COVID impact (e.g., financial and mental health difficulties due to COVID) was examined in relation to childhood abuse exposure and perceived discrimination. METHOD: Adults (N = 135) completed an online survey about trauma- and pandemic-related experiences. Regressions examined predictors of negative COVID impact and posttraumatic stress disorder (PTSD) symptoms during the pandemic. RESULTS: Although cumulative maltreatment contributed to negative COVID impact, when high levels of cumulative maltreatment had been experienced in childhood, greater negative COVID impact did not significantly relate to PTSD symptoms: For these participants, PTSD symptoms were relatively high (but not at ceiling) in adulthood overall. Negative COVID impact predicted PTSD symptoms only at low levels of cumulative child abuse. Perceived discrimination was associated with negative COVID impact and PTSD symptomatology. CONCLUSIONS: Cumulative childhood abuse at high levels likely set the stage for PTSD symptoms in adulthood, regardless of negative COVID impact. Individuals with lower levels of cumulative childhood abuse had fewer PTSD symptoms unless COVID had a stronger negative impact on their lives. Discrimination contributed to lower pandemic-related well-being. Insight is provided into special vulnerabilities associated with maltreatment backgrounds and discrimination at times of collective challenges. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Suppression and Memory for Childhood Traumatic Events: Trauma Symptoms and Non-Disclosure.

Self-reported lost memory of child sexual abuse (CSA) can be mistaken for "repressed memory." Based on our longitudinal studies of memory and disclosure in child maltreatment victims who are now adults, we discuss findings relevant to "repressed memory cases." We examined relations between self-report of temporarily lost memory of CSA (subjective forgetting) and memory accuracy for maltreatment-related experiences (objective memory). Across two studies involving separate samples, we find evidence for memory suppression rather than repression: (1) Most adults who claimed temporary lost memory of CSA reported memory suppression and clarified that they could have remembered the event if asked; (2) subjective forgetting was positively associated with accurate objective memory for maltreatment-related experiences. Subjective forgetting was also related to increased adult trauma symptoms and related to childhood non-disclosure of CSA. Moreover, trauma-related psychopathology mediated the relation between non-disclosure and subjective forgetting. Implications for psychological theory and repressed memory cases are discussed.

EM-2, a natural sesquiterpene lactone from Elephantopus mollis H.B.K., enhanced the sensitivity of breast cancer cells to epirubicin by blocking protective autophagy.

BACKGROUND: EM-2, a natural sesquiterpene lactone isolated from Elephantopus mollis H.B.K., showed a good anti-breast cancer effect when combined with epirubicin (EPI). However, its synergistic sensitization mechanism remains unclear. PURPOSE: This study aimed to determine the therapeutic effect and possible synergistic mechanism of EM-2 with EPI in vivo and in vitro and to provide an experimental basis for the treatment of human breast cancer. METHODS: Cell proliferation was measured with MTT and colony formation assays. Apoptosis and reactive oxygen species (ROS) levels were examined through flow cytometry, and the expression levels of proteins related to apoptosis, autophagy, endoplasmic reticulum stress, and DNA damage were detected through Western blot analysis. Moreover, the caspase inhibitor Z-VAD-FMK, autophagy inhibitors bafilomycin A1 and chloroquine, ER stress inhibitor 4-phenylbutyric acid, and ROS scavenger N-acetyl cysteine were applied to verify signaling pathways. Breast cancer cell lines were used to evaluate the antitumor functions of EM-2 and EPI in vitro and in vivo. RESULTS: We demonstrated that in MDA-MB-231 and SKBR3 cells, the IC50 of EPI combined with EM-2 (IC20) was 37.909 and 33.889 times lower than that of EPI alone, respectively. Further study verified that in EPI-resistant lines (MDA-MB-231/EPI), the IC50 of EPI combined with EM-2 (IC20) was 26.305 times lower than that of EPI alone. Mechanistically, EM-2 could reverse the protective effect of EPI against autophagy in SKBR3 and MDA-MB-231 cells. EM-2 and EPI could trigger ER stress. When EM-2 and EPI were used in combination, ER stress was continuously activated, and ER stress-mediated apoptosis was induced. Meanwhile, EM-2 combined with EPI promoted DNA damage then induced apoptosis. In vivo, the volume of breast cancer xenografts in the combination group was smaller than that in the control, EM-2, and EPI groups. Immunohistochemical experiments demonstrated that the combination of EM-2 and EPI could block autophagy and promote ER stress in vivo. CONCLUSION: EM-2 enhances the sensitivity of MDA-MB-231, SKBR3, and EPI-resistant cells to EPI.

Childhood Sexual Abuse: A Longitudinal Study of Disclosures and Denials.

In legal cases regarding child sexual abuse (CSA), children have various options, such as to disclose or deny maltreatment. When interviewed in adulthood, their accounts may be consistent with their childhood responses. Alternatively, denial in childhood could be followed in adulthood by disclosure ("deferred disclosure"), confirming previous suspicions. Or the adults could possibly recant. We conducted a longitudinal study of CSA disclosures and denials (N = 99; Time 1 [T1], 3- to 16-year-olds). T1 CSA disclosures and denials at a forensic unit were compared to the individuals' responses 20 years later (Time 2 [T2]. 22- to 37-years-old). We found that consistent disclosure was associated with being older at T1 and female. Deferred disclosure was significantly associated with greater T2 trauma-related symptoms. Corroboration and higher CSA severity predicted T2 recantation. Consistent denial was related to less severe CSA. Our findings add to knowledge about CSA disclosures, which affect legal pathways available to child victims.

Memory Accuracy After 20 Years for Interviews About Child Maltreatment.

When adults allege childhood victimization, their long-term memory comes under scrutiny. This scrutiny can extend to the adults' memory of childhood interviews. The concerns raise important theoretical and applied issues regarding memory for long-past discussions of child maltreatment and trauma. In this longitudinal study, 104 adults, who as children (ages 3-15 years) were interviewed in child maltreatment investigations (Time 1), were questioned 20 years later (Time 2) about the Time 1 interviews. Verbatim documentation from Time 1 permitted scoring of memory accuracy. A subset of the participants (36%) reported no memory for the Time 1 interviews. Of the 64% who remembered being interviewed at Time 1, those who had been adolescents at Time 1 remembered the forensic interview discussion about abuse incidents better than discussion about general psychological issues. Adult trauma symptoms were associated with more accurate memory for interview content that directly concerned abuse experiences but not for non-abuse-specific information. Findings indicate that the veracity of adults' long-term memory for clinical/forensic conversations about childhood maltreatment depends on age at interview, interview content, and traumatization factors. Implications are discussed.