NtMYB27 acts downstream of NtBES1 to modulate flavonoids accumulation in response to UV-B radiation in tobacco.

UV-B radiation can induce the accumulation of many secondary metabolites, including flavonoids, in plants to protect them from oxidative damage. BRI1-EMS-SUPPRESSOR1 (BES1) has been shown to mediate the biosynthesis of flavonoids in response to UV-B. However, the detailed mechanism by which it acts still needs to be further elucidated. Here, we revealed that UV-B significantly inhibited the transcription of multiple transcription factor genes in tobacco, including NtMYB27, which was subsequently shown to be a repressor of flavonoids synthesis in tobacco. We further demonstrated that NtBES1 directly binds to the E-box motifs present in the promoter of NtMYB27 to mediate its transcriptional repression upon UV-B exposure. The UV-B-repressed NtMYB27 could bind to the ACCT-containing element (ACE) in the promoters of Nt4CL and NtCHS and served as a modulator that promoted the biosynthesis of lignin and chlorogenic acid (CGA) but inhibited the accumulation of flavonoids in tobacco. The expression of NtMYB27 was also significantly repressed by heat stress, suggesting its putative roles in regulating heat-induced flavonoids accumulation. Taken together, our results revealed the role of NtBES1 and NtMYB27 in regulating the synthesis of flavonoids during the plant response to UV-B radiation in tobacco.

Comparative Transcriptome Analysis of Hepatopancreas Reveals Sexual Dimorphic Response to Methyl Farnesoate Injection in Litopenaeus vannamei.

Sexually dimorphic traits such as growth and body size are often found in various crustaceans. Methyl farnesoate (MF), the main active form of sesquiterpenoid hormone in crustaceans, plays vital roles in the regulation of their molting and reproduction. However, understanding on the sex differences in their hormonal regulation is limited. Here, we carried out a comprehensive investigation on sexual dimorphic responses to MF in the hepatopancreas of the most dominant aquacultural crustacean-the white-leg shrimp (Litopenaeus vannamei). Through comparative transcriptomic analysis of the main MF target tissue (hepatopancreas) from both female and male L. vannamei, two sets of sex-specific and four sets of sex-dose-specific differentially expressed transcripts (DETs) were identified after different doses of MF injection. Functional analysis of DETs showed that the male-specific DETs were mainly related to sugar and lipid metabolism, of which multiple chitinases were significantly up-regulated. In contrast, the female-specific DETs were mainly related to miRNA processing and immune responses. Further co-expression network analysis revealed 8 sex-specific response modules and 55 key regulatory transcripts, of which several key transcripts of genes related to energy metabolism and immune responses were identified, such as arginine kinase, tropomyosin, elongation of very long chain fatty acids protein 6, thioredoxin reductase, cysteine dioxygenase, lysosomal acid lipase, estradiol 17-beta-dehydrogenase 8, and sodium/potassium-transporting ATPase subunit alpha. Altogether, our study demonstrates the sex differences in the hormonal regulatory networks of L. vannamei, providing new insights into the molecular basis of MF regulatory mechanisms and sex dimorphism in prawn aquaculture.

Responsiveness to Selective Laser Trabeculoplasty in Open-Angle Glaucoma and Ocular Hypertension.

Importance: Selective laser trabeculoplasty (SLT) is becoming the recommended first choice in the treatment of open-angle glaucoma (OAG). However, whether repeat SLT can be recommended regardless of initial response remains controversial. Objective: To assess the potential of OAG and ocular hypertension (OHT) undergoing repeat laser to respond favorably to SLT, termed responsiveness to SLT. Design, Setting, and Participants: This post hoc analysis of the Laser in Glaucoma and Ocular Hypertension Trial in China (LiGHT China) was conducted from March 2015 to April 2023 in Zhongshan Ophthalmic Center. Of 1376 newly diagnosed OAG and OHT eyes of 771 adults in the original trial, 180 eyes of 105 participants were included in the present study, which underwent initial and repeat SLT as primary treatments. Exposures: Standard SLT was the primary treatment. Repeat SLT was the first choice of treatment escalation regardless of initial response. IOP reduction after SLT and the duration of effect were analyzed. The maximum reduction in IOP within 2 years after initial SLT and repeat SLT was used to identify potential nonresponsiveness. Main Outcomes and Measures: IOP reduction 2 months after SLT. Results: A total of 180 eyes from 105 Chinese participants (mean [SD] age, 45.6 [14.5] years; 58 [55.2%] male and 47 [44.8%] female) underwent repeat SLT. Initial SLT and repeat SLT were both associated with a reduction in IOP (mean, 4.5 mm Hg; 95% CI, 3.9 to 5.1; P < .001 and mean, 3.3 mm Hg; 95% CI, 2.7 to 3.8; P < .001, respectively). The mean (SD) IOP after repeat SLT was 15.8 (3.4) mm Hg, similar to 16.0 (4.0) mm Hg after initial SLT (difference, -0.4mm Hg; 95% CI, -1.0 to 0.3; P = .24). Duration of effect after repeat SLT was longer than after initial SLT (1043 days vs 419 days; hazard ratio, 0.38; 95% CI, 0.29 to 0.50; P < .001). IOP reduction after initial SLT was uncorrelated with that after repeat SLT, and 153 eyes (85.0%) responded favorably to SLT at least once. A subset of 27 eyes (15.0%) was identified as potentially nonresponsive and found distinctive with older age (mean [SD], 54.1 [12.5] years vs 44.2 [14.2] years; difference, 10.5 years; 95% CI, 2.9 to 18.1; P = .009), higher proportion of female participants (difference, 27.5%; 95% CI, 3.6 to 51.5; P = .03), and lower baseline IOP (difference, -3.2 mm Hg; 95% CI, -5.2 to -1.3; P = .001). Conclusions and Relevance: These post hoc analyses showed that most cases of OAG and OHT were highly responsive to SLT and support the consideration of repeat SLT regardless of initial response, while individuals who are nonresponsive to this treatment may have specific features.

PI3KR1 and AKT1 in largemouth bass (Micropterus salmoides): molecular cloning, characterization, and its involvement in the alleviation of hepatic glycogen deposition caused by insulin inclusion in vitro.

In this study, the full-length cDNA sequences of the phosphatidylinositol-3-kinase p85 alpha (PI3KR1) and serine/threonine kinase 1 (AKT1) genes in largemouth bass (Micropterus salmoides) were obtained using the rapid amplification of cDNA ends (RACE) method. Sequence analysis revealed that the cloned sequences of PI3KR1 and AKT1 are 4170 bp and 3672 bp in length, with open reading frames (ORFs) of 1389 bp and 1422 bp encoding 462 and 473 amino acids, respectively. Sequence alignment and evolutionary tree analysis indicated their close relationship to other teleosts, especially those with similar feeding habits. Tissue distribution demonstrated widespread distribution of both genes in various tissues, with the highest abundance in the liver. Further results found that the upregulation of the expression of p-PI3KR1, p-AKT1, p-FoxO1, and GLUT2 proteins by insulin, while suppressing the expression of the total FoxO1 protein, effectively triggers a significant activation of the PI3KR1-AKT1 insulin signaling pathway. Meanwhile, the mRNA levels of the key glycolytic genes, including glucokinase (gk), pyruvate kinase (pk), and phosphofructokinase liver type (pfkl), have been enhanced evidently. In contrast, the expression of gluconeogenic genes such as phosphoenolpyruvate carboxykinase (pepck), glucose-6-phosphatase catalytic subunit (g6pc), and fructose-1,6-bisphosphatase-1 (fbp1) has been notably down-regulated. In addition, insulin treatment promoted the phosphorylation of glycogen phosphorylase (PYGL) and the dephosphorylation of glycogen synthase (GS), and the glycogen content in the insulin-treated group was remarkably reduced compared to the control group. Overall, our study indicates that the activation of PI3KR1-AKT1 insulin signaling pathway represses the hepatic glycogen deposition via the regulation of glycolysis and gluconeogenesis, which provides some new insights into nutritional strategy to effectively regulate the glucose metabolism in carnivorous fish.

Dickeya fangzhongdai was prevalent and caused taro soft rot when coexisting with the Pectobacterium complex, with a preference for Araceae plants.

Bacterial soft rot caused by coinfection with Dickeya spp. and Pectobacterium spp. in hosts can cause successive changes in fields, and it is difficult to prevent the spread of and control the infection. Pectobacterium spp. are prevalent in the growing areas of tuberous crops, including taro and potato. Recently, Dickeya fangzhongdai has emerged as a virulent pathogen in taro. To determine the prevalence status of the causal agents and evaluate the potential spreading risks of D. fangzhongdai, screening and taxonomic classification were performed on phytopathogenic bacteria collected from different taro-growing areas in Guangdong Province, China, and biological and genomic characteristics were further compared among typical strains from all defined species. The causative agents were verified to be phytobacterial strains of D. fangzhongdai, Pectobacterium aroidearum and Pectobacterium colocasium. P. aroidearum and P. colocasium were found to form a complex preferring Araceae plants and show intensive genomic differentiation, indicating their ancestor had adapted to taro a long time prior. Compared with Pectobacterium spp., D. fangzhongdai was more virulent to taro corms under conditions of exogenous infection and more adaptable at elevated temperatures. D. fangzhongdai strains isolated from taro possessed genomic components of additional T4SSs, which were accompanied by additional copies of the hcp-vgrG genes of the T6SS, and these contributed to the expansion of their genomes. More gene clusters encoding secondary metabolites were found within the D. fangzhongdai strains than within the Pectobacterium complex; interestingly, distinct gene clusters encoding zeamine and arylpolyene were both most similar to those in D. solani that caused potato soft rot. These comparisons provided genomic evidences for that the newly emerging pathogen was potentially equipped to compete with other pathogens. Diagnostic qPCR verified that D. fangzhongdai was prevalent in most of the taro-growing areas and coexisted with the Pectobacterium complex, while the plants enriching D. fangzhongdai were frequently symptomatic at developing corms and adjacent pseudostems and caused severe symptoms. Thus, the emerging need for intensive monitoring on D. fangzhongdai to prevent it from spreading to other taro-growing areas and to other tuberous crops like potato; the adjustment of control strategies based on different pathopoiesis characteristics is recommended.

Tracking the hologenome dynamics in aquatic invertebrates by the holo-2bRAD approach.

The "hologenome" concept is an increasingly popular way of thinking about microbiome-host for marine organisms. However, it is challenging to track hologenome dynamics because of the large amount of material, with tracking itself usually resulting in damage or death of the research object. Here we show the simple and efficient holo-2bRAD approach for the tracking of hologenome dynamics in marine invertebrates (i.e., scallop and shrimp) from one holo-2bRAD library. The stable performance of our approach was shown with high genotyping accuracy of 99.91% and a high correlation of r > 0.99 for the species-level profiling of microorganisms. To explore the host-microbe association underlying mass mortality events of bivalve larvae, core microbial species changed with the stages were found, and two potentially associated host SNPs were identified. Overall, our research provides a powerful tool with various advantages (e.g., cost-effective, simple, and applicable for challenging samples) in genetic, ecological, and evolutionary studies.

Double-stranded RNA induces antiviral transcriptional response through the Dicer-2/Ampk/FoxO axis in an arthropod.

Invertebrates mainly rely on sequence-specific RNA interference (RNAi) to resist viral infections. Increasing studies show that double-stranded RNA (dsRNA) can induce sequence-independent protection and that Dicer-2, the key RNAi player that cleaves long dsRNA into small interfering RNA (siRNA), is necessary for this protection. However, how this protection occurs remains unknown. Herein, we report that it is caused by adenosine triphosphate (ATP)-hydrolysis accompanying the dsRNA-cleavage. Dicer-2 helicase domain is ATP-dependent; therefore, the cleavage consumes ATP. ATP depletion activates adenosine monophosphate-activated protein kinase (Ampk) and induces nuclear localization of Fork head box O (FoxO), a key transcriptional factor for dsRNA-induced genes. siRNAs that do not require processing cannot activate the transcriptional response. This study reveals a unique nonspecific antiviral mechanism other than the specific RNAi in shrimp. This mechanism is functionally similar to, but mechanistically different from, the dsRNA-activated antiviral response in vertebrates and suggests an interesting evolution of innate antiviral immunity.

NtWIN1 regulates the biosynthesis of scopoletin and chlorogenic acid by targeting NtF6'H1 and NtCCoAMT genes in Nicotiana tabacum.

Scopoletin and chlorogenic acid (CGA) are important polyphenols that regulate plant growth, development, and stress resistance. The ERF transcription factor WAX INDUCER1 (WIN1) promotes the biosynthesis of cutin, suberine, and wax. However, its full roles in regulating the accumulation of plant secondary metabolites still remain to be further clarified. In this study, NtWIN1 gene encoding a SHINE-type AP2/ERF transcription factor of the Va subgroup was identified from N. tabacum. NtWIN1 showed high expression levels in tobacco stems, sepals, and pistils. Overexpression (OE) and knock-out of NtWIN1 showed that it promoted the accumulation of total polyphenols and altered their composition. Compare to that of WT plants, the CGA contents significantly increased by 25%-50% in the leaves, flowers, and capsules of OE lines, while the scopoletin contents in the OE plants significantly decreased by 30%-67%. In contrast, the CGA contents in ntwin1 lines reduced by 23%-26%, and the scopoletin contents in ntwin1 increased by 38%-75% compare to that of WT plants. Chromatin immunoprecipitation and Dual-Luc transcription activation assays showed that NtWIN1 could bind to the promoters of NtF6'H1 and NtCCoAMT, thereby modulating their expression. The scopoletin content in ntwin1/ntf6'h1 double mutant was significantly lower than that in ntwin1 and WT plants, but showed no significant differences with that in ntf6'h1 mutant, further indicating that the inhibition of NtWIN1 on scopoletin accumulation depends on the activity of NtF6'H1. Our study illustrates the new roles of NtWIN1, and provides a possible target for regulating the synthesis of polyphenols in tobacco.

Psychological factors promote the habituation effect on social workers' posttraumatic stress disorder symptoms after repeated COVID-19 outbreaks.

OBJECTIVE: The present study investigates whether psychological factors influence the habituation or sensitization effect during repeated COVID-19 outbreaks. METHOD: A total of 838 social workers from districts affected by different waves of COVID-19 outbreaks (two waves, n = 387; one wave, n = 177; zero waves, n = 274) reported their posttraumatic stress disorder (PTSD) symptoms, psychological security, emotional regulation, resilience, spiritual health, and social support (December 2021). RESULTS: The rate of PTSD among social workers stands at 34% (cutoff point 38). Social workers developed a habituation response amid the ongoing pandemic, with individuals who encountered a higher number of COVID-19 outbreaks exhibiting fewer symptoms of PTSD (F = 3.04, p < .05, η² = 0.007). Social workers who experienced two outbreaks had significantly lower PTSD symptoms than those who did not experience any (p = .018, 95% CI [0.431, 4.635]). A bootstrapped multiple mediation analysis indicates that psychological security (indirect effect: ß = -0.590, 95% CI [-0.989, -0.192]) and emotional regulation (indirect effect: ß = -0.474, 95% CI [-0.899, -0.069]) completely mediate the association between outbreaks of COVID-19 and PTSD symptoms. CONCLUSIONS: The incidence of PTSD symptoms was high in social workers. Chinese social workers underwent a habituation effect after repeated outbreaks of COVID-19. Improving psychological security and emotional regulation can reduce PTSD symptoms due to the repeated outbreak of COVID-19 among the public. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Exploring waste separation using an extended theory of planned behavior: a comparison between adults and children.

This study applied an extended model of the theory of planed behavior (TPB) to compare the differences in waste separation behavior between children (ages 9 to 12, N = 339) and adults (ages 18 to 66, N = 379). We examined the relations among waste separation attitude, subjective norm, perceived behavioral control, knowledge, awareness, intention, and behavior. The results showed waste separation knowledge of children was less than that of adults. Structure equation model results also revealed robust differences between children and adults. For adults, TPB variables (attitude, subjective norm, and perceived behavioral control) and knowledge are significantly positively related to their waste separation intention. Meanwhile, perceived behavioral control and intention are positively related to adults' behavior. However, for children, only perceived behavioral control and awareness are positively related to intention, and perceived behavioral control is positively related to behavior. Moreover, the predictive power of the extended TPB model on children's waste separation intention and behavior are lower than those of adults. The different results may be due to children's immature cognitive abilities. This study enhanced the understanding of the different waste separation behavior determinants between children and adults. The findings are useful for developing tailored policies and promoting children's waste separation behavior.

AntDAS-GCMS: A New Comprehensive Data Analysis Platform for GC-MS-Based Untargeted Metabolomics with the Advantage of Addressing the Time Shift Problem.

Over the years, a number of state-of-the-art data analysis tools have been developed to provide a comprehensive analysis of data collected from gas chromatography-mass spectrometry (GC-MS). Unfortunately, the time shift problem remains unsolved in these tools. Here, we developed a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (AntDAS-GCMS) to perform total ion chromatogram peak detection, peak resolution, time shift correction, component registration, statistical analysis, and compound identification. Time shift correction was specifically optimized in this work. The information on mass spectra and elution profiles of compounds was used to search for inherent landmarks within analyzed samples to resolve the time shift problem across samples efficiently and accurately. The performance of our AntDAS-GCMS was comprehensively investigated by using four complex GC-MS data sets with various types of time shift problems. Meanwhile, AntDAS-GCMS was compared with advanced GC-MS data analysis tools and classic time shift correction methods. Results indicated that AntDAS-GCMS could achieve the best performance compared to the other methods.

Effects of chlorantraniliprole on the development, fecundity and prey consumption of a non-specific predator, Rhynocoris fuscipes (Hemiptera: Reduviidae).

Transplant treatment with chlorantraniliprole (CAP) is a proactive approach to protect transplanted plants from pests during early establishment and has been comprehensively applied in tobacco fields in Guangdong Province, China. However, it is not known whether the high dose of CAP in transplant treatments has lethal or sublethal effects on the generalist predator Rhynocoris fuscipes Fabricius (Hemiptera: Reduviidae). To address this concern, the mortalities of R. fuscipes were assessed when 2nd instar larvae of R. fuscipes were in direct contact with or consuming CAP and when their eggs were exposed to CAP. Furthermore, 2nd instar nymphs R. fuscipes were long-term exposed to CAP until they reached adulthood, and their life table parameters were determined. After exposure to CAP, the activity of detoxification enzymes (P450, CaeE and GST) and the functional respond of R. fuscipes to their preys Agrotis ipsilon larvae were determined. In this study, CAP at all concentrations did not significantly increase the mortality of 2nd instar of R. fuscipes nymphs in comparison with the control. The detoxification enzyme (P450, CarE and GST) activities and the number of A. ipsilon larvae consumed by R. fuscipes in the transplant treatment were not affected by CAP after 3-d or long-term exposure. These results indicated that CAP was harmless to R. fuscipes according to IOBC protocols. However, during the treatment of 2nd instar nymphs with a label rate of 15 g AI/ha and a 5× label rate of 75 g AI/ha, CAP significantly prolonged the pre-adult and pre-oviposition periods, and treated adults had lower oviposition. Attention should be given to the time interval between transplant treatment and the release of this biocontrol agent into the field to minimize the impact of CAP on the predator R. fuscipes.

Integrated analyses of ionomics, phytohormone profiles, transcriptomics, and metabolomics reveal a pivotal role of carbon-nano sol in promoting the growth of tobacco plants.

BACKGROUND: Carbon nano sol (CNS) can markedly affect the plant growth and development. However, few systematic analyses have been conducted on the underlying regulatory mechanisms in plants, including tobacco (Nicotiana tabacum L.). RESULTS: Integrated analyses of phenome, ionome, transcriptome, and metabolome were performed in this study to elucidate the physiological and molecular mechanisms underlying the CNS-promoting growth of tobacco plants. We found that 0.3% CNS, facilitating the shoot and root growth of tobacco plants, significantly increased shoot potassium concentrations. Antioxidant, metabolite, and phytohormone profiles showed that 0.3% CNS obviously reduced reactive oxygen species production and increased antioxidant enzyme activity and auxin accumulation. Comparative transcriptomics revealed that the GO and KEGG terms involving responses to oxidative stress, DNA binding, and photosynthesis were highly enriched in response to exogenous CNS application. Differential expression profiling showed that NtNPF7.3/NtNRT1.5, potentially involved in potassium/auxin transport, was significantly upregulated under the 0.3% CNS treatment. High-resolution metabolic fingerprints showed that 141 and 163 metabolites, some of which were proposed as growth regulators, were differentially accumulated in the roots and shoots under the 0.3% CNS treatment, respectively. CONCLUSIONS: Taken together, this study revealed the physiological and molecular mechanism underlying CNS-mediated growth promotion in tobacco plants, and these findings provide potential support for improving plant growth through the use of CNS.

Exogenous and Endogenous Dual-Activated Nanoladder for Precise Imaging of Mitochondrial Ferroptosis-Related Inhibition miRNA with Tumor Cell Specificity.

Developing precise tumor cell-specific mitochondrial ferroptosis-related inhibition miRNA imaging methods holds enormous potential for anticancer drug screening and cancer treatment. Nevertheless, traditional amplification methods still tolerated the limited tumor specificity because of the "off-tumor" signal leakage resulting from their "always-active" sensing mode. To overcome this limitation, we herein developed a dual (exogenous 808 nm NIR light and endogenous APE1) activated nanoladder for precise imaging of mitochondrial ferroptosis-related miRNA with tumor cell specificity and improved imaging resolution. Exogenous NIR light-activation can regulate the ferroptosis-related inhibition miRNA imaging signals within mitochondria, and endogenous enzyme-activation can confine signals to tumor cells. Based on this dual activation design, off-tumor signals were greatly reduced and tumor-to-background contrast was enhanced with an improved tumor/normal discrimination ratio, realizing tumor cell-specific precise imaging of mitochondrial ferroptosis-related inhibition miRNA.

Broiler Spaghetti Meat Abnormalities: Muscle Characteristics and Metabolomic Profiles.

Spaghetti meat (SM) is a newly identified muscle abnormality that significantly affects modern broiler chickens, consequently exerting a substantial economic impact on the poultry industry worldwide. However, investigations into the meat quality and the underlying causative factors of SM in broilers remain limited. Therefore, this study was undertaken to systematically evaluate meat quality and muscle fiber characteristics of SM-affected meat. To elucidate the disparities between SM-affected and normal (NO) muscles in broiler chickens reared under identical conditions, we selected 18 SM-affected breast tissues and 18 NO breast tissues from 200 broiler chickens raised according to commercial standards under the same conditions for our study. The results showed that compared with the NO group, the muscle surface of the SM group lost integrity, similar to strip and paste. The brightness and yellowness values were significantly higher than those of the NO group. On the contrary, the shear force and protein were significantly lower in the SM group. Microscopic examination revealed that the muscle fibers in the SM group were lysed, necrotic, and separated from each other, with a large number of neutrophils diffusely distributed on the sarcolemma and endometrium. Thirty-five significantly different metabolites were observed in the breast muscles between both groups. Among them, the top differential metabolites-14,15-DiHETrE, isotretinoin, L-malic acid, and acetylcysteine-were mainly enriched in lipid metabolism and inflammatory pathways, including linoleic acid, arachidonic acid, phenylalanine, and histidine metabolism. Overall, these findings not only offer new insights into the meat quality and fiber traits of SM but also contribute to the understanding of potential mechanisms and nutritional regulators for SM myopathy.

Genome-wide analysis and expression profiling of the HD-ZIP gene family in kiwifruit.

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

Targeting the Cdc2-like kinase 2 for overcoming platinum resistance in ovarian cancer.

Platinum resistance represents a major barrier to the survival of patients with ovarian cancer (OC). Cdc2-like kinase 2 (CLK2) is a major protein kinase associated with oncogenic phenotype and development in some solid tumors. However, the exact role and underlying mechanism of CLK2 in the progression of OC is currently unknown. Using microarray gene expression profiling and immunostaining on OC tissues, we found that CLK2 was upregulated in OC tissues and was associated with a short platinum-free interval in patients. Functional assays showed that CLK2 protected OC cells from platinum-induced apoptosis and allowed tumor xenografts to be more resistant to platinum. Mechanistically, CLK2 phosphorylated breast cancer gene 1 (BRCA1) at serine 1423 (Ser1423) to enhance DNA damage repair, resulting in platinum resistance in OC cells. Meanwhile, in OC cells treated with platinum, p38 stabilized CLK2 protein through phosphorylating at threonine 343 of CLK2. Consequently, the combination of CLK2 and poly ADP-ribose polymerase inhibitors achieved synergistic lethal effect to overcome platinum resistance in patient-derived xenografts, especially those with wild-type BRCA1. These findings provide evidence for a potential strategy to overcome platinum resistance in OC patients by targeting CLK2.

CIRCVMA21-RELATED PATHWAY ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED HK-2 CELL INJURY.

ABSTRACT: Background : It is reported that circVMA21 has an inhibition effect on sepsis-induced acute kidney injury (AKI). Therefore, the underlying molecular mechanisms of circVMA21 in AKI are worthy of further investigation. Material and Methods : Lipopolysaccharide (LPS) was used to induce HK2 cell injury. CircVMA21, miR-337-3p and ZEB2 expression was tested by qRT-PCR. Cell growth was detected by CCK8 assay, EdU assay, and flow cytometry. Protein levels were examined by western blot. The levels of inflammatory factors and oxidative stress markers were measured to evaluate cell inflammatory response and oxidative stress. RNA relationship as verified by dual-luciferase reporter assay, RIP assay, and RNA pull-down assay. Results : CircVMA21 had decreased expression in AKI patients. Overexpressed circVMA21 alleviated LPS-induced HK2 cell inflammation, apoptosis, and oxidative stress. Moreover, circVMA21 sponged miR-337-3p, and miR-337-3p targeted ZEB2. The inhibitory effect of circVMA21 on LPS-induced HK2 cell injury was reversed by miR-337-3p overexpression, and ZEB2 overexpression abolished the promotion effect of miR-337-3p on LPS-induced HK2 cell injury. Conclusions : CircVMA21 could inhibit LPS-induced HK2 cell injury via miR-337-3p/ZEB2 axis.

Design, synthesis, and evaluation of novel ferrostatin derivatives for the prevention of HG-induced VEC ferroptosis.

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

Correction: Ionic migration induced loss analysis of perovskite solar cells: a poling study.

Correction for 'Ionic migration induced loss analysis of perovskite solar cells: a poling study' by Xue Zheng et al., Phys. Chem. Chem. Phys., 2022, 24, 7805-7814, https://doi.org/10.1039/D1CP05450C.