Regulation of endogenous hormone and miRNA in leaves of alfalfa (Medicago sativa L.) seedlings under drought stress by endogenous nitric oxide.

BACKGROUND: Alfalfa (Medicago sativa. L) is one of the best leguminous herbage in China and even in the world, with high nutritional and ecological value. However, one of the drawbacks of alfalfa is its sensitivity to dry conditions, which is a global agricultural problem. The objective of this study was to investigate the regulatory effects of endogenous nitric oxide (NO) on endogenous hormones and related miRNAs in alfalfa seedling leaves under drought stress. The effects of endogenous NO on endogenous hormones such as ABA, GA3, SA, and IAA in alfalfa leaves under drought stress were studied. In addition, high-throughput sequencing technology was used to identify drought-related miRNAs and endogenous NO-responsive miRNAs in alfalfa seedling leaves under drought stress. RESULT: By measuring the contents of four endogenous hormones in alfalfa leaves, it was found that endogenous NO could regulate plant growth and stress resistance by inducing the metabolism levels of IAA, ABA, GA3, and SA in alfalfa, especially ABA and SA in alfalfa. In addition, small RNA sequencing technology and bioinformatics methods were used to analyze endogenous NO-responsive miRNAs under drought stress. It was found that most miRNAs were enriched in biological pathways and molecular functions related to hormones (ABA, ETH, and JA), phenylpropane metabolism, and plant stress tolerance. CONCLUSION: In this study, the analysis of endogenous hormone signals and miRNAs in alfalfa leaves under PEG and PEG + cPTIO conditions provided an important basis for endogenous NO to improve the drought resistance of alfalfa at the physiological and molecular levels. It has important scientific value and practical significance for endogenous NO to improve plant drought resistance.

Mechanism of action of microRNA166 on nitric oxide in alfalfa (Medicago sativa L.) under drought stress.

BACKGROUND: Alfalfa is a perennial forage crop of high importance, but its cultivation is often affected by drought stress. Currently, the investigation of drought-related small RNAs is a popular research topic to uncover plant drought resistance mechanisms. Among these small RNAs, microRNA166 (miR166) is associated with drought in numerous plant species. Initial small RNA sequencing studies have shown that miR166 is highly responsive to exogenous nitric oxide (NO) and drought. Therefore, analyzing the expression of Msa-miR166 under nitric oxide and drought treatment is significant. RESULT: Bioinformatics analysis revealed that the miR166 family is widely distributed among plants, ranging from mosses to eudicots, with significant distribution differences between species. The evolutionary degree of Msa-miR166s is highly similar to that of Barrel medic (Medicago truncatula) and Soybean (Glycine max), but significantly different from the model plant Arabidopsis (Arabidopsis thaliana). It is suggested that there are no significant differences in miR166s within the species, and members of Msa-miR166s can form a typical stem-loop. The lowest level of exogenous nitric oxide was observed in Msa-miR166s under drought stress, followed by individual drought, and the highest level was observed after removing endogenous nitric oxide. CONCLUSION: In response to short-term drought, Msa-miR166s down-regulate expression in alfalfa (Medicago sativa L.). Exogenous nitric oxide can reduce the expression of Msa-miR166s in response to short-term drought. These findings suggest that Msa-miR166e-5p is responsive to environmental changes. The expression levels of target genes showed an opposite trend to Msa-miR166s, verifying the accuracy of Degradome sequencing in the early stage. This suggests that alfalfa experiences drought stress when regulated by exogenous nitric oxide, targeting HD ZIP-III, FRI, and CoA ligase genes. Additionally, the expression of Msa-miR166s in response to drought stress varies between leaves and roots, indicating spatiotemporal specificity.

Metabolomic Profiling and Drug Interaction Characterization Reveal Riboflavin As a Breast Cancer Resistance Protein-Specific Endogenous Biomarker That Demonstrates Prediction of Transporter Activity In Vivo.

Advancement of endogenous biomarkers for drug transporters as a tool for assessing drug-drug interactions (DDIs) depends on initial identification of biomarker candidates and relies heavily on biomarker validation and its response to reference inhibitors in vivo. To identify endogenous biomarkers of breast cancer resistance protein (BCRP), we applied metabolomic approaches to profile plasma from Bcrp-/-, multidrug resistance protein (Mdr)1a/1b-/-, and Bcrp/Mdr1a/1b-/- mice. Approximately 130 metabolites were significantly altered in Bcrp and P-glycoprotein (P-gp) knockout mice, indicating numerous metabolite-transporter interactions. We focused on BCRP-specific substrates and identified riboflavin, which was significantly elevated in the plasma of Bcrp single- and Bcrp/P-gp double- but not P-gp single-knockout mice. Dual BCRP/P-gp inhibitor elacridar caused a dose-dependent increase of the area under the plasma concentration-time curve (AUC) of riboflavin in mice (1.51- and 1.93-fold increases by 30 and 150 mg/kg elacridar, respectively). In three cynomolgus monkeys, we observed approximately 1.7-fold increases in the riboflavin concentrations caused by ML753286 (10 mg/kg), which correlated well with the increase of sulfasalazine, a known BCRP probe in monkeys. However, the BCRP inhibitor had no effect on isobutyryl carnitine, arginine, or 2-arachidonoyl glycerol levels. Additionally, clinical studies on healthy volunteers indicated low intrasubject and intermeal variability of plasma riboflavin concentrations. In vitro experiments using membrane vesicles demonstrated riboflavin as a select substrate of monkey and human BCRP over P-gp. Collectively, this proof-of-principle study indicates that riboflavin is a suitable endogenous probe for BCRP activity in mice and monkeys and that future investigation of riboflavin as a blood-based biomarker of human BCRP is warranted. SIGNIFICANCE STATEMENT: Our results identified riboflavin as an endogenous biomarker candidate of BCRP. Its selectivity, sensitivity, and predictivity regarding BCRP inhibition have been explored. The findings of this study highlight riboflavin as an informative BCRP plasma biomarker in animal models. The utility of this biomarker requires further validation by evaluating the effects of BCRP inhibitors of different potencies on riboflavin plasma concentrations in humans. Ultimately, riboflavin may shed light on the risk assessment of BCRP DDIs in early clinical trials.

[Hypoxia promotes lipopolysaccharide-induced CXCL10 expression in microglia].

This study was aimed to investigate the effect of hypoxia on lipopolysaccharide (LPS)-induced CXC-chemokine ligand-10 (CXCL10) expression and the underlying mechanism. C57BL/6J mice were randomly divided into control, hypoxia, LPS, and hypoxia combined with LPS groups. The LPS group was intraperitoneally injected with 0.5 mg/kg LPS, and the hypoxia group was placed in a hypobaric hypoxia chamber (simulated altitude of 6 000 m). The serum and hippocampal tissue samples were collected after 6 h of the treatment. The levels of CXCL10 in the serum and hippocampal tissue of mice were detected by ELISA. The microglia cell line BV2 and primary microglia were stimulated with hypoxia (1% O2) and/or LPS (100 ng/mL) for 6 h. The mRNA expression level of CXCL10 and its content in culture supernatant were detected by real-time quantitative PCR and ELISA, respectively. The phosphorylation levels of nuclear factor κB (NF-κB) signaling pathway-related proteins, p65 and IκBα, were detected by Western blot. Moreover, after NF-κB signaling pathway being blocked with a small molecular compound, PDTC, CXCL10 mRNA expression level was detected in the BV2 cells. The results showed that in the LPS-induced mouse inflammatory model, hypoxia treatment could promote LPS-induced up-regulation of CXCL10 in both serum and hippocampus. Compared with the cells treated with LPS alone, the expression of CXCL10 mRNA and the content of CXCL10 in the culture supernatant of BV2 cells treated with hypoxia combined with LPS were significantly increased. The CXCL10 mRNA level of primary microglial cells treated with hypoxia combined with LPS was significantly up-regulated. Compared with the cells treated with hypoxia or LPS alone, the phosphorylation levels of p65 and IκBα in the BV2 cells treated with hypoxia combined with LPS were significantly increased. PDTC blocked the induction of CXCL10 gene expression by LPS in the BV2 cells. These results suggest that hypoxia promotes LPS-induced expression of CXCL10 in both animal and cell models, and NF-κB signaling pathway plays an important role in this process.

Mass spectrometry imaging: An emerging technology for the analysis of metabolites in insects.

Mass spectrometry imaging (MSI) can visualize the composition, abundance, and spatial distribution of molecules in tissues or cells, which has been widely used in the research of life science. Insects, especially the agricultural pests, have received a great deal of interests from the scientists in biodiversity and food security. This review introduces the major characteristics of MSI, summarizes its application to the investigation of insect endogenous metabolites, exogenous metabolites, and the spatiotemporal changes of metabolites between insects and plants, and discusses its shortfalls and perspectives. The significance of these concerns is beneficial for future insect research such as physiology and metabolism.

Differential Profiles of Gut Microbiota and Metabolites Associated with Host Shift of Plutella xylostella.

Evolutionary and ecological forces are important factors that shape gut microbial profiles in hosts, which can help insects adapt to different environments through modulating their metabolites. However, little is known about how gut microbes and metabolites are altered when lepidopteran pest species switch hosts. In the present study, using 16S-rDNA sequencing and mass spectrometry-based metabolomics, we analyzed the gut microbiota and metabolites of three populations of Plutella xylostella: one feeding on radish (PxR) and two feeding on peas (PxP; with PxP-1 and PxP-17 being the first and 17th generations after host shift from radish to peas, respectively). We found that the diversity of gut microbes in PxP-17 was significantly lower than those in PxR and PxP-1, which indicates a distinct change in gut microbiota after host shift. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the functions of energy metabolism, signal transduction, and xenobiotics biodegradation and metabolism were increased in PxP-17, suggesting their potential roles in host adaptation. Metabolic profiling showed a significant difference in the abundance of gut metabolites between PxR and PxP-17, and significant correlations of gut bacteria with gut metabolites. These findings shed light on the interaction among plants, herbivores, and symbionts, and advance our understanding of host adaptation associated with gut bacteria and metabolic activities in P. xylostella.

Identification of highly potent and selective PI3Kδ inhibitors.

Selective PI3Kδ inhibitors have recently been hypothesized to be appropriate immunosuppressive agents for the treatment of immunological disorders such as rheumatoid arthritis. However, few reports have highlighted molecules that are highly selective for PI3Kδ over the other PI3K isoforms. In this letter, isoform and kinome selective PI3Kδ inhibitors are presented. The Structural Activity Relationship leading to such molecules is outlined.

Purine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors for autoimmune diseases.

Investigation of various heterocyclic core isosteres of imidazopyrazines 1 & 2 yielded purine derivatives 3 & 8 as potent and selective BTK inhibitors. Subsequent SAR studies of the purine series led to the discovery of 20 as a leading compound. Compound 20 is very selective when screened against a panel of 400 kinases and is a potent inhibitor in cellular assays of human B cell function including B-Cell proliferation and CD86 cell surface expression and exhibited in vivo efficacy in a mouse PCA model. Its X-ray co-crystal structure with BTK shows that the high selectivity is gained from filling a BTK specific lipophilic pocket. However, physical and ADME properties leading to low oral exposure hindered further development.

Adolescent suicidal ideation: dissecting the role of sex in depression and NSSI predictors.

BACKGROUND: Suicidal ideation (SI) is increasingly prevalent among adolescents, often arising from depression and linked with non-suicidal self-injury (NSSI). Previous studies have noted significant sex differences in the manifestation and predictors of SI, depression, and NSSI. AIM: This study aims to analyze and compare the relationships between SI, depression, and NSSI among male and female adolescents, examining whether these associations differ based on sex. METHODS: A total of 368 adolescents (M = 15.43, SD = 1.22, about 56.2% female participants), both from clinical and school settings, were assessed for SI, depression, NSSI, and other related variables. Network analysis was utilized to explore the interconnections among these variables, focusing on identifying sex-specific patterns. Logistic regression was used to confirm the findings from the network analysis. RESULTS: The network analysis revealed significant sex differences in the relationships between SI, depression, and NSSI. In the female network, the edge weights between SI and NSSI (0.93) and between SI and depression (0.31) were much higher compared to the male network (0.29 and 0, respectively). Centrality indices (strength, betweenness, closeness, and expected influence) for SI, NSSI, and depression were also higher in the female network. Logistic regression confirmed these findings, with depression being a potential predictor of SI only in females (OR = 1.349, p = 0.001) and NSSI having a stronger influence on SI in females (OR = 13.673, p < 0.001) than in males (OR = 2.752, p = 0.037). CONCLUSION: The findings underscore the necessity of considering sex differences when predicting suicidal ideation from depression and NSSI in adolescents. Intervention and prevention strategies should be tailored to address these distinct patterns in male and female adolescents.

Alexithymia and peer victimisation: interconnected pathways to adolescent non-suicidal self-injury.

BACKGROUND: The prevalence of non-suicidal self-injury (NSSI) among adolescents underscores the importance of understanding the complex factors that drive this behaviour. Framed within broader constructs of emotional regulation theories, alexithymia and peer victimisation are thought to interact to influence NSSI behaviours. AIM: This research addresses whether alexithymia and peer victimisation serve as risk factors for NSSI and, if so, how these factors interact with each other. METHOD: This quantitative study analysed data from 605 adolescents, using a range of validated self-report measures including the Toronto Alexithymia Scale. Statistical analyses including one-way analysis of variance, multiple regression and structural equation modelling were employed to scrutinise the relationships among the variables. RESULTS: Alexithymia and peer victimisation significantly predicted NSSI behaviours. Specifically, the 'difficulty in identifying feelings' subscale of alexithymia emerged as a noteworthy predictor of NSSI (P < 0.001). Peer victimisation mediated the relationship between alexithymia and NSSI, explaining approximately 24.50% of alexithymia's total effect on NSSI. In addition, age was a significant predictor of NSSI, but gender and education years were not (P > 0.05). These relationships were found to be invariant across genders. CONCLUSIONS: This study enriches our understanding of the interplay between alexithymia, peer victimisation and NSSI, particularly within the Chinese context. Its findings have significant implications for a rethinking of alexithymia's theoretical construct and interventions targeting emotional literacy and peer dynamics among adolescents. Future research could benefit from a longitudinal design to establish causality.

Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials.

Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.

A network analysis of difficulties in emotion regulation, anxiety, and depression for adolescents in clinical settings.

BACKGROUND: Difficulties in emotion regulation (DER) are widely considered to underlie anxiety and depression. Given the prevalence of anxiety and depression in adolescents and the fact that adolescence is a key period for the development of emotion regulation ability, it is important to examine how DER is related to anxiety and depression in adolescents in clinical settings. METHODS: In the present study, we assessed 209 adolescents in clinical settings using the Difficulties in Emotion Regulation Scale (DERS) and the Hospital Anxiety and Depression Scale (HADS) and examined the associations between six components of DER and 14 symptoms of anxiety and depression. We used network analysis, constructed circular and multidimensional scaling (MDS) networks, and calculated network centrality, bridge centrality, and stability of centrality indices. RESULTS: The results showed that: (1) The global centrality index shows that the Strategy component (i.e., lack of access to strategies) is the center in the whole network, ranking highest in strength, closeness, betweenness, and expected influence. (2) The MDS network showed a closeness of anxiety and depression symptoms, while Awareness component (i.e., lack of emotional awareness) stayed away from other DER components, but Awareness is close to some depression symptoms. (3) The bridge nodes of three groups, Strategy from DERS, Worry and Relax from anxiety symptoms, and Cheerful and Slow from depression symptoms, had the strongest relationships with the other groups. CONCLUSION: Lack of access to strategies remains in the center not only in DER but also in the DER-anxiety-depression network, while lack of awareness is close to depression but not to anxiety. Worrying thoughts and inability to relax are the bridging symptoms for anxiety, while lack of cheerful emotions and slowing down are the bridging symptoms for depression. These findings suggest that making emotion regulation strategies more accessible to patients and reducing these bridging symptoms may yield the greatest rewards for anxiety and depression therapy.

Identification of Alfalfa SPL gene family and expression analysis under biotic and abiotic stresses.

The SQUAMOSA promoter binding-like protein (SPL) is a specific transcription factor that affects plant growth and development. The SPL gene family has been explored in various plants, but information about these genes in alfalfa is limited. This study, based on the whole genome data of alfalfa SPL, the fundamental physicochemical properties, phylogenetic evolution, gene structure, cis-acting elements, and gene expression of members of the MsSPL gene family were analyzed by bioinformatics methods. We identified 82 SPL sequences in the alfalfa, which were annotated into 23 genes, including 7 (30.43%) genes with four alleles, 10 (43.47%) with three, 3 (13.04%) with two, 3 (13.04%) with one allele. These SPL genes were divided into six groups, that are constructed from A. thaliana, M. truncatula and alfalfa. Chromosomal localization of the identified SPL genes showed arbitary distribution. The subcellular localization predictions showed that all MsSPL proteins were located in the nucleus. A total of 71 pairs of duplicated genes were identified, and segmental duplication mainly contributed to the expansion of the MsSPL gene family. Analysis of the Ka/Ks ratios indicated that paralogs of the MsSPL gene family principally underwent purifying selection. Protein-protein interaction analysis of MsSPL proteins were performed to predict their roles in potential regulatory networks. Twelve cis-acting elements including phytohormone and stress elements were detected in the regions of MsSPL genes. We further analyzed that the MsSPLs had apparent responses to abiotic stresses such as drought and salt and the biotic stress of methyl jasmonate. These results provide comprehensive information on the MsSPL gene family in alfalfa and lay a solid foundation for elucidating the biological functions of MsSPLs. This study also provides valuable on the regulation mechanism and function of MsSPLs in response to biotic and abiotic stresses.

The interplay of self-acceptance, social comparison and attributional style in adolescent mental health: cross-sectional study.

BACKGROUND: Adolescence is a pivotal stage vulnerable to mental health problems such as anxiety and depression. Although self-acceptance and social comparison are known to affect adolescent mental health, their interactive and moderating roles are not fully understood. AIMS: To explore the role of self-acceptance, social comparison and attributional style in predicting these mental health outcomes among adolescents in clinical settings. METHOD: A cross-sectional study was conducted on a sample of 242 adolescents. Participants completed measures assessing self-acceptance, social comparison, attributional style and mental health outcomes (depression and anxiety). Mediation models and multi-group analysis were used to examine the relationships among these variables. RESULTS: Our findings demonstrated a significant relationship between self-acceptance, social comparison, depression and anxiety (rs = 0.32-0.88). Specifically, lower self-acceptance and higher social comparison were associated with higher levels of depression and anxiety. Additionally, individuals with external attributional tendencies reported higher depression (Cohen's d = 0.61) and anxiety (d = 0.58) compared with those with internal tendencies. Mediation modelling showed that social comparison is a mediator between self-acceptance and depression (effect size -0.04, 95% CI -0.08 to -0.01) and anxiety (effect size -0.06, 95% CI -0.10 to -0.02). Crucially, multi-group analysis showed that the impact of social comparison on mental health outcomes varied significantly based on attributional style. CONCLUSIONS: These findings underscore the importance of considering self-acceptance, social comparison and attributional style in understanding and addressing mental health challenges during adolescence. This could inform the development of targeted interventions to promote mental health and well-being among adolescents. However, further research is needed to confirm these findings in diverse populations and to explore the underlying mechanisms in greater detail.

Network analysis of emotion regulation and reactivity in adolescents: identifying central components and implications for anxiety and depression interventions.

Difficulties in emotion regulation (DER) and emotion reactivity (ER) are important causes and consequences of psychiatric disorders such as depression and anxiety, and previous research suggests that there are many interactions between them. Understanding the structure of their relationship, and which components may play a key role, will help provide insight into emotion disorders in adolescents and provide guidance for clinical interventions. In this study, we collected data from 483 adolescents and used network analysis methods to explore the relationship between DER and ER, specifically looking for core nodes. The results showed that "limited access to emotion regulation strategies" was the most central node in the network. Furthermore, by adding nodes for depression and anxiety to this network, we found that anxiety had the strongest relationship with ER, while depression had a stronger relationship with DER. Thus, our findings suggest that for anxiety disorders, the strong association with ER highlights a potentially promising area for intervention development, whereas for depression, the association with DER points to the possibility of clarifying emotions and exploring coping strategies, acknowledging the complex interplay between depressive and anxious symptoms.

An engineered (CAGA)12-EGFP cell-based biosensor for high-content and accurate detection of active TGF-ß.

Transforming growth factor-ß (TGF-ß) regulates multiple fundamental physiological processes and is closely related to severe diseases such as cancer, fibrosis, immune disorders and cardiovascular diseases. TGF-ß is thus an important biomarker for clinical diagnosis and prognosis, and a crucial target for therapeutics development. Here we describe a high-content, serum-free, easy-to-use, and cost-effective (CAGA)12-EGFP cell-based biosensor for accurate measurements of active TGF-ß. Together with non-destructive and continuous measurement protocol and data processing method established here, the biosensor is capable of detecting active TGF-ß1 in the range of 0.024-6.25 ng/mL concentration with >91% accuracy and high repeatability. Overall, the engineered (CAGA)12-EGFP biosensor is a powerful tool for detection of active TGF-ß and for mechanistic study of the TGF-ß pathway. The greatly reduced cost and operating simplicity also makes it a highly potent in vitro platform for high-throughput screening of anti-TGF-ß therapeutics.

Lidocaine represses the malignant behavior of lung carcinoma cells via the circ_PDZD8/miR-516b-5p/GOLT1A axis.

Lung carcinoma is the most prevalent malignancy in adults. Lidocaine (Lido) has been confirmed to exert an anti-tumor role in many human cancers. However, the role and underlying mechanism of Lido in lung carcinoma remain poorly understood. Cell proliferation ability, migration, invasion, and apoptosis were measured by Colony formation, 5-ethynyl-2'-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), transwell, and flow cytometry assays. Circ_PDZD8, microRNA-516b-5p (miR-516b-5p), and Golgi transport 1A (GOLT1A) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Protein levels of proliferating cell nuclear antigen (PCNA) and GOLT1A were examined by western blot assay. The binding relationship between miR-516b-5p and circ_PDZD8 or GOLT1A was predicted by circular RNA Interactome or Starbase 3.0 and then verified by a dual-luciferase reporter assay. The biological roles of circ_PDZD8 and Lido on lung carcinoma cell growth were examined by the xenograft tumor model in vivo. Lido suppressed proliferation, migration, invasion, and induced apoptosis in lung carcinoma cells. Circ_PDZD8 and GOLT1A were increased, miR-516b-5p was decreased in lung carcinoma tissues and cell lines. Their expression presented the opposite trend in Lido-triggered lung carcinoma cells. Circ_PDZD8 might overturn the repression of Lido on cell growth ability and metastasis in this tumor. Mechanically, circ_PDZD8 might regulate GOLT1A expression by sponging miR-516b-5p. Circ_PDZD8 weakened the anti-lung carcinoma effect of Lido in vivo. Circ_PDZD8 might mitigate the inhibitory effect of Lido on tumor cell malignancy by modulating the miR-516b-5p/GOLT1A axis, providing a novel insight for lung carcinoma treatment.

Challenges for Artificial Intelligence in Recognizing Mental Disorders.

Artificial Intelligence (AI) appears to be making important advances in the prediction and diagnosis of mental disorders. Researchers have used visual, acoustic, verbal, and physiological features to train models to predict or aid in the diagnosis, with some success. However, such systems are rarely applied in clinical practice, mainly because of the many challenges that currently exist. First, mental disorders such as depression are highly subjective, with complex symptoms, individual differences, and strong socio-cultural ties, meaning that their diagnosis requires comprehensive consideration. Second, there are many problems with the current samples, such as artificiality, poor ecological validity, small sample size, and mandatory category simplification. In addition, annotations may be too subjective to meet the requirements of professional clinicians. Moreover, multimodal information does not solve the current challenges, and within-group variations are greater than between-group characteristics, also posing significant challenges for recognition. In conclusion, current AI is still far from effectively recognizing mental disorders and cannot replace clinicians' diagnoses in the near future. The real challenge for AI-based mental disorder diagnosis is not a technical one, nor is it wholly about data, but rather our overall understanding of mental disorders in general.

Genome-wide identification, phylogenetic, and expression analysis under abiotic stress conditions of Whirly (WHY) gene family in Medicago sativa L.

The WHY family is a group of plant-specific transcription factors, that can bind to single-stranded DNA molecules and play a variety of functions in plant nuclei and organelles, participating in the regulation of plant leaf senescence. It has been identified and analyzed in many species, however, the systematic identification and analysis of the WHY genes family have not yet been reported in alfalfa (Medicago sativa L.). Therefore, to explore the function of alfalfa the WHY genes, and 10 MsWHY genes were identified and further characterized their evolutionary relationship and expression patterns by analyzing the recently published genome of alfalfa. Comprehensive analysis of the chromosome location, physicochemical properties of the protein, evolutionary relationship, conserved motifs, and responses to abiotic stresses of the WHY gene family in alfalfa using bioinformatics methods. The results showed that 10 MsWHY genes were distributed on 10 chromosomes, and collinearity analysis showed that many MsWHYs might be derived from segmental duplications, and these genes are under purifying selection. Based on phylogenetic analyses, the WHY gene family of alfalfa can be divided into four subfamilies: I-IV subfamily, and approximately all the WHY genes within the same subfamily share similar gene structures. The 10 MsWHY gene family members contained 10 motifs, of which motif 2 and motif 4 are the conserved motifs shared by these genes. Furthermore, the analysis of cis-regulatory elements indicated that regulatory elements related to transcription, cell cycle, development, hormone, and stress response are abundant in the promoter sequence of the MsWHY genes. Real-time quantitative PCR demonstrated that MsWHYs gene expression is induced by drought, salt, and methyl jasmonate. The present study serves as a basic foundation for future functional studies on the alfalfa WHY family.

A network analysis of social problem-solving and anxiety/depression in adolescents.

Social problem-solving (SPS) involves the cognitive-behavioral processes through which an individual identifies and copes with everyday problems; it is considered to contribute to anxiety and depression. The Social Problem-Solving Inventory Revised is a popular tool measuring SPS problem orientations and problem-solving styles. Only a negative problem orientation (NPO) is considered strongly related to anxiety and depression. In the present study, we investigated the detailed connections among the five components of SPS and 14 anxiety-depression symptoms and specified the role of NPO and other components in the anxiety-depression network. We employed network analysis, constructed circular and multi-dimensional scaling (MDS) networks, and calculated the network centrality, bridge centrality, and stability of centrality indices. The results were as follows: (1) the MDS network showed a clustering of anxiety and depression symptoms, with NPO and avoidance style components from SPS being close to the anxiety-depression network (demonstrated by large bridge betweenness and bridge closeness); (2) the NPO and positive problem orientation from SPS were most influential on the whole network, though with an opposite effect; (3) strength was the most stable index [correlation stability (CS) coefficient = 0.516] among the centrality indices with case-dropping bootstraps. We also discussed this network from various perspectives and commented on the clinical implications and limitations of this study.