Dynamic Single-Cell RNA-Seq reveals mechanism of Selinexor-Resistance in Chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a type of hematologic malignancies caused by BCR-ABL chimeric oncogene. Resistance to tyrosine kinase inhibitors (TKIs) leads to the progression of CML into advanced stages. Selinexor is a small molecule inhibitor that targets a nuclear transporter called Exportin 1. Combined with imatinib, selinexor has been shown to disrupt nuclear-cytoplasmic transport signal of leukemia stem cells, resulting in cell death. The objective of this study was to investigate the mechanism of drug resistance to selinexor in CML. We established K562 cell line resistant to selinexor and conducted single cell dynamic transcriptome sequencing to analyze the heterogeneity within the parental and selinexor resistant cell populations. We identified specific gene expression changes associated with resistance to selinexor. Our results revealed differential expression patterns in genes such as MT2A, TFPI, MTND3, and HMGCS1 in the total RNA, as well as MT-TW, DNAJB1, and HSPB1 in the newly synthesized RNA, between the parental and drug-resistant groups. By applying pseudo-time analysis, we discovered that a specific cluster of cells exhibited characteristics of tumor stem cells. Furthermore, we observed a gradual decrease in the expression of ferroptosis-related molecules as drug resistance developed. In vitro experiments confirmed that the combination of a ferroptosis inducer called RSL3 effectively overcame drug resistance. In conclusion, this study revealed the resistance mechanism of selinexor in CML. In conclusion, we identified a subgroup of CML cells with tumor stem cell properties and demonstrated that ferroptosis inducer improved the efficacy of selinexor in overcoming drug resistance.

Kaempferol derivatives from Hippophae rhamnoides Linn. ameliorate H2O2-induced oxidative stress in SH-SY5Y cells by upregulating Nrf2.

As a medicinal and edible food, Hippophae rhamnoides Linn. subsp. sinensis Rousi is plenty of bioactive secondary metabolites including flavonoids and their derivatives, which have a certain protective effect on oxidative damage. The present study isolated three new kaempferol derivatives (compound 1-3), named Hippophandine A-C, from H. rhamnoides seed residue. The structures of Hippophandine A-C were explicated by HR-ESI-MS, NMR, and chemical analyses. Hippophandine A-C (1, 5, and 10 µM) were used to attenuate H2O2-induced cell death in SH-SY5Y and explore the mechanism in oxidative damage. The results elucidated that Hippophandine A-C reduced MDA, and increased the relative SOD, GSH, CAT contents, Nrf2 and HO-1 expression in H2O2-induced SH-SY5Y.

A Practical Tool for Measuring Home-Based Cardiac Rehabilitation Self-Management Behavior: A Multiphase Cross-Sectional Study.

BACKGROUND: Optimal self-management is the key to home-based cardiac rehabilitation for patients with heart disease. At present, there is a lack of a specific assessment tool to evaluate the home-based cardiac rehabilitation self-management behavior in patients with heart disease. Therefore, the aim of this study was to develop the Home-Based Cardiac Rehabilitation Self-Management Scale and validate its psychometric properties among patients with coronary heart disease. METHODS AND RESULTS: A multiphase cross-sectional study was conducted that study covered 3 phases: (1) item generation and revision, (2) item evaluation and preliminary exploration, and (3) assessment of the psychometric properties of the scale. A scale with 21 items was developed to measure the home-based cardiac rehabilitation self-management behavior. The content validity index of the scale was 0.980. In exploratory factor analysis, the 5-factor structure supported by eigenvalues and screen plot explained 74.326% of the total variation. In confirmatory factor analysis, all fitting indicators were acceptable, further supporting the construct validity of the scale. The criterion validity of the scale was 0.783. In the reliability analysis, the Cronbach's α coefficient of the scale was 0.882, with a dimensionality range of 0.780 to 0.936. The split-half reliability coefficient and test-retest reliability coefficient were 0.774 and 0.770, respectively. CONCLUSIONS: This study is the first to develop and validate a practical tool. This scale can comprehensively and accurately assess the self-management behavior of patients with heart disease in a home-based cardiac rehabilitation environment.

Isolation, Purification and Tyrosinase Inhibitory Activity of Anthocyanins and Their Novel Degradation Compounds from Solanum tuberosum L.

To explore the composition of anthocyanins and expand their biological activities, anthocyanins were systematically isolated and purified from tubers of Solanum tuberosum L., and their tyrosinase inhibitory activity was investigated. In this study, two new anthocyanin degradation compounds, norpetanin (9) and 4-O-(p-coumaryl) rhamnose (10), along with 17 known anthocyanins and their derivatives, were isolated and purified from an acid-ethanolic extract of fresh purple potato tubers. Their structures were elucidated via 1D and 2D NMR and HR-ESI-MS and compared with those reported in the literature. The extracts were evaluated for anthocyanins and their derivatives using a tyrosinase inhibitor screening kit and molecular docking technology, and the results showed that petanin, norpetanin, 4-O-(p-coumaryl) rhamnose, and lyciruthephenylpropanoid D/E possessed tyrosinase inhibitory activity, with 50% inhibiting concentration (IC50) values of 122.37 ± 8.03, 115.53 ± 7.51, 335.03 ± 12.99, and 156.27 ± 11.22 µM (Mean ± SEM, n = 3), respectively. Furthermore, petanin was validated against melanogenesis in zebrafish; it was found that it could significantly inhibit melanin pigmentation (p < 0.001), and the inhibition rate of melanin was 17% compared with the normal group. This finding may provide potential treatments for diseases with abnormal melanin production, and high-quality raw materials for whitening cosmetics.

E93 is indispensable for reproduction in ametabolous and hemimetabolous insects.

Ecdysone-induced protein 93 (E93), known as the "adult-specifier" transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. While E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discovered that in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNAs are broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we revealed that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.

Association between late bedtime and obesity in children and adolescents: a meta-analysis.

Background: Short sleep duration has been related to obesity in children and adolescents. However, it remains unknown whether late bedtime is also associated with obesity and whether the association is independent of sleep duration. A meta-analysis was performed to address this issue. Methods: In order to accomplish the aim of the meta-analysis, a comprehensive search was conducted on databases including PubMed, Embase, and Web of Science to identify observational studies. The cutoff to determine late bedtime in children in this meta-analysis was consistent with the value used among the included original studies. As for obesity, it was typically defined as a body mass index (BMI) > 95th percentile of age and sex specified reference standards or the International Obesity Task Force defined age- and gender-specific cut-off of BMI. The Cochrane Q test was employed to evaluate heterogeneity among the included studies, while the I2 statistic was estimated. Random-effects models were utilized to merge the results, considering the potential impact of heterogeneity. Results: Tweleve observational studies with 57,728 participants were included. Among them, 6,815 (11.8%) were obese. Pooled results showed that late bedtime reported by the participants or their caregivers was associated with obesity (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 1.16-1.39, p < 0.001; I2 = 0%). Subgroup analysis showed consistent results in studies with (OR: 1.33, 95% CI: 1.04-1.70, p = 0.02) and without adjustment of sleep duration (OR: 1.27, 95% CI: 1.14-1.41, p < 0.001). Further subgroup analysis also showed that the association was not significantly affected by study location, design, age of the participants, or diagnostic methods for obesity (p for subgroup difference all >0.05). Conclusion: Late bedtime is associated with obesity in children and adolescents, which may be independent of sleep duration.

Chloroplast genomes of Caragana tibetica and Caragana turkestanica: structures and comparative analysis.

BACKGROUND: The genus Caragana encompasses multiple plant species that possess medicinal and ecological value. However, some species of Caragana are quite similar in morphology, so identifying species in this genus based on their morphological characteristics is considerably complex. In our research, illumina paired-end sequencing was employed to investigate the genetic organization and structure of Caragana tibetica and Caragana turkestanica, including the previously published chloroplast genome sequence of 7 Caragana plants. RESULTS: The lengths of C. tibetica and C. turkestanica chloroplast genomes were 128,433 bp and 129,453 bp, respectively. The absence of inverted repeat sequences in these two species categorizes them under the inverted repeat loss clade (IRLC). They encode 110 and 111 genes (4 /4 rRNA genes, 30 /31tRNA genes, and 76 /76 protein-coding genes), respectively. Comparison of the chloroplast genomes of C. tibetica and C. turkestanica with 7 other Caragana species revealed a high overall sequence similarity. However, some divergence was observed between certain intergenic regions (matK-rbcL, psbD-psbM, atpA-psbI, and etc.). Nucleotide diversity (π) analysis revealed the detection of five highly likely variable regions, namely rps2-atpI, accD-psaI-ycf4, cemA-petA, psbN-psbH and rpoA-rps11. Phylogenetic analysis revealed that C. tibetica's sister species is Caragana jubata, whereas C. turkestanica's closest relative is Caragana arborescens. CONCLUSIONS: The present study provides worthwhile information about the chloroplast genomes of C. tibetica and C. turkestanica, which aids in the identification and classification of Caragana species.

Task-general or specific: The alertness modulates post-error adjustment.

Previous studies have shown that alertness is closely related to executive control function, but its impact on components of post-error adjustment is unknown. This study applied the Attentional Networks Test and the Four-choice Flanker task with three response stimulus intervals (RSIs) to explore the correlation between alertness and post-error adjustment. The linear mixed-effects model of alertness and RSI on the post-error processing indicators showed a significant negative correlation between the alertness and post-error slowing (PES) under 200 ms RSI , as well as between alertness and post-error improvement in accuracy (PIA) under both 700 ms RSI and 1200 ms RSI. Participants with lower alertness showed larger post-error slowing in the early stages, while those with higher alertness had smaller PIA in later stages. This study revealed the effects of alertness on different processing components of post-error adjustment. The control strategies utilized by individuals with high and low levels of alertness differed in preparation for performance monitoring. Alertness improved post-error response speed in a task-unspecific manner, but not post-error adaptation.

The neural dynamics of conflict adaptation induced by conflict observation: Evidence from univariate and multivariate analysis.

Conflict adaptation can be expressed as greater performance (shorter response time and lower error rate) after incongruent trials when compared to congruent trials. It has been observed in designs that minimize confounding factors, i.e., feature integration, contingency learning, and temporal learning. Our current study aimed to further elucidate the temporal evolution mechanisms of conflict adaptation. To address this issue, the current study employed a combination of behavioral, univariate, and multivariate analysis (MVPA) methods in a modified color-word Stroop task, where half of the trials required button presses (DO trials), and the other half only required observation (LOOK trials). Both behavioral and the ERP results (N450 and SP) in the LOOK-DO transition trials revealed significant conflict adaptation without feature integration, contingency learning, and temporal learning, providing support for the conflict monitoring theory. Furthermore, during the LOOK trials, significant Stroop effect in the N450 and SP components were observed, indicating that conflict monitoring occurred at the stimulus level and triggered reactive control adjustments. The MVPA results decoded the congruent-incongruent and incongruent-incongruent conditions during the conflict adjustment phase but not during the conflict monitoring phase, emphasizing the unique contribution of conflict adjustment to conflict adaptation. The current research findings provided more compelling supporting evidence for the conflict monitoring theory, while also indicating that future studies should employ the present design to elucidate the specific processes of conflict adaptation.

A subtype of schizophrenia patients with altered methylation level of genes related to immune cell activity.

BACKGROUND: Epigenetic changes are plausible molecular sources of clinical heterogeneity in schizophrenia. A subgroup of schizophrenia patients with elevated inflammatory or immune-dysregulation has been reported by previous studies. However, little is known about epigenetic changes in genes related to immune activation in never-treated first-episode patients with schizophrenia (FES) and its consistency with that in treated long-term ill (LTS) patients. METHODS: In this study, epigenome-wide profiling with a DNA methylation array was applied using blood samples of both FES and LTS patients, as well as their corresponding healthy controls. Non-negative matrix factorization (NMF) and k -means clustering were performed to parse heterogeneity of schizophrenia, and the consistency of subtyping results from two cohorts. was tested. RESULTS: This study identified a subtype of patients in FES participants (47.5%) that exhibited widespread methylation level alterations of genes enriched in immune cell activity and a significantly higher proportion of neutrophils. This clustering of FES patients was validated in LTS patients, with high correspondence in epigenetic and clinical features across two cohorts. CONCLUSIONS: In summary, this study demonstrated a subtype of schizophrenia patients across both FES and LTS cohorts, defined by widespread alterations in methylation profile of genes related to immune function and distinguishing clinical features. This finding illustrates the promise of novel treatment strategies targeting immune dysregulation for a subpopulation of schizophrenia patients.

Early Post-Transplant Adaptation Experience in Young and Middle-Aged People With Kidney Transplant in China: A Qualitative Study.

BACKGROUND: Successful adaptation to post-transplantation life in patients who have undergone kidney transplants is crucial. The psychosocial needs of people with kidney transplants are closely related to the health of the transplanted kidney. If transplant recipients cannot adapt to the effects of the transplant, their physical and mental health will be seriously impaired. OBJECTIVE: The purpose of this study was to explore the early post-transplant adaptation experience of young and middle-aged persons with kidney transplants in China based on the Roy adaptation model. METHODS: A qualitative descriptive study was conducted using semi-structured interviews. Fifteen young and middle-aged persons with kidney transplant were recruited from a tertiary hospital in China between September 2022 and March 2023 through purposive sampling. Data were analyzed using a thematic analysis approach. RESULTS: This study identified 4 themes: (1) "two-sided" changes in physiological functioning, (2) "dawn and darkness" (conflicting perceived emotions about the future), (3) role functioning adaptation conflict and impairment, and (4) social isolation and the challenges of coping. CONCLUSIONS: This study found that early post-transplant adaptation in young and middle-aged people with kidney transplant included both positive and negative experiences, and these findings can provide new insights into research related to successful post-operative adaptation.

Deep learning-assisted mass spectrometry imaging for preliminary screening and pre-classification of psychoactive substances.

Currently, it is of great urgency to develop a rapid pre-classification and screening method for suspected drugs as the constantly springing up of new psychoactive substances. In most researches, psychoactive substances classification approaches depended on the similar chemical structures and pharmacological action with known drugs. Such approaches could not face the complicated circumstance of emerging new psychoactive substances. Herein, mass spectrometry imaging and convolutional neural networks (CNN) were used for preliminary screening and pre-classification of suspected psychoactive substances. Mass spectrometry imaging was performed simultaneously on two brain slices as one was from blank group and another one was from psychoactive substance-induced group. Then, fused neurotransmitter variation mass spectrometry images (Nv-MSIs) reflecting the difference of neurotransmitters between two slices were achieved through two homemade programs. A CNN model was developed to classify the Nv-MSIs. Compared with traditional classification methods, CNN achieved better estimation accuracy and required minimal data preprocessing. Also, the specific region on Nv-MSIs and weight of each neurotransmitter that affected the classification most could be unraveled by CNN. Finally, the method was successfully applied to assist the identification of a new psychoactive substance seized recently. This sample was identified as cannabinoids, which greatly promoted the screening process.

Integrated ultrastructural, physiological, transcriptomic, and metabolomic analysis uncovers the mechanisms by which nicotinamide alleviates cadmium toxicity in Pistia stratiotes L.

Exogenous nicotinamide (NIC) is a promising solution to relieve heavy metal (HM) toxicity in plants. Nonetheless, the underlying mechanisms involved remain poorly understood. As NIC addition (200 µM) can increase the tolerance of Pistia stratiotes L. to Cd stress (10 mg L-1), this strategy was subjected to integrated ultrastructural, physiological, transcriptomic, and metabolomic analysis to reveal the mechanisms involved. Exogenous NIC initiated a series of physiological, transcriptional, and metabolic responses that alleviated Cd damage. NIC addition improved Cd transfer from roots to leaves and reduced Cd damage in roots. The transported Cd to leaves did not induce further toxicity because it was abundantly compartmentalised in cell walls, which might be mediated by lignin synthesis. Moreover, NIC addition improved the repair of photosystem II in leaves under Cd stress by inducing key genes (e.g., chlorophyll A-B binding protein and PSII repair protein encoding genes), resulting in the restoration of Fv/Fm. In addition, antioxidant enzyme activities (e.g., peroxidase and catalase) and synthesis of antioxidants (e.g., stachydrine and curculigoside) were triggered to overcome oxidative stress. Our work paves the way for a deeper understanding of the mechanisms by which NIC alleviates HM toxicity in plants, providing a basis for improving phytoremediation.

Exploring the Potential Mechanisms of Action of Gentiana Veitchiorum Hemsl. Extract in the Treatment of Cholestasis using UPLC-MS/MS, Systematic Network Pharmacology, and Molecular Docking.

INTRODUCTION: Gentiana veitchiorum Hemsl. (GV) has a long history in Tibetan medicine for treating hepatobiliary disease cholestasis. However, the mechanisms mediating its efficacy in treating cholestasis have yet to be determined. AIM: To elucidate the mechanisms of action of GV in the treatment of cholestasis, an integrated approach combining ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis with network pharmacology was established. MATERIALS AND METHODS: A comprehensive analysis of the chemical composition of GV was achieved by UPLC-MS/MS. Subsequently, a network pharmacology method that integrated target prediction, a protein-protein interaction (PPI) network, gene set enrichment analysis, and a component- target-pathway network was established, and finally, molecular docking and experiments in vitro were conducted to verify the predicted results. RESULTS: Twenty compounds that were extracted from GV were identified by UPLC-MS/MS analysis. Core proteins such as AKT1, TNF, and IL6 were obtained through screening in the Network pharmacology PPI network. The Kyoto Encyclopedia of the Genome (KEGG) pathway predicted that GV could treat cholestasis by acting on signaling pathways such as TNF/IL-17 / PI3K-Akt. Network pharmacology suggested that GV might exert a therapeutic effect on cholestasis by regulating the expression levels of inflammatory mediators, and the results were further confirmed by the subsequent construction of an LPS-induced RAW 264.7 cell model. CONCLUSIONS: In this study, UPLC-MS/MS analysis, network pharmacology, and experiment validation were used to explore potential mechanisms of action of GV in the treatment of cholestasis.

Psychometric validation of the Psoriasis Symptom Scale, Functional Assessment of Chronic Illness Therapy-Fatigue and pain-Visual Analogue Scale in patients with generalized pustular psoriasis.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease associated with considerable patient burden. The Psoriasis Symptom Scale (PSS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and pain-Visual Analogue Scale (pain-VAS) are patient-reported outcomes (PROs) that have not yet been validated in patients with GPP. OBJECTIVES: To evaluate the psychometric properties of the PSS, FACIT-Fatigue and pain-VAS using data from Effisayil 1, a randomised trial of spesolimab in patients with moderate-to-severe GPP. METHODS: Inter-item correlations and confirmatory factor analysis (CFA) were performed using Week 1 data. Internal consistency was assessed with Cronbach's α coefficient using baseline and Week 1 data. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs); change data for the GPP Physician Global Assessment total score and pustulation subscore were used to define a stable population. Convergent validity was assessed at baseline and Week 1 using Spearman's rank-order correlations. Known-groups validity was measured by analysis of variance using Week 1 data. Ability to detect change from baseline to Week 1 was evaluated by analysis of covariance. RESULTS: Inter-item and item-to-total correlations were moderate or strong for most PSS and FACIT-Fatigue items. CFA demonstrated the unidimensionality of the PSS and FACIT-Fatigue, with high factor loadings for most items (PSS range, 0.75-0.94; FACIT-Fatigue range, 0.11-0.93) and acceptable fit statistics. Both scores demonstrated internal consistency (Cronbach's α, 0.71 and 0.95, respectively). The PSS, FACIT-Fatigue and pain-VAS demonstrated test-retest reliability (ICCs ≥0.70) and good evidence of convergent validity. Furthermore, the PROs could differentiate between known groups of varying symptom severity (range, p < 0.0001-0.0225) and detect changes in symptom severity from baseline to Week 1 (range, p < 0.0001-0.0002). CONCLUSIONS: Overall, these results support the reliability, validity and ability to detect change of the PSS, FACIT-Fatigue and pain-VAS as PROs in patients with GPP.

Chloroplast genome analyses of Caragana arborescens and Caragana opulens.

BACKGROUND: Numerous species within the genus Caragana have high ecological and medicinal value. However, species identification based on morphological characteristics is quite complicated in the genus. To address this issue, we analyzed complete plastid genome data for the genus. RESULTS: We obtained chloroplast genomes of two species, Caragana arborescens and Caragana opulens, using Illumina sequencing technology, with lengths of 129,473 bp and 132,815 bp, respectively. The absence of inverted repeat sequences in the two species indicated that they could be assigned to the inverted repeat-lacking clade (IRLC). The genomes included 111 distinct genes (4 rRNA genes, 31 tRNA genes, and 76 protein-coding genes). In addition, 16 genes containing introns were identified in the two genomes, the majority of which contained a single intron. Repeat analyses revealed 129 and 229 repeats in C. arborescens and C. opulens, respectively. C. arborescens and C. opulens genomes contained 277 and 265 simple sequence repeats, respectively. The two Caragana species exhibited similar codon usage patterns. rpl20-clpP, rps19-rpl2, and rpl23-ycf2 showed the highest nucleotide diversity (pi). In an analysis of sequence divergence, certain intergenic regions (matK-rbcL, psbM-petN, atpA-psbI, petA-psbL, psbE-petL, and rps7-rps12) were highly variable. A phylogenetic analysis showed that C. arborescens and C. opulens were related and clustered together with four other Caragana species. The genera Astragalus and Caragana were relatively closely related. CONCLUSIONS: The present study provides valuable information about the chloroplast genomes of C. arborescens and C. opulens and lays a foundation for future phylogenetic research and molecular marker development.

Correlation of endolymphatic hydrops and perilymphatic enhancement with the clinical features of Ménière's disease.

OBJECTIVES: To use three-dimensional real inversion recovery (3D-real IR) MRI to investigate correlations between endolymphatic hydrops (EH) grades or the degree of perilymphatic enhancement (PE) and clinical features of Ménière's disease (MD), as previous findings have been inconsistent. METHODS: A total of 273 consecutive patients with definite unilateral MD were retrospectively enrolled from September 2020 to October 2021. All patients underwent 3D-real IR and 3D-T2WI 6 h after intravenous gadolinium injection. MD-related symptom duration and vertigo frequency were recorded. EH grades were evaluated, the signal intensity ratio (SIR) was measured, and correlations between clinical features and EH, PE were assessed respectively. RESULTS: The study included 123 males and 150 females, with a mean age of 53.0 years. A longer duration of vertigo was associated with higher cochlear EH grades, whereas the opposite was true for the duration of aural fullness. A longer time since vertigo onset was associated with higher vestibular EH grades; the opposite was true for the duration of individual vertigo attacks. The multiple regression analysis revealed that age, tinnitus duration, and vestibular EH were risk factors for SIR. Furthermore, the low-frequency hearing threshold (HT) was a risk factor for cochlear and vestibular EH, and the SIR. CONCLUSION: The EH grade and SIR (an indicator for the quantitative evaluation of PE) were correlated with clinical features and HT of MD; thus, imaging can be a valuable tool in planning individualised treatment. CLINICAL RELEVANCE STATEMENT: This study revealed that the grade of endolymphatic hydrops and degree of perilymphatic enhancement positively correlates with the length of time since onset of clinical symptoms and hearing thresholds in patients with Ménière's disease, facilitating the tailored treatment. KEY POINTS: • Relationships between 3-dimensional real inversion recovery features and clinical symptoms in Ménière's disease are unknown. • Symptom duration and hearing thresholds correlated with endolymphatic hydrops grades and degree of perilymphatic enhancement. • MRI features correlate with MD severity; thus, imaging is valuable for planning tailored treatment.

The Protein Response of Salt-Tolerant Zygosaccharomyces rouxii to High-Temperature Stress during the Lag Phase.

Zygosaccharomyces rouxii used in soy sauce brewing is an osmotolerant and halotolerant yeast, but it is not tolerant to high temperatures and the underlying mechanisms remain poorly understood. Using a synthetic medium containing only Pro as a nitrogen source, the response of Z. rouxii in protein level to high-temperature stress (40 °C, HTS) during the lag phase was investigated. Within the first two h, the total intracellular protein concentration was significantly decreased from 220.99 ± 6.58 µg/mg DCW to 152.63 ± 10.49 µg/mg DCW. The analysis of the amino acid composition of the total protein through vacuum proteolysis technology and HPLC showed that new amino acids (Thr, Tyr, Ser, and His) were added to newborn protein over time during the lag phase under HTS. The nutritional conditions used in this study determined that the main source of amino acid supply for protein synthesis was through amino acid biosynthesis and ubiquitination-mediated protein degradation. Differential expression analysis of the amino acid biosynthesis-related genes in the transcriptome showed that most genes were upregulated under HTS, excluding ARO8, which was consistently repressed during the lag phase. RT-qPCR results showed that high-temperature stress significantly increased the upregulation of proteolysis genes, especially PSH1 (E3 ubiquitin ligase) by 13.23 ± 1.44 fold (p < 0.0001) within 4 h. Overall, these results indicated that Z. rouxii adapt to prolonged high temperatures stress by altering its basal protein composition. This protein renewal was related to the regulation of proteolysis and the biosynthesis of amino acids.

Efficacy of Noninvasive Brain Stimulation in Treating General Psychopathology Symptoms in Schizophrenia: A Meta-Analysis.

OBJECTIVES: Noninvasive brain stimulation (NIBS) has been shown to effectively alleviate negative and positive symptoms in patients with schizophrenia. However, its impact on depressive symptoms and general psychopathology symptoms (GPSs), which are crucial for functional outcomes, remains uncertain. We aimed to compare the efficacy of various NIBS interventions in treating depressive symptoms and GPSs. METHODS: We conducted a comprehensive search of multiple databases and performed a meta-analysis to evaluate the efficacy of NIBS in treating depressive symptoms and GPSs in schizophrenia. The effect sizes of NIBS for depression symptoms and GPSs were estimated using standard mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses were employed to examine potential influencing factors on the pooled SMD of NIBS for GPSs. RESULTS: Our search yielded 35 randomized controlled trials involving 1715 individuals diagnosed with schizophrenia. The protocol of this systematic review was registered with INPLASY (protocol ID: INPLASY202320082). Neither repetitive transcranial magnetic stimulation (rTMS) nor transcranial direct current stimulation (tDCS) demonstrated significant improvements in depressive symptoms compared to sham controls. NIBS exhibited a small-to-moderate effect size for GPSs, with a pooled SMD of -0.2956 (95% CI: -0.459 to -0.132) and a heterogeneity (I2) of 58.9% (95% CI: 41.5% to 71.1%; p < 0.01) based on a random-effects model. Subgroup analyses of different types of NIBS, different frequencies of rTMS, and different stimulation sites of rTMS revealed no significant differences. Only sex had a significant influence on the effect size of NIBS for general psychopathology symptoms (p < 0.05). However, rTMS might be superior to tDCS, and high-frequency rTMS outperformed low-frequency rTMS in treating GPSs. CONCLUSIONS: We found a small-to-moderate effect size of NIBS in alleviating GPSs in patients with schizophrenia. Both rTMS and tDCS were more effective than sham stimulation in reducing GPSs in schizophrenia. The frequency used was associated with rTMS efficacy for GPSs.