Bioorthogonal labeling and profiling of N6-isopentenyladenosine (i6A) modified RNA.

Chemical modifications in RNAs play crucial roles in diversifying their structures and regulating numerous biochemical processes. Since the 1990s, several hydrophobic prenyl-modifications have been discovered in various RNAs. Prenyl groups serve as precursors for terpenes and many other biological molecules. The processes of prenylation in different macromolecules have been extensively studied. We introduce here a novel chemical biology toolkit that not only labels i6A, a prenyl-modified RNA residue, by leveraging the unique reactivity of the prenyl group, but also provides a general strategy to incorporate fluorescence functionalities into RNAs for molecular tracking purposes. Our findings revealed that iodine-mediated cyclization reactions of the prenyl group occur rapidly, transforming i6A from a hydrogen-bond acceptor to a donor. Based on this reactivity, we developed an Iodine-Mediated Cyclization and Reverse Transcription (IMCRT) tRNA-seq method, which can profile all nine endogenous tRNAs containing i6A residues in Saccharomyces cerevisiae with single-base resolution. Furthermore, under stress conditions, we observed a decline in i6A levels in budding yeast, accompanied by significant decrease of mutation rate at A37 position. Thus, the IMCRT tRNA-seq method not only permits semi-quantification of i6A levels in tRNAs but also holds potential for transcriptome-wide detection and analysis of various RNA species containing i6A modifications.

Aberrant effort-based reward dynamics in anhedonia.

Anhedonia is a transdiagnostic symptom and associated with a spectrum of reward deficits among which the motivational dysfunction is poorly understood. Previous studies have established the abnormal cost-benefit trade-off as a contributor to motivational deficits in anhedonia and its relevant psychiatric diseases. However, it remains elusive how the anhedonic neural dynamics underlying reward processing are modulated by effort expenditure. Using an effort-based monetary incentive delay task, the current event-related potential study examined the neural dynamics underlying the effort-reward interplay in anhedonia using a nonclinical sample who scored high or low on an anhedonia questionnaire. We found that effort prospectively decreased reward effect on the contingent variation negativity and the target-P3 but retrospectively enhanced outcome effect on the feedback-P3 following effort expenditure. Compared to the low-anhedonia group, the high-anhedonia group displayed a diminished effort effect on the target-P3 during effort expenditure and an increased effort-enhancement effect for neutral trials during the feedback-P3 period following effort expenditure. Our findings suggest that anhedonia is associated with an inefficient control and motivation allocation along the efforted-based reward dynamics from effort preparation to effort production.

Strengthened Interficial Adhesive Fracture Energy by Young's Modulus Matching Degree Strategy in Carbon-Based HTM Free MAPbI3 Perovskite Solar Cell with Enhanced Mechanical Compatibility.

Carbon-based hole transport layer-free perovskite solar cells (PSCs) based on methylammonium lead triiodide (MAPbI3 ) have become one of the research focus due to low cost, easy preparation, and good optoelectronic properties. However, instability of perovskite under vacancy defects and stress-strain makes it difficult to achieve high-efficiency and stable power output. Here, a soft-structured long-chain 2D pentanamine iodide (abbreviated as "PI") is used to improve perovskite quality and interfacial mechanical compatibility. PI containing CH3 (CH2 )4 NH3 + and I- ions not only passivate defects at grain boundaries, but also effectively alleviate residual stress during high temperature annealing via decreasing Young's modulus of perovskite film. Most importantly, PI effectively increases matching degree of Young's modulus between MAPbI3 (47.1 GPa) and carbon (6.7 GPa), and strengthens adhesive fracture energy (Gc ) between perovskite and carbon, which is helpful for outward release of nascent interfacial stress generated under service conditions. Consequently, photoelectric conversion efficiency (PCE) of optimal device is enhanced from 10.85% to 13.76% and operational stability is also significantly improved. 83.1% output is maintained after aging for 720 h at room temperature and 25-60% relative humidity (RH). This strategy of regulation from chemistry and physics provides a strategy for efficient and stable carbon-based PSCs.

Activation of HAND2-FGFR signaling pathway by lncRNA HAND2-AS1 in adenomyosis†.

Heart and neural crest derivatives expressed transcript 2 (HAND2) is a critical mediator of progesterone action in endometrial stromal cells. Silencing of Hand2 expression in mouse uterus leads to an unopposed FGFR-mediated action that causes female mice infertility. To investigate the involvement of HAND2-FGFR signaling in pathogenesis of adenomyosis, immunohistochemistry, in situ hybridization, and quantitative real-time PCR were employed to assess gene expression in the normal endometrium, the paired eutopic endometrium and ectopic lesions obtained from women with adenomyosis. DNA methylation in the regions of HAND2 promoter and the first exon was also monitored in these samples. Our results revealed that HAND2 expression were dramatically reduced, but FGF9 expression and FGFR-ERK1/2-mediated MAPK signaling pathway were enhanced in the eutopic endometrium and ectopic lesions of patients with adenomyosis compared to the normal controls. Interestingly, expression of HAND2-AS1, a long noncoding RNA that resides adjacent to HAND2 in genome, was also reduced in adenomyosis. DNA methylation analysis revealed that the bidirectional promoter between HAND2 and HAND2-AS1, and the first exon of HAND2 gene was heavily methylated in the eutopic endometrium and the ectopic lesions of adenomyosis. To investigate the regulation of gene expression by HAND2-AS1, HAND2-AS1 expression was silenced in human endometrial stromal cells. In contrast to the downregulation of HAND2 in response to HAND2-AS1 silencing, FGF9 expression was augmented significantly. Endometrial stromal cells lacking HAND2-AS1 exhibited enhanced proliferation and migration potentials. Collectively, our studies revealed a new molecular mechanism by which HAND2-AS1 is involved in the pathogenesis of adenomyosis via modulating HAND2-FGFR-mediated signaling.

MiR-182-5p: A Novel Biomarker in the Treatment of Depression in CSDS-Induced Mice.

BACKGROUND: Depression is a neuropsychiatric disease with a high disability rate and mainly caused by the chronic stress or genetic factors. There is increasing evidence that microRNAs (miRNAs) play a critical role in the pathogenesis of depression. However, the underlying molecular mechanism for the pathophysiology of depression of miRNA remains entirely unclear so far. METHODS: We first established a chronic social defeat stress (CSDS) mice model of depression, and depression-like behaviors of mice were evaluated by a series of behavioral tests. Next, we detected several abundantly expressive miRNAs suggested in previous reports to be involved in depression and found miR-182-5p was selected as a candidate for analysis in the hippocampus. Then western blotting and immunofluorescence were used together to examine whether adeno-associated virus (AAV)-siR-182-5p treatment alleviated chronic stress-induced decrease in hippocampal Akt/GSK3ß/cAMP-response element binding protein (CREB) signaling pathway and increase in neurogenesis impairment and neuroinflammation. Furthermore, CREB inhibitor was adopted to examine if blockade of Akt/GSK3ß/CREB signaling pathway abolished the antidepressant actions of AAV-siR-182-5p in mice. RESULTS: Knockdown of miR-182-5p alleviated depression-like behaviors and impaired neurogenesis of CSDS-induced mice. Intriguingly, the usage of agomiR-182-5p produced significant increases in immobility times and aggravated neuronal neurogenesis damage of mice. More importantly, it suggested that 666-15 blocked the reversal effects of AAV-siR-182-5p on the CSDS-induced depressive-like behaviors in behavioral testing and neuronal neurogenesis within hippocampus of mice. CONCLUSIONS: These findings indicated that hippocampal miR-182-5p/Akt/GSK3ß/CREB signaling pathway participated in the pathogenesis of depression, and it might give more opportunities for new drug developments based on the miRNA target in the clinic.

Integrated multi-omics analyses revealed the association between rheumatoid arthritis and colorectal cancer: MYO9A as a shared gene signature and an immune-related therapeutic target.

BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.

Association of persistent musculoskeletal pain with dementia risk score in adults aged 45 years or older: The China health and retirement longitudinal study.

BACKGROUND: Recent studies have confirmed an association between pain and dementia. Whether musculoskeletal pain in the spine, upper limbs, and lower limbs is associated with dementia risk remains unclear. The longitudinal effect of musculoskeletal pain on dementia risk also remains unclear. AIMS: This work aimed to investigate the association between musculoskeletal pain and dementia risk score. METHODS: We conducted cross-sectional and longitudinal analyses using data from the China Health and Retirement Longitudinal Study. Participants aged 45 years or older were recruited in 2011. A total of 10,759 participants with complete pain information at baseline were eligible for the cross-sectional analysis, and 5,855 were eligible for the longitudinal analyses. We utilized the Rotterdam Study Basic Dementia Risk Model (BDRM) to assess dementia risk. Generalized estimating equations were used to investigate the associations. RESULTS: Compared with participants without persistent musculoskeletal pain, those with persistent musculoskeletal pain (standardized, ß = 0.83; 95 % CI: 0.06, 1.61, p = 0.036), multisite pain (sites≧5; ß = 1.52; 95 % CI: 0.13, 2.91, p = 0.032), neck pain (ß = 2.33; 95 % CI: 0.41, 4.25, p = 0.018), back pain (ß = 2.12; 95 % CI: 0.43, 3.82, p = 0.014), waist pain (ß = 1.09; 95 % CI: 0.07, 2.11, p = 0.037), shoulder pain (ß = 1.74; 95 % CI: 0.46, 3.02, p = 0.008), wrist pain (ß = 2.72; 95 % CI: 0.42, 5.02, p = 0.021), and knee pain (ß = 1.91; 95 % CI: 0.70, 3.13, p = 0.002) had a higher BDRM score during 4 years of follow-up. CONCLUSIONS: Promoting the management of musculoskeletal pain may be beneficial in reducing the dementia risk score.

Disfunction of dorsal raphe nucleus-hippocampus serotonergic-HTR3 transmission results in anxiety phenotype of Neuroplastin 65-deficient mice.

Anxiety disorders are the most common psychiatric condition, but the etiology of anxiety disorders remains largely unclear. Our previous studies have shown that neuroplastin 65 deficiency (NP65-/-) mice exhibit abnormal social and mental behaviors and decreased expression of tryptophan hydroxylase 2 (TPH2) protein. However, whether a causal relationship between TPH2 reduction and anxiety disorders exists needs to be determined. In present study, we found that replenishment of TPH2 in dorsal raphe nucleus (DRN) enhanced 5-HT level in the hippocampus and alleviated anxiety-like behaviors. In addition, injection of AAV-NP65 in DRN significantly increased TPH2 expression in DRN and hippocampus, and reduced anxiety-like behaviors. Acute administration of exogenous 5-HT or HTR3 agonist SR57227A in hippocampus mitigated anxiety-like behaviors in NP65-/- mice. Moreover, replenishment of TPH2 in DRN partly repaired the impairment of long-term potentiation (LTP) maintenance in hippocampus of NP65-/- mice. Finally, we found that loss of NP65 lowered transcription factors Lmx1b expression in postnatal stage and replenishment of NP65 in DRN reversed the decrease in Lmx1b expression of NP65-/- mice. Together, our findings reveal that NP65 deficiency induces anxiety phenotype by downregulating DRN-hippocampus serotonergic-HTR3 transmission. These studies provide a novel and insightful view about NP65 function, suggesting an attractive potential target for treatment of anxiety disorders.

Physical effort paradox during reward evaluation and links to perceived control.

Effort expenditure not only prospectively discounts the reward associated with it but also retrospectively adds the subjective value of reward, which is known as the effort paradox. This study aimed to resolve the effort paradox during reward evaluation through the critical lens of neural dynamics and its potential moderators. In total, 40 participants completed an effort-reward task wherein they exerted varying physical efforts to obtain an opportunity to win monetary rewards by active or passive decision-making. We found that after-effects of physical effort expenditure during reward evaluation unfolded as an effort paradox over time, manifesting itself as an effort discounting effect during the reward positivity (RewP) period but as an effort enhancement effect during the late positive potential (LPP) interval. Then, we found a dynamic balance between the discounting effect and the enhancement effect such that the more effort discounted the RewP at the early stage, the more effort increased the LPP at the late stage. Moreover, we observed that the effort-reward relationship was modulated by perceived control such that it increased the reward sensitivity effect and decreased the effort discounting effect. Together, our findings provide new insights into the neural mechanisms underlying the after-effects of physical effort exertion during reward evaluation.

Refractive associations with corneal biomechanical properties among young adults: a population-based Corvis ST study.

PURPOSE: To assess the associations of corneal biomechanical properties as measured by the Corvis ST with refractive errors and ocular biometry in an unselected sample of young adults. METHODS: A total of 1645 healthy university students underwent corneal biomechanical parameters measurement by the Corvis ST. The refractive status of the participants was measured using an autorefractor without cycloplegia. Ocular biometric parameters were measured using the IOL Master. RESULTS: After adjusting for the effect of age, sex, biomechanical-corrected intraocular pressure and central corneal thickness, axial length was significantly associated with A1 velocity (A1v, ß = -10.47), A2 velocity (A2v, ß = 4.66), A2 deflection amplitude (A2DeflA, ß = -6.02), HC deflection amplitude (HC-DeflA, ß = 5.95), HC peak distance (HC-PD, ß = 2.57), deformation amplitude ratio max (DA Rmax, ß = -0.36), Ambrósio's relational thickness to the horizontal profile (ARTh, ß = 0.002). For axial length / corneal radius ratio, only A1v (ß = -2.01), A1 deflection amplitude (A1DeflA, ß = 2.30), HC-DeflA (ß = 1.49), HC-PD (ß = -0.21), DA Rmax (ß = 0.07), stress-strain index (SSI, ß = -0.29), ARTh (ß < 0.001) were significant associates. A1v (ß = 23.18), HC-DeflA (ß = -15.36), HC-PD (ß = 1.27), DA Rmax (ß = -0.66), SSI (ß = 3.53), ARTh (ß = -0.02) were significantly associated with spherical equivalent. CONCLUSION: Myopic eyes were more likely to have more deformable corneas and corneas in high myopia were easier to deform and were even softer compared with those in the mild/moderate myopia.

Distribution and determinants of corneal volume among healthy young Chinese adults: a cross-sectional study.

BACKGROUND: Several studies have previously reported the normal values of corneal volume (CV) in various populations, whereas little is known about the CV distribution in healthy young Chinese adults. Our study aimed to investigate the distribution of CV and its relationships with other ocular biometric parameters among healthy young Chinese adults. METHODS: A total of 1645 eyes from 1645 students at Dali University in Yunnan Province, China, were analyzed. Pentacam was used to measure CV. Central corneal thickness (CCT) and biomechanically corrected intraocular pressure (bIOP) were evaluated by Corvis-ST. Other biometrical parameters, including axial length (AL), keratometry, and white-to-white (WTW) distance, were measured using IOL Master. RESULTS: The mean age of the study population was 19.01 ± 0.92 years, and 68.81% of them were women. The CV was normally distributed in the whole sample, with a mean value of 61.23 ± 3.22 mm3. CV and CCT were significantly smaller in the Yi ethnic group than in the Han ethnic group (p < 0.01). CCT (coefficient: 0.085; p < 0.001) and keratometry (coefficient: 0.422; p < 0.001) were positively correlated with CV, while AL (coefficient: -0.204; p < 0.001), WTW distance (coefficient: -0.236; p < 0.001) and bIOP (coefficient: -0.06; p < 0.001) were inversely associated with CV. CONCLUSIONS: Our study provides an age-specific distribution of CV among healthy young Chinese adults. CCT, keratometry, AL, WTW distance and bIOP were important factors associated with CV.

Deficiency of ValRS-m Causes Male Infertility in Drosophila melanogaster.

Drosophila spermatogenesis involves the renewal of germline stem cells, meiosis of spermatocytes, and morphological transformation of spermatids into mature sperm. We previously demonstrated that Ocnus (ocn) plays an essential role in spermatogenesis. The ValRS-m (Valyl-tRNA synthetase, mitochondrial) gene was down-regulated in ocn RNAi testes. Here, we found that ValRS-m-knockdown induced complete sterility in male flies. The depletion of ValRS-m blocked mitochondrial behavior and ATP synthesis, thus inhibiting the transition from spermatogonia to spermatocytes, and eventually, inducing the accumulation of spermatogonia during spermatogenesis. To understand the intrinsic reason for this, we further conducted transcriptome-sequencing analysis for control and ValRS-m-knockdown testes. The differentially expressed genes (DEGs) between these two groups were selected with a fold change of ≥2 or ≤1/2. Compared with the control group, 4725 genes were down-regulated (dDEGs) and 2985 genes were up-regulated (uDEGs) in the ValRS-m RNAi group. The dDEGs were mainly concentrated in the glycolytic pathway and pyruvate metabolic pathway, and the uDEGs were primarily related to ribosomal biogenesis. A total of 28 DEGs associated with mitochondria and 6 meiosis-related genes were verified to be suppressed when ValRS-m was deficient. Overall, these results suggest that ValRS-m plays a wide and vital role in mitochondrial behavior and spermatogonia differentiation in Drosophila.

The impact of different states of type 2 diabetes when stratified by baseline HbA1c on the periodontal outcomes of non-surgical periodontal treatment: A systematic review and network meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been considered by many studies to have a bidirectional relationship with periodontitis. This systematic review and network meta-analysis aimed to investigate the impact of different states of T2DM when stratified by baseline HbA1c on the clinical outcomes of non-surgical periodontal treatment (NSPT). METHODS: This study followed the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines and involved an electronic literature search (from inception to the 2nd of January 2023). The study included at least two groups of patients: chronic periodontitis only (No-DM) or periodontitis and well-controlled/poorly controlled type 2 diabetes mellitus (WC/PC-T2DM). Clinical outcomes included probing depth (PD) reduction, bleeding on probing reduction, and clinical attachment level (CAL) gain. Direct and indirect comparisons between groups were assessed by network meta-analysis, thus allowing us to establish a treatment ranking. RESULTS: Ten prospective cohort studies (11 data sets) were included for qualitative analysis and network meta-analysis. The data included in this study had high consistency; in addition, a funnel plot and Egger's test showed that the articles had low publication bias. Network meta-analysis showed that the effect of NSPT in the No-DM group was significantly better than the WC-T2DM group [weighted mean difference (WMD) = 0.09, 95% confidence interval (CI) (0.01, 0.18)] and the PC-T2DM group [WMD = 0.09, 95% CI (0.01, 0.18)] in terms of CAL gain and better than the PC-T2DM group [WMD = 0.15, 95% CI (0.02, 0.28)] in terms of PD reduction. According to the surface under the cumulative ranking value, the No-DM group had the highest probability of achieving the best outcome following NSPT. CONCLUSIONS: Collectively, our analyses show that T2DM exerts significant effects on the outcomes of NSPT.

[Metabolomics of interventional effects of Coptidis Rhizoma and its processed products on oral ulcer due to excess heat in rats].

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.

Osa-miR535 targets SQUAMOSA promoter binding protein-like 4 to regulate blast disease resistance in rice.

Many rice microRNAs have been identified as fine-tuning factors in the regulation of agronomic traits and immunity. Among them, Osa-miR535 targets SQUAMOSA promoter binding protein-like 14 (OsSPL14) to positively regulate tillers but negatively regulate yield and immunity. Here, we uncovered that Osa-miR535 targets another SPL gene, OsSPL4, to suppress rice immunity against Magnaporthe oryzae. Overexpression of Osa-miR535 significantly decreased the accumulation of the fusion protein SPL4TBS -YFP that contains the target site of Osa-miR535 in OsSPL4. Consistently, Osa-miR535 mediated the cleavage of OsSPL4 mRNA between the 10th and 11th base pair of the predicted binding site at the 3' untranslated region. Transgenic rice lines overexpressing OsSPL4 (OXSPL4) displayed enhanced blast disease resistance accompanied by enhanced immune responses, including increased expression of defense-relative genes and up-accumulated H2 O2 . By contrast, the knockout mutant osspl4 exhibited susceptibility. Moreover, OsSPL4 binds to the promoter of GH3.2, an indole-3-acetic acid-amido synthetase, and promotes its expression. Together, these data indicate that Os-miR535 targets OsSPL4 and OsSPL4-GH3.2, which may parallel the OsSPL14-WRKY45 module in rice blast disease resistance.

Quantitative proteomics and phosphoproteomics reveal insights into mechanisms of ocnus function in Drosophila testis development.

BACKGROUND: Testis is the only organ supporting sperm production and with the largest number of proteins and tissue-specific proteins in animals. In our previous studies, we have found that knockdown of ocnus (ocn), a testis-specific gene, resulted in much smaller testis with no germ cells in Drosophila melanogaster. However, the molecular consequences of ocn knockdown in fly testes are unknown. RESULTS: In this study, through iTRAQ quantitative proteomics sequencing, 606 proteins were identified from fly abdomens as having a significant and at least a 1.5-fold change in expression after ocn knockdown in fly testes, of which 85 were up-regulated and 521 were down-regulated. Among the differential expressed proteins (DEPs), apart from those proteins involved in spermatogenesis, the others extensively affected biological processes of generation of precursor metabolites and energy, metabolic process, and mitochondrial transport. Protein-protein interaction (PPI) analyses of DEPs showed that several kinases and/or phosphatases interacted with Ocn. Re-analyses of the transcriptome revealed 150 differential expressed genes (DEGs) appeared in the DEPs, and their changing trends in expressions after ocn knockdown were consistent. Many common down-regulated DEGs and DEPs were testis-specific or highly expressed in the testis of D. melanogaster. Quantitative RT-PCR (qRT-PCR) confirmed 12 genes appeared in both DEGs and DEPs were significantly down-regulated after ocn knockdown in fly testes. Furthermore, 153 differentially expressed phosphoproteins (DEPPs), including 72 up-regulated and 94 down-regulated phosphorylated proteins were also identified (13 phosphoproteins appeared in both up- and down-regulated groups due to having multiple phosphorylation sites). In addition to those DEPPs associated with spermatogenesis, the other DEPPs were enriched in actin filament-based process, protein folding, and mesoderm development. Some DEPs and DEPPs were involved in Notch, JAK/STAT, and cell death pathways. CONCLUSIONS: Given the drastic effect of the ocn knockdown on tissue development and testis cells composition, the differences in protein abundance in the ocn knockdown flies might not necessarily be the direct result of differential gene regulation due to the inactivation of ocn. Nevertheless, our results suggest that the expression of ocn is essential for Drosophila testis development and that its down-regulation disturbs key signaling pathways related to cell survival and differentiation. These DEPs and DEPPs identified may provide significant candidate set for future studies on the mechanism of male reproduction of animals, including humans.

Electrocortical correlates of hypersensitivity to large immediate rewards in sensation seeking.

Sensation seeking and delay discounting are strong predictors of various risk-taking behaviors. However, the relationship between sensation seeking and delay discounting remains elusive. Here, we addressed this issue by examining how high sensation seekers (HSS; N = 40) and low sensation seekers (LSS; N = 40) evaluated immediate and delayed rewards with low and high amounts during a behavioral task and an EEG task of delay discounting. Although HSS and LSS exhibited comparable discounting preference at the behavioral level, HSS relative to LSS was associated with a greater delay discounting effect at the neural level when earned rewards were large. This abnormality of reward magnitude was further corroborated by an electrocortical hypersensitivity to large immediate rewards and a stronger neural coding of reward magnitude for HSS as compared to LSS. Our findings support both the hyperactive approach theory and the optimal arousal theory in sensation seeking and have implications for the prevention and intervention targeting sensation seeking to reduce maladaptive risk-taking behaviors.

Highly Enhanced Chloride Adsorption Mediates Efficient Neutral CO2 Electroreduction over a Dual-Phase Copper Catalyst.

Electrocatalytic carbon dioxide reduction (CO2R) in neutral electrolytes can mitigate the energy and carbon losses caused by carbonate formation but often experiences unsatisfied multicarbon selectivity and reaction rates because of the kinetic limitation to the critical carbon monoxide (CO)-CO coupling step. Here, we describe that a dual-phase copper-based catalyst with abundant Cu(I) sites at the amorphous-nanocrystalline interfaces, which is electrochemically robust in reducing environments, can enhance chloride-specific adsorption and consequently mediate local *CO coverage for improved CO-CO coupling kinetics. Using this catalyst design strategy, we demonstrate efficient multicarbon production from CO2R in a neutral potassium chloride electrolyte (pH ∼6.6) with a high Faradaic efficiency of 81% and a partial current density of 322 milliamperes per square centimeter. This catalyst is stable after 45 h of operation at current densities relevant to commercial CO2 electrolysis (300 mA per square centimeter).

Cellular and Intravital Imaging of NAD(P)H by a Red-Emitting Quinolinium-Based Fluorescent Probe that Features a Shift of Its Product from Mitochondria to the Nucleus.

NAD(P)H is a vital hydrogen donor and electron carrier involved in numerous biological processes. The development of small-molecule tools for intravital imaging of NAD(P)H is significant for further exploring their pathophysiological roles. Herein, we rationally designed a fluorescent probe NADH-R by a simple graft of pyridiniumylbutenenitrile on a 1-methylquinolinium moiety in the 3-position. Benefited from the reduction of quinolinium by NAD(P)H, this probe releases the free push-pull fluorophore NADH-RH, allowing a turn-on red-emitting fluorescence response together with an ultralow detection limit of 12 nM. Under the assistance of the probe, we first monitored exogenous and endogenous generation of NAD(P)H in living cells, subsequently observed dynamic changes of NAD(P)H levels in living cells under different metabolic perturbations, and finally visualized the declined NAD(P)H levels in live mouse brain in a stroke model. Unexpectedly, the time-dependent colocalization experiment revealed that the probe reacts with mitochondrial NAD(P)H, followed by a shift of its reduced product NADH-RH from mitochondria to the nucleus, highlighting that NADH-RH is a novel nucleus-directed dye scaffold, which would facilitate the development of nucleus-targeting fluorescent probes and drugs.

Neural dissociation between reward and salience prediction errors through the lens of optimistic bias.

The question of how the brain represents reward prediction errors is central to reinforcement learning and adaptive, goal-directed behavior. Previous studies have revealed prediction error representations in multiple electrophysiological signatures, but it remains elusive whether these electrophysiological correlates underlying prediction errors are sensitive to valence (in a signed form) or to salience (in an unsigned form). One possible reason concerns the loose correspondence between objective probability and subjective prediction resulting from the optimistic bias, that is, the tendency to overestimate the likelihood of encountering positive future events. In the present electroencephalography (EEG) study, we approached this question by directly measuring participants' idiosyncratic, trial-to-trial prediction errors elicited by subjective and objective probabilities across two experiments. We adopted monetary gain and loss feedback in Experiment 1 and positive and negative feedback as communicated by the same zero-value feedback in Experiment 2. We provided electrophysiological evidence in time and time-frequency domains supporting both reward and salience prediction error signals. Moreover, we showed that these electrophysiological signatures were highly flexible and sensitive to an optimistic bias and various forms of salience. Our findings shed new light on multiple presentations of prediction error in the human brain, which differ in format and functional role.