Morphological characterization and distribution of antennal sensilla of Spodoptera frugiperda (Lepidoptera: Noctuidae) using scanning electron microscopy.

The fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is a globally significant agricultural pest, causing severe damage to corn production in China. Chemical odor-based trapping is a major approach for FAW control, making it essential to understand the FAW antennal sensillum types to enhance development of effective chemical odor attractants. In this study, we comprehensively examined the antennal sensilla types of FAW, identifying eight types and two subtypes, including Böhm's bristles, sensilla trichoidea, sensilla chaetica (I and II), sensilla coeloconica, sensilla styloconica, sensilla squamiformia (I and II), sensilla auricillica, and sensilla basiconica. Sensilla chaetica II, and sensilla squamiformia II are reported for the first time for FAW in this study. Detailed low-voltage field emission scanning electron microscope (LVSEM) images and descriptions are provided for each sensillum type. This study provides the morphological information to aid in conducting antennal sensillum neurophysiological tests on FAW. RESEARCH HIGHLIGHTS: The types of sensilla of fall armyworm were examined, identifying eight types and two subtypes, including Böhm's bristles, sensilla trichoidea, sensilla chaetica (I and II), sensilla coeloconica, sensilla styloconica, sensilla squamiformia (I and II), sensilla auricillica, and sensilla basiconica. Detailed low-voltage field emission scanning electron microscope images and descriptions were provided for each sensillum type.

Cavity-Induced Optical Nonreciprocity Based on Degenerate Two-Level Atoms.

We developed and experimentally realized a scheme of optical nonreciprocity (ONR) by using degenerate two-level atoms embedded in an optical ring cavity. For the degenerate transition Fg = 4 ↔ Fe = 3, we first studied the cavity-transmission property in different coupling field configurations and verified that under the strong-coupling regime, the single-dark-state peak formed by electromagnetically induced transparency (EIT) showed ONR. The stable ground-state Zeeman coherence for Λ-chains involved in the degenerate two-level system was found to be important in the formation of intracavity EIT. However, different from the three-level atom-cavity system, in the degenerate two-level system, the ONR effect based on intracavity EIT occurred only at a low probe intensity, because the cavity-atom coupling strength was weakened in the counter-propagating probe and coupling field configuration. Furthermore, ONR transmission with a high contrast and linewidth-narrowing was experimentally demonstrated.

Disulfidptosis-associated LncRNA signature predicts prognosis and immune response in kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) represents a significant proportion of renal cell carcinomas and is characterized by high aggressiveness and poor prognosis despite advancements in immunotherapy. Disulfidptosis, a novel cell death pathway, has emerged as a critical mechanism in various cellular processes, including cancer. This study leverages machine learning to identify disulfidptosis-related long noncoding RNAs (DRlncRNAs) as potential prognostic biomarkers in KIRC, offering new insights into tumor pathogenesis and treatment avenues. RESULTS: Our analysis of data from The Cancer Genome Atlas (TCGA) led to the identification of 431 DRlncRNAs correlated with disulfidptosis-related genes. Five key DRlncRNAs (SPINT1-AS1, AL161782.1, OVCH1-AS1, AC131009.3, and AC108673.3) were used to develop a prognostic model that effectively distinguished between low- and high-risk patients with significant differences in overall survival and progression-free survival. The low-risk group had a favorable prognosis associated with a protective immune microenvironment and a better response to targeted drugs. Conversely, the high-risk group displayed aggressive tumor features and poor immunotherapy outcomes. Validation through qRT‒PCR confirmed the differential expression of these DRlncRNAs in KIRC cells compared to normal kidney cells, underscoring their potential functional significance in tumor biology. CONCLUSIONS: This study established a robust link between disulfidptosis-related lncRNAs and patient prognosis in KIRC, underscoring their potential as prognostic biomarkers and therapeutic targets. The differential expression of these lncRNAs in tumor versus normal tissue further highlights their relevance in KIRC pathogenesis. The predictive model not only enhances our understanding of KIRC biology but also provides a novel stratification tool for precision medicine approaches, improving treatment personalization and outcomes in KIRC patients.

OBHSA, a novel selective estrogen receptor degrader, overcomes tamoxifen resistance through cell cycle arrest and unfolded protein response-mediated apoptosis in breast cancer.

Breast cancer (BC) is a highly heterogeneous tumor that has surpassed lung cancer as the most frequently diagnosed cancer in women. In clinical practice,the primary approach for treating estrogen receptor alpha (ERα)-positive BC is through endocrine therapy, which involves targeting the ERα using medications like tamoxifen and fulvestrant. However, the problem of de novo or acquired resistance poses a significant clinical challenge, emphasizing the critical need for the development of novel therapeutic strategies. In this regard, we have successfully designed and developed a novel selective estrogen receptor degrader (SERD) called OBHSA, which specifically targets and degrades ERα, demonstrating remarkable efficacy. Our findings revealed the effectiveness of OBHSA in inhibiting the proliferation of various BC cells, including both tamoxifen-sensitive and tamoxifen-resistant BC cells, indicating its great potential to overcome endocrine resistance. In terms of mechanism, we discovered that OBHSA overcame tamoxifen resistance through two distinct pathways. Firstly, OBHSA degraded cyclin D1 in an ERα-dependent manner, thereby blocking the cell cycle. Secondly, OBHSA induced an elevation in intracellular reactive oxygen species, triggering an excessive activation of the unfolded protein response (UPR) and ultimately leading to apoptotic cell death. In summary, our finding demonstrated that OBHSA exerts anti-tumor effects by inducing cell cycle arrest and UPR-mediated apoptosis. These findings hold promise for the development of novel therapeutic drugs targeting endocrine-resistant BC.

Effect of esketamine on serum neurotransmitters in patients with postpartum depression: a randomized controlled trial.

BACKGROUND: The development of postpartum depression has been linked to fluctuations in the levels of neurotransmitters in the human body, such as 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (Norepinephrine, NE), and brain derived neurotrophic factor (BDNF). Research has indicated that the antidepressant effect of esketamine are mediated by monoamine transmitters and neurotrophic factors. Therefore, we postulate that intravenous administration of esketamine in patients with postpartum depression may alter the serum concentrations of these neurotransmitters. METHODS: Three hundred fifteen patients with postpartum depression were selected and divided into two groups based on randomized numerical expression: esketamine (E) group (0. 25 mg/kg esketamine) and control (C) group (a same volume of 0.9% saline), all the drugs were pumped for 40 min. After the end of drug pumping, all patients were continuously observed for 2 h. Changes in serum levels of 5-HT, DA, NE, BDNF were recorded before drug administration and on the 3rd day after drug administration. The scores of Edinburgh Postnatal Depression Scale (EPDS) were calculated before drug administration, and on the 3rd day and on the 30th day after drug administration. Dizziness, headache, nausea, vomiting, drowsiness, and feeling of detachment occurred were recorded within 2 h after drug administration. RESULTS: Before drug administration, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (0. 91 ± 0. 19 vs. 0. 98 ± 0. 21, P = 0. 181), (2. 38 ± 0. 35 vs. 2. 32 ± 0. 32, P = 0. 491), (3. 07 ± 0. 89 vs 3. 02 ± 0. 88, P = 0. 828), (39. 79 ± 7. 78 vs 41. 34 ± 10. 03, P = 0. 506). On the third day post-medication, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (1. 42 ± 0. 35 vs. 0. 96 ± 0. 24, P < 0. 001), (3. 99 ± 0. 17 vs. 2. 41 ± 0. 28, P < 0. 001),(5. 45 ± 0. 81 vs 3. 22 ± 0. 76, P < 0. 001),(44. 36 ± 9. 98 vs 40. 69 ± 11. 75, P = 0. 198). Before medication, the EPDS scores were (16. 15 ± 3. 02 vs 17. 85 ± 3. 89, P = 0. 064). on the third day after medication, the Group E had significantly reduced scores (12. 98 ± 2. 39 vs 16. 73 ± 3. 52, P < 0. 001). On the 30rd day after medication, EPDS scores between the two groups were (16. 34 ± 3. 43 vs 16. 91 ± 4. 02, p = 0. 203). Within 2 h of medication, the rate of adverse events was similar between the two groups. CONCLUSIONS: Small doses of esketamine can increase the serum concentration of 5-HT,DA,BDNF, and in the short term, decrease EPDS scores, and improve postpartum depressive symptoms. TRIAL REGISTRATION: Retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2300078343, 2023/12/05).

Effect of esketamine on hypotension in women with preoperative anxiety undergoing elective cesarean section: a randomized, double-blind, controlled trial.

To investigate the effect of low-doses esketamine on spinal anesthesia-induced hypotension in women with preoperative anxiety undergoing elective cesarean section, the randomized controlled trial enrolled 120 women aged 18-35 years who preoperative State-Trait Anxiety Inventory State scores > 40, conducted from September 2022 to August 2023 in Xuzhou Central Hospital, China. Women in the esketamine group received a single intravenous injection of 0.2 mg/kg esketamine after sensory block level achieved. The incidence of hypotension in the esketamine group was significantly lower than the control group at T2 (10% [6 of 60]; P < 0.001), T3 (5.0% [3 of 60]; P = 0.007) and T4(5.0% [3 of 60]; P = 0.004). Despite being higher in the esketamine group, the overall rates of hypertension (11.7% [7 of 60]; P = 0.186), tachycardia (23.3% [14 of 60]; P = 0.246), and bradycardia (0.0% [0 of 60]; P = 0.079) were no significantly difference between the two groups. STAI-S scores was significantly lower in the esketamine group (mean [SD] 37.52[7.14]) than in the control group (mean [SD] 41.03[9.66], P = 0.39) in postoperative day 1. Spinal anesthesia combined with intravenous low-doses esketamine infusion can significantly reduce the incidence of hypotension in women with preoperative anxiety undergoing elective cesarean section.

Two C-terminal isoforms of Aplysia tachykinin-related peptide receptors exhibit phosphorylation-dependent and phosphorylation-independent desensitization mechanisms.

Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their posttranslational modifications were observed in extracts of central nervous system ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (apTKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.

Exploring drug repositioning possibilities of kinase inhibitors via molecular simulation.

Kinases, a class of enzymes controlling various substrates phosphorylation, are pivotal in both physiological and pathological processes. Although their conserved ATP binding pockets pose challenges for achieving selectivity, this feature offers opportunities for drug repositioning of kinase inhibitors (KIs). This study presents a cost-effective in silico prediction of KIs drug repositioning via analyzing cross-docking results. We established the KIs database (278 unique KIs, 1834 bioactivity data points) and kinases database (357 kinase structures categorized by the DFG motif) for carrying out cross-docking. Comparative analysis of the docking scores and reported experimental bioactivity revealed that the Atypical, TK, and TKL superfamilies are suitable for drug repositioning. Among these kinase superfamilies, Olverematinib, Lapatinib, and Abemaciclib displayed enzymatic activity in our focused AKT-PI3K-mTOR pathway with IC50 values of 3.3, 3.2 and 5.8 µM. Further cell assays showed IC50 values of 0.2, 1.2 and 0.6 µM in tumor cells. The consistent result between prediction and validation demonstrated that repositioning KIs via in silico method is feasible.

Effects of Drought Stress on Leaf Functional Traits and Biomass Characteristics of Atriplex canescens.

Drought is a critical factor constraining plant growth in arid regions. However, the performance and adaptive mechanism of Atriplex canescens (A. canescens) under drought stress remain unclear. Hence, a three-year experiment with three drought gradients was performed in a common garden, and the leaf functional traits, biomass and biomass partitioning patterns of A. canescens were investigated. The results showed that drought stress had significant effects on A. canescens leaf functional traits. A. canescens maintained the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), but the peroxidase (POD) and catalase (CAT) activity decreased, and the content of proline (Pro) and soluble sugar (SS) increased only under heavy drought stress. Under drought stress, the leaves became smaller but denser, the specific leaf area (SLA) decreased, but the dry matter content (LDMC) maintained stability. Total biomass decreased 60% to 1758 g under heavy drought stress and the seed and leaf biomass was only 10% and 20% of non-stress group, but there had no significant difference on root biomass. More biomass was allocated to root under drought stress. The root biomass allocation ratio was doubled from 9.62% to 19.81% under heavy drought, and the root/shoot ratio (R/S) increased from 0.11 to 0.25. The MDA was significantly and negatively correlated with biomass, while the SPAD was significantly and positively correlated with total and aboveground organs biomass. The POD, CAT, Pro and SS had significant correlations with root and seed allocation ratio. The leaf morphological traits related to leaf shape and weight had significant correlations with total and aboveground biomass and biomass allocation. Our study demonstrated that under drought stress, A. canescens made tradeoffs between growth potential and drought tolerance and evolved with a conservative strategy. These findings provide more information for an in-depth understanding of the adaption strategies of A. canescens to drought stress and provide potential guidance for planting and sustainable management of A. canescens in arid and semi-arid regions.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma.

Hepatic artery infusion chemotherapy (HAIC) has good clinical efficacy in the treatment of advanced hepatocellular carcinoma (HCC); however, its efficacy varies. This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications. As of October 25, 2023, 51 articles have been retrieved based on keyword predictions and HAIC. Sixteen eligible articles were selected for inclusion in this study. Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing, gene testing, and imaging testing. The above indicators and their combined forms showed excellent predictive effects in retrospective studies. This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC, analyzed each marker's ability to predict HAIC efficacy, and provided a reference for the clinical application of the prediction system.

Residual and bidirectional LSTM for epileptic seizure detection.

Electroencephalogram (EEG) plays a pivotal role in the detection and analysis of epileptic seizures, which affects over 70 million people in the world. Nonetheless, the visual interpretation of EEG signals for epilepsy detection is laborious and time-consuming. To tackle this open challenge, we introduce a straightforward yet efficient hybrid deep learning approach, named ResBiLSTM, for detecting epileptic seizures using EEG signals. Firstly, a one-dimensional residual neural network (ResNet) is tailored to adeptly extract the local spatial features of EEG signals. Subsequently, the acquired features are input into a bidirectional long short-term memory (BiLSTM) layer to model temporal dependencies. These output features are further processed through two fully connected layers to achieve the final epileptic seizure detection. The performance of ResBiLSTM is assessed on the epileptic seizure datasets provided by the University of Bonn and Temple University Hospital (TUH). The ResBiLSTM model achieves epileptic seizure detection accuracy rates of 98.88-100% in binary and ternary classifications on the Bonn dataset. Experimental outcomes for seizure recognition across seven epilepsy seizure types on the TUH seizure corpus (TUSZ) dataset indicate that the ResBiLSTM model attains a classification accuracy of 95.03% and a weighted F1 score of 95.03% with 10-fold cross-validation. These findings illustrate that ResBiLSTM outperforms several recent deep learning state-of-the-art approaches.

The OsMYC2-JA feedback loop regulates diurnal flower-opening time via cell wall loosening in rice.

Diurnal flower-opening time (DFOT), the time of spikelet opening during the day, is an important trait for hybrid rice (Oryza sativa L.) seed production. Hybrids between indica and japonica rice varieties have strong heterosis, but the parental lines usually have different, nonoverlapping DFOTs. This reduces the success of hybrid seed production in crosses between indica and japonica subspecies, thus hindering the utilization of indica and japonica inter-subspecies heterosis. However, little is known about the molecular mechanisms regulating DFOT in rice. Here, we obtained japonica rice lines with a DFOT 1.5 h earlier than the wild type by overexpressing OsMYC2, a gene encoding a key transcription factor in the jasmonate (JA) signaling pathway. OsMYC2 is activated by JA signaling and directly regulates the transcription of genes related to JA biosynthesis and cell wall metabolism. Overexpressing OsMYC2 led to significantly increased JA contents and decreased cellulose and hemicellulose contents in lodicule cells, as well as the softening of lodicule cell walls. This may facilitate the swelling of lodicules, resulting in early diurnal flower-opening. These results suggest that the OsMYC2-JA feedback loop regulates DFOT in rice via cell wall remodeling. These findings shed light on the understanding of regulatory mechanism of the DFOT of plants, which should promote the development of indica and japonica varieties suitable for hybrid rice breeding.

C-reactive protein: structure, function, regulation, and role in clinical diseases.

C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions in vivo. The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases in vivo.

Fine and combinatorial regulation of key metabolic pathway for enhanced ß-alanine biosynthesis with non-inducible Escherichia coli.

ß-Alanine is the only ß-amino acid in nature and one of the most important three-carbon chemicals. This work was aimed to construct a non-inducible ß-alanine producer with enhanced metabolic flux towards ß-alanine biosynthesis in Escherichia coli. First of all, the assembled E. coli endogenous promoters and 5'-untranslated regions (PUTR) were screened to finely regulate the combinatorial expression of genes panDBS and aspBCG for an optimal flux match between two key pathways. Subsequently, additional copies of key genes (panDBS K104S and ppc) were chromosomally introduced into the host A1. On these bases, dynamical regulation of the gene thrA was performed to reduce the carbon flux directed in the competitive pathway. Finally, the ß-alanine titer reached 10.25 g/L by strain A14-R15, 361.7% higher than that of the original strain. Under fed-batch fermentation in a 5-L fermentor, a titer of 57.13 g/L ß-alanine was achieved at 80 h. This is the highest titer of ß-alanine production ever reported using non-inducible engineered E. coli. This metabolic modification strategy for optimal carbon flux distribution developed in this work could also be used for the production of various metabolic products.

Template Synthesis of Cyclometalated Macrocycle Iridium(III) Complexes Based on Photoinduced C-N Cross-Coupling Reactions In Situ.

The synthesis of metal macrocycle complexes holds paramount importance in coordination and supramolecular chemistry. Toward this end, we report a new, mild, and efficient protocol for the synthesis of cyclometalated macrocycle Ir(III) complexes: [Ir(L1)](PF6) (1), [Ir(L2)](PF6) (2), and [Ir(L3)](PF6) (3), where L1 presents 10,17-dioxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclooctadecaphane, L2 is 10,13,16,19,22,25-hexaoxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclohexacosaphane, and L3 is 4-methyl-10,13,16,19,22,25-hexaoxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclohexacosaphane. This synthesis involves the preassembly of two symmetric 2-phenylquinoline arms into C-shape complexes, followed by cyclization with diamine via in situ interligand C-N cross-coupling, employing a metal ion as a template. Moreover, the synthetic yield of these cyclometalated Ir(III) complexes, tethered by an 18-crown-6 ether-like chain, is significantly enhanced in the presence of K+ ion as a template. The resultant cyclometalated macrocycle Ir(III) complexes exhibit high stability, efficient singlet oxygen generation, and superior catalytic activity for the aerobic selective oxidation of sulfides into sulfoxides under visible light irradiation in aqueous media at room temperature. The photocatalyst 2 demonstrates recyclability and can be reused at least 10 times without a significant loss of catalytic activity. These results unveil a new and complementary approach to the design and in situ synthesis of cyclometalated macrocycle Ir(III) complexes via a mild interligand-coupling strategy.

Balancing High-performance and Lightweight: HL-UNet for 3D Cardiac Medical Image Segmentation.

RATIONALE AND OBJECTIVES: Cardiac magnetic resonance imaging is a crucial tool for analyzing, diagnosing, and formulating treatment plans for cardiovascular diseases. Currently, there is very little research focused on balancing cardiac segmentation performance with lightweight methods. Despite the existence of numerous efficient image segmentation algorithms, they primarily rely on complex and computationally intensive network models, making it challenging to implement them on resource-constrained medical devices. Furthermore, simplified models designed to meet the requirements of device lightweighting may have limitations in comprehending and utilizing both global and local information for cardiac segmentation. MATERIALS AND METHODS: We propose a novel 3D high-performance lightweight medical image segmentation network, HL-UNet, for application in cardiac image segmentation. Specifically, in HL-UNet, we propose a novel residual-enhanced Adaptive attention (REAA) module that combines residual-enhanced connectivity with an adaptive attention mechanism to efficiently capture key features of input images and optimize their representation capabilities, and integrates the Visual Mamba (VSS) module to enhance the performance of HL-UNet. RESULTS: Compared to large-scale models such as TransUNet, HL-UNet increased the Dice of the right ventricular cavity (RV), left ventricular myocardia (MYO), and left ventricular cavity (LV), the key indicators of cardiac image segmentation, by 1.61%, 5.03% and 0.19%, respectively. At the same time, the Params and FLOPs of the model decreased by 41.3 M and 31.05 G, respectively. Furthermore, compared to lightweight models such as the MISSFormer, the HL-UNet improves the Dice of RV, MYO, and LV by 4.11%, 3.82%, and 4.33%, respectively, when the number of parameters and computational complexity are close to or even lower. CONCLUSION: The proposed HL-UNet model captures local details and edge information in images while being lightweight. Experimental results show that compared with large-scale models, HL-UNet significantly reduces the number of parameters and computational complexity while maintaining performance, thereby increasing frames per second (FPS). Compared to lightweight models, HL-UNet shows substantial improvements across various key metrics, with parameter count and computational complexity approaching or even lower.

Causal relationships between gut microbiota and dementia: A two-sample, bidirectional, Mendelian randomization study.

BACKGROUND: Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia, including Alzheimer's dementia, vascular dementia, and dementia in other diseases classified elsewhere. However, the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear. AIM: To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization (MR) analysis. METHODS: A bidirectional, two-sample, MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study (GWAS) summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium. Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the F-statistic. Five MR methods were employed, and the robustness of our findings was validated. To account for multiple comparisons, we applied the Bonferroni method for P-value adjustment. RESULTS: We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes, potentially serving as risk or protective factors for the disease. In addition, reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes. An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy. After applying correction for multiple testing, we observed that the order Bacillales (odds ratio: 0.830, 95% confidence interval: 0.740-0.932, P = 0.00155, Padjust = 0.0311) exhibited a strong association with Alzheimer's disease-related dementia. CONCLUSION: The results suggest that gut microbiota is causally associated with dementia. Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.

The Identification and Gene Mapping of Spotted Leaf Mutant spl43 in Rice.

Our study investigates the genetic mechanisms underlying the spotted leaf phenotype in rice, focusing on the spl43 mutant. This mutant is characterized by persistent reddish-brown leaf spots from the seedling stage to maturity, leading to extensive leaf necrosis. Using map-based cloning, we localized the responsible locus to a 330 Kb region on chromosome 2. We identified LOC_Os02g56000, named OsRPT5A, as the causative gene. A point mutation in OsRPT5A, substituting valine for glutamic acid, was identified as the critical factor for the phenotype. Functional complementation and the generation of CRISPR/Cas9-mediated knockout lines in the IR64 background confirmed the central role of OsRPT5A in controlling this trait. The qPCR results from different parts of the rice plant revealed that OsRPT5A is constitutively expressed across various tissues, with its subcellular localization unaffected by the mutation. Notably, we observed an abnormal accumulation of reactive oxygen species (ROS) in spl43 mutants by examining the physiological indexes of leaves, suggesting a disruption in the ROS system. Complementation studies indicated OsRPT5A's involvement in ROS homeostasis and catalase activity regulation. Moreover, the spl43 mutant exhibited enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo), highlighting OsRPT5A's role in rice pathogen resistance mechanisms. Overall, our results suggest that OsRPT5A plays a critical role in regulating ROS homeostasis and enhancing pathogen resistance in rice.

Adolescent administration of ketamine impairs excitatory synapse formation onto parvalbumin-positive GABAergic interneurons in mouse prefrontal cortex.

Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, induces deficits in cognition and information processing following chronic abuse. Adolescent ketamine misuse represents a significant global public health issue; however, the neurodevelopmental mechanisms underlying this phenomenon remain largely elusive. This study investigated the long-term effects of sub-chronic ketamine (Ket) administration on the medial prefrontal cortex (mPFC) and associated behaviors. In this study, Ket administration during early adolescence displayed a reduced density of excitatory synapses on parvalbumin (PV) neurons persisting into adulthood. However, the synaptic development of excitatory pyramidal neurons was not affected by ketamine administration. Furthermore, the adult Ket group exhibited hyperexcitability and impaired socialization and working memory compared to the saline (Sal) administration group. These results strongly suggest that sub-chronic ketamine administration during adolescence results in functional deficits that persist into adulthood. Bioinformatic analysis indicated that the gene co-expression module1 (M1) decreased expression after ketamine exposure, which is crucial for synapse development in inhibitory neurons during adolescence. Collectively, these findings demonstrate that sub-chronic ketamine administration irreversibly impairs synaptic development, offering insights into potential new therapeutic strategies.