18F-FDG PET/CT findings of paratesticular alveolar rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) originates from primitive mesenchymal cells and is the most common soft tissue tumor in childhood. 18F-fluoro-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has been reported to be valuable in RMS staging and risk stratification. Paratesticular RMS is a relatively uncommon form of RMS, most of which are of the embryonal histologic type. Paratesticular alveolar RMS is associated with aggressive behavior, high metastatic potential, and poor outcomes. To the best of our knowledge, 18F-FDG PET/CT imaging findings of paratesticular alveolar RMS have never been described. Here, we report on a 16-year-old boy's rare paratesticular alveolar RMS with multiple metastases and its findings on 18F-FDG PET/CT. This case also demonstrates the potential value of 18F-FDG PET/CT in RMS staging and treatment decisions, and may aid in the differential diagnosis.

Protons intercalation induced hydrogen bond network in δ-MnO2 cathode for high-performance aqueous zinc-ion batteries.

Birnessite-type MnO2 (δ-MnO2) exhibits great potential as a cathode material for aqueous zinc-ion batteries (AZIBs). However, the structural instability and sluggish reaction kinetics restrict its further application. Herein, a unique protons intercalation strategy was utilized to simultaneously modify the interlayer environment and transition metal layers of δ-MnO2. The intercalated protons directly form strong O  H bonds with the adjacent oxygens, while the increased H2O molecules also establish a hydrogen bond network (O  H···O) between H2O molecules or bond with adjacent oxygens. Based on the Grotthuss mechanism, these bondings ultimately enhance the stability of layered structures and facilitate the rapid diffusion of protons. Moreover, the introduction of protons induces numerous oxygen vacancies, reduces steric hindrance, and accelerates ion transport kinetics. Consequently, the protons intercalated δ-MnO2 (H-MnO2-x) demonstrates exceptional specific capacity of 401.7 mAh/g at 0.1 A/g and a fast-charging performance over 1000 cycles. Density functional theory analysis confirms the improved electronic conductivity and reduced diffusion energy barrier. Most importantly, electrochemical quartz crystal microbalance tests combining with ex-situ characterizations verify the inhibitory effect of the interlayer proton environment on basic zinc sulfate formation. Protons intercalation behavior provides a promising avenue for the development of MnO2 as well as other cathodes in AZIBs.

Genome-wide identification, structural and gene expression analysis of BTB gene family in soybean.

BACKGROUND: The Bric-a-Brac/Tramtrack/Broad Complex (BTB) gene family plays essential roles in various biological processes in plants. These genes encode proteins that contain a conserved BTB domain, which is involved in protein-protein interactions and regulation of gene expression. However, there is no systematic reports on the BTB gene family in G.max. RESULTS: In total, 122 soybean BTB genes were identified, which were classified into four groups based on the phylogenetic analysis. Gene structures analysis indicated that the number of exon-intron in GmBTBs ranges from 0 to18. Cis-element analysis revealed that most GmBTB genes contained cis-elements related to an abiotic stress response. In addition, qRT-PCR analyses indicated that most GmBTBs are significantly up-regulated under salinity, drought, and nitrate stresses. They suggested their potential for targeted improvement of soybean response to multiple abiotic stresses and nitrate availability. CONCLUSION: These results provide valuable information for identifying the members of the GmBTB gene family in soybean and could provide a functional characterization of GmBTB genes in further research.

Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined. Methods: Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes. Results: In total, 27 canonical cancer gene mutations were identified, with TP53 the most frequently mutated gene, followed by KRAS. Interestingly, most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors, suggesting branching evolution in most PSC tumors. We identified two distinct molecular subtypes of PSC, driven primarily by immune infiltration and signaling. The Immune High (IM-H) subtype was associated with superior survival, highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs. Conclusions: We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

Lightweight cotton diseases real-time detection model for resource-constrained devices in natural environments.

Cotton, a vital textile raw material, is intricately linked to people's livelihoods. Throughout the cotton cultivation process, various diseases threaten cotton crops, significantly impacting both cotton quality and yield. Deep learning has emerged as a crucial tool for detecting these diseases. However, deep learning models with high accuracy often come with redundant parameters, making them challenging to deploy on resource-constrained devices. Existing detection models struggle to strike the right balance between accuracy and speed, limiting their utility in this context. This study introduces the CDDLite-YOLO model, an innovation based on the YOLOv8 model, designed for detecting cotton diseases in natural field conditions. The C2f-Faster module replaces the Bottleneck structure in the C2f module within the backbone network, using partial convolution. The neck network adopts Slim-neck structure by replacing the C2f module with the GSConv and VoVGSCSP modules, based on GSConv. In the head, we introduce the MPDIoU loss function, addressing limitations in existing loss functions. Additionally, we designed the PCDetect detection head, integrating the PCD module and replacing some CBS modules with PCDetect. Our experimental results demonstrate the effectiveness of the CDDLite-YOLO model, achieving a remarkable mean average precision (mAP) of 90.6%. With a mere 1.8M parameters, 3.6G FLOPS, and a rapid detection speed of 222.22 FPS, it outperforms other models, showcasing its superiority. It successfully strikes a harmonious balance between detection speed, accuracy, and model size, positioning it as a promising candidate for deployment on an embedded GPU chip without sacrificing performance. Our model serves as a pivotal technical advancement, facilitating timely cotton disease detection and providing valuable insights for the design of detection models for agricultural inspection robots and other resource-constrained agricultural devices.

Investigating gut microbiota-blood and urine metabolite correlations in early sepsis-induced acute kidney injury: insights from targeted KEGG analyses.

Background: The interplay between gut microbiota and metabolites in the early stages of sepsis-induced acute kidney injury (SA-AKI) is not yet clearly understood. This study explores the characteristics and interactions of gut microbiota, and blood and urinary metabolites in patients with SA-AKI. Methods: Utilizing a prospective observational approach, we conducted comparative analyses of gut microbiota and metabolites via metabolomics and metagenomics in individuals diagnosed with SA-AKI compared to those without AKI (NCT06197828). Pearson correlations were used to identify associations between microbiota, metabolites, and clinical indicators. The Comprehensive Antibiotic Resistance Database was employed to detect antibiotic resistance genes (ARGs), while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways informed on metabolic processes and microbial resistance patterns. Results: Our study included analysis of four patients with SA-AKI and five without AKI. Significant disparities in bacterial composition were observed, illustrated by diversity indices (Shannon index: 2.0 ± 0.4 vs. 1.4 ± 0.6, P = 0.230; Simpson index: 0.8 ± 0.1 vs. 0.6 ± 0.2, P = 0.494) between the SA-AKI group and the non-AKI group. N6, N6, N6-Trimethyl-L-lysine was detected in both blood and urine metabolites, and also showed significant correlations with specific gut microbiota (Campylobacter hominis and Bacteroides caccae, R > 0, P < 0.05). Both blood and urine metabolites were enriched in the lysine degradation pathway. We also identified the citrate cycle (TCA cycle) as a KEGG pathway enriched in sets of differentially expressed ARGs in the gut microbiota, which exhibits an association with lysine degradation. Conclusions: Significant differences in gut microbiota and metabolites were observed between the SA-AKI and non-AKI groups, uncovering potential biomarkers and metabolic changes linked to SA-AKI. The lysine degradation pathway may serve as a crucial link connecting gut microbiota and metabolites.

Remodelin delays non-small cell lung cancer progression by inhibiting NAT10 via the EMT pathway.

BACKGROUND: Lung cancer remains the foremost reason of cancer-related mortality, with invasion and metastasis profoundly influencing patient prognosis. N-acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)-acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non-small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. METHODS: We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT-PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK-8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient-derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. RESULTS: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E-cadherin level whereas decreased N-cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial-mesenchymal transition (EMT) pathway. CONCLUSIONS: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.

Effectiveness of the six-step approach guided online training program to improve knowledge of Mycoplasma pneumoniae pneumonia among pediatricians: a pretest-posttest study.

Background: In 2023, China witnessed an earlier and more widespread outbreak of Mycoplasma pneumoniae pneumonia (MPP). To address this situation, an online training program was designed to enhance the knowledge of MPP among pediatricians in Shanghai, China. Methods: An online training program on the diagnosis and treatment of MPP, guided by Kern's six-step approach, was developed by the Shanghai Pediatric Clinical Quality Control Center. A pre- and post-training survey was conducted using a 20-item self-administered questionnaire to investigate the pediatricians' knowledge of MPP. A linkage mechanism was established to match pretest/posttest questionnaires using personal identifiers. Paired t-tests and McNemar tests were performed to measure the differences, as appropriate, between pre- and post-training groups. A higher survey score indicated better knowledge. Results: There were 289 participants performed pre- and post-tests. The average age of the respondents was 38.7 years (standard deviation: 8.9). Over 80% of the participants were primary (32.5%) and intermediate (47.8%) pediatricians. Those from specialized hospitals accounted for the highest proportion (41.5%). The post-training group achieved significantly higher total scores than the pre-training group (91.3 vs. 67.7, t=22.48, P<0.001), regardless of the professional titles or hospital levels (all P<0.001). The accuracy rates of each question increased significantly in the post-training group (all P<0.001). Conclusions: The online training program effectively enhanced pediatricians' understanding of diagnosing and treating MPP. It is recommended to maintain continuous education and training targeting all healthcare providers.

Efficient and stable hybrid perovskite-organic light-emitting diodes with external quantum efficiency exceeding 40 per cent.

Light-emitting diodes (LEDs) based on perovskite semiconductor materials with tunable emission wavelength in visible light range as well as narrow linewidth are potential competitors among current light-emitting display technologies, but still suffer from severe instability driven by electric field. Here, we develop a stable, efficient and high-color purity hybrid LED with a tandem structure by combining the perovskite LED and the commercial organic LED technologies to accelerate the practical application of perovskites. Perovskite LED and organic LED with close photoluminescence peak are selected to maximize photon emission without photon reabsorption and to achieve the narrowed emission spectra. By designing an efficient interconnecting layer with p-type interface doping that provides good opto-electric coupling and reduces Joule heating, the resulting green emitting hybrid LED shows a narrow linewidth of around 30 nm, a peak luminance of over 176,000 cd m-2, a maximum external quantum efficiency of over 40%, and an operational half-lifetime of over 42,000 h.

Supramolecular assembly of isomeric SN-38 prodrugs regulated by conjugation sites.

Supramolecular polymers (SPs) are an emerging class of drug transporters employed to improve drug therapy. Through the rational design of self-assembling monomers, one can optimize the properties of the resulting supramolecular nanostructures, such as size, shape, surface chemistry, release, and, therefore, biological fates. This study highlights the design of isomeric SN38 prodrugs through the conjugation of hydrophilic oligo(ethylene glycol) (OEG) with hydroxyls at positions 10 and 20 on hydrophobic SN-38. Self-assembling prodrug (SAPD) isomers 10-OEG-SN38 and 20-OEG-SN38 can self-assemble into giant nanotubes and filamentous assemblies, respectively, via aromatic associations that dominate self-assembly. Our study reveales the influence of modification sites on the assembly behavior and ability of the SN38 SAPDs, as well as drug release and subsequent in vitro and in vivo antitumor effects. The SAPD modified at position 20 exhibits stronger π-π interactions among SN38 units, leading to more compact packing and enhanced assembly capability, whereas OEG at position 10 poses steric hindrance for aromatic associations. Importantly, owing to its higher chemical and supramolecular stability, 20-OEG-SN38 outperforms 10-OEG-SN38 and irinotecan, a clinically used prodrug of SN38, in a CT26 tumor model, demonstrating enhanced tumor growth inhibition and prolonged animal survival. This study presents a new strategy of using interactions among drug molecules as dominating features to create supramolecular assemblies. It also brings some insights into creating effective supramolecular drug assemblies via the engineering of self-assembling building blocks, which could contribute to the optimization of design principles for supramolecular drug delivery systems.

A method for extracting corneal reflection images from multiple eye images.

The incident light reflected from the cornea is rich in information about the human surroundings, and these reflected rays are imaged by the camera, which can be used for research on human consciousness and gaze analysis, and produce certain help in the fields of psychology, human computer interaction and disease diagnosis. However, limited by the low corneal reflection ability, when a high-definition camera captures corneal reflecting rays, a large amount of color and texture interference from the iris can seriously contaminate the corneal reflection images, resulting in low usability and ubiquity of corneal reflection images. In this paper, we propose a corneal reflection image extraction method with multiple eye images as input. We align the iris regions of multiple eye images with the help of iris localization method, and by comparing multiple iris regions, we obtain the complementary iris regions, so that the iris interference in the corneal reflection region can be stripped completely. A large number of experiments have demonstrated that our work can effectively mitigate iris interference and effectively improve the quality of corneal reflection images.

Quantitative profiling of m6A at single base resolution across the life cycle of rice and Arabidopsis.

N6-methyladenosine (m6A) plays critical roles in regulating mRNA metabolism. However, comprehensive m6A methylomes in different plant tissues with single-base precision have yet to be reported. Here, we present transcriptome-wide m6A maps at single-base resolution in different tissues of rice and Arabidopsis using m6A-SAC-seq. Our analysis uncovers a total of 205,691 m6A sites distributed across 22,574 genes in rice, and 188,282 m6A sites across 19,984 genes in Arabidopsis. The evolutionarily conserved m6A sites in rice and Arabidopsis ortholog gene pairs are involved in controlling tissue development, photosynthesis and stress response. We observe an overall mRNA stabilization effect by 3' UTR m6A sites in certain plant tissues. Like in mammals, a positive correlation between the m6A level and the length of internal exons is also observed in plant mRNA, except for the last exon. Our data suggest an active m6A deposition process occurring near the stop codon in plant mRNA. In addition, the MTA-installed plant mRNA m6A sites correlate with both translation promotion and translation suppression, depicting a more complicated regulatory picture. Our results therefore provide in-depth resources for relating single-base resolution m6A sites with functions in plants and uncover a suppression-activation model controlling m6A biogenesis across species.

Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into "ARness".

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.

Enabling Quasi-Zero-Strain Behavior of Layered Oxide Cathodes via Multiple-cations Induced Order-to-Disorder Transition.

The chemically pre-intercalated lattice engineering is widely applied to elevate the electronic conductivity, expand the interlayer spacing, and improve the structural stability of layered oxide cathodes. However, the mainstream unitary metal ion pre-intercalation generally produces the cation/vacancy ordered superstructure, which astricts the further improvement of lattice respiration and charge-carrier ion storage and diffusion. Herein, a multiple metal ions pre-intercalation lattice engineering is proposed to break the cation/vacancy ordered superstructure. Taking the bilayer V2O5 as an example, Ni, Co, and Zn ternary ions are simultaneously pre-intercalated into its interlayer space (NiCoZnVO). It is revealed that the Ni─Co neighboring characteristic caused by Ni(3d)-O(2p)-Co(3d) orbital coupling and the Co-Zn/Ni-Zn repulsion effect due to chemical bond incompatibility, endow the NiCoZnVO sample with the cation/vacancy disordered structure. This not only reduces the Li+ diffusion barrier, but also increases the diffusion dimension of Li+ (from one-dimension to two-dimension). Particularly, Ni, Co, and Zn ions co-pre-intercalation causes a prestress, which realizes a quasi-zero-strain structure at high-voltage window upon charging/discharging process. The functions of Ni ion stabilizing the lattice structure and Co or Zn ions activating more Li+ reversible storage reaction of V5+/V4+ are further revealed. The cation/vacancy disordered structure significantly enhances Li+ storage properties of NiCoZnVO cathode.

Enantioselective Synthesis of the Active Sex Pheromone Components of the Female Lichen Moth, Lyclene dharma dharma, and Their Enantiomers.

The Lichen moth, Lyclene dharma dharma (Arctiidae, Lithosiinae), plays a significant role in forest ecosystem dynamics. A concise and novel method to synthesize the active sex pheromone components, (S)-14-methyloctadecan-2-one ((S)-1), (S)-6-methyloctadecan-2-one ((S)-2), and their enantiomers has been developed. Key steps in the synthesis include the use of Evans' chiral auxiliaries, Grignard cross-coupling reactions, hydroboration-oxidation, and Wacker oxidation. The synthesized sex pheromone components hold potential value for studies on communication mechanisms, species identification, and ecological management.

A self-healing thermogelling polymer with tunable transparency based on biomolecule alginate grafting phenylboronic acid.

Thermogelling polymers with transparency, structure stability and biocompatibility are promising for biomedicine application. In this study, a thermogelling polymer P-C5PEG with tunable transparency was developed by the reaction between alternating copolymer C5PEG and chemically modified biomolecule Alg-PBA via boronic ester bonds. The sol-to-gel transition of P-C5PEG aqueous solution sensitively responded to changes in temperature, and the critical value could be adjusted between 15 and 40 °C by varying the content of C5PEG and Alg-PBA. As the weight ratio of Alg-PBA to C5PEG was over 0.3, the transparency of as-synthesized hydrogel kept above 75 % at 37 °C. Meanwhile, immersion P-C5PEG hydrogel in CaCl2 solution significantly increased its mechanical strength by 3 times due to chelation effect. The shear-resistance and self-healing properties were ensured by dynamic boronic ester bonds due to the protective effect of hydrophobic gel network. As a drug delivery, P-C5PEG hydrogel had a swelling rate of 3748.7 ± 103 % in PBS and could continuously release fluorescein sodium within 24 h. Moreover, the in vitro degradability and cytotoxicity of P-C5PEG was confirmed. Finally, the mechanisms behind the thermogelling property and tunable transparency were revealed. Overall, this thermogelling P-C5PEG polymer, with tunable transparency and thermo-responsiveness, exhibits great potential for biomedicine application.

Clonal evolution of hematopoietic stem cells after cancer chemotherapy.

Normal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the development of myeloid malignancies 1 . The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal HSPCs is not well defined. We conducted whole-genome sequencing on 1,032 single-cell-derived HSPC colonies from 10 patients with multiple myeloma (MM), who had undergone various chemotherapy regimens. Our findings reveal that melphalan treatment distinctly increases mutational burden with a unique mutation signature, whereas other MM chemotherapies do not significantly affect the normal mutation rate of HSPCs. Among these therapy-induced mutations were several oncogenic drivers such as TET2 and PPM1D . Phylogenetic analysis showed a clonal architecture in post-treatment HSPCs characterized by extensive convergent evolution of mutations in genes such as TP53 and PPM1D . Consequently, the clonal diversity and structure of post-treatment HSPCs mirror those observed in normal elderly individuals, suggesting an accelerated clonal aging due to chemotherapy. Furthermore, analysis of matched therapy-related myeloid neoplasm (t-MN) samples, which occurred 1-8 years later, enabled us to trace the clonal origin of t-MNs to a single HSPC clone among a group of clones with competing malignant potential, indicating the critical role of secondary mutations in dictating clonal dominance and malignant transformation. Our findings suggest that cancer chemotherapy promotes an oligoclonal architecture with multiple HSPC clones possessing competing leukemic potentials, setting the stage for the selective emergence of a singular clone that evolves into t-MNs after acquiring secondary mutations. These results underscore the importance of further systematic research to elucidate the long-term hematological consequences of cancer chemotherapy.

Electron Spin Broken-Symmetry of Fe-Co Diatomic Pairs to Promote Kinetics of Bifunctional Oxygen Electrocatalysis for Zinc-Air Batteries.

Designing bifunctional catalysts to reduce the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) reaction barriers while accelerating the reaction kinetics is perceived to be a promising strategy to improve the performance of Zinc-air batteries. Unsymmetric configuration in single-atom catalysts has attracted attention due to its unique advantages in regulating electron orbitals. In this work, a seesaw effect in unsymmetric Fe-Co bimetallic monoatomic configurations is proposed, which can effectively improve the OER/ORR bifunctional activity of the catalyst. Compared with the symmetrical model of Fe-Co, a strong charge polarization between Co and Fe atoms in the unsymmetric model is detected, in whom the spin-down electrons around Co atoms are much higher than those spin-up electrons. The seesaw effect occurred between Co atoms and Fe atoms, resulting in a negative shift of the d-band center, which means that the adsorption of oxygen intermediates is weakened and more conducive to their dissociation. The optimized reaction kinetics of the catalyst leads to excellent performance in ZABs, with a peak power density of 215 mW cm-2 and stable cycling for >1300 h and >4000 cycles. Flexible Zinc-air batteries have also gained excellent performance to demonstrate their potential in the field of flexible wearables.

ROCK Inhibitor Fasudil Attenuates Neuroinflammation and Associated Metabolic Dysregulation in the Tau Transgenic Mouse Model of Alzheimer's Disease.

The pathological manifestations of Alzheimer's disease (AD) include not only brain amyloid ß protein (Aß) containing neuritic plaques and hyperphosphorylated tau (p-tau) containing neurofibrillary tangles but also microgliosis, astrocytosis, and neurodegeneration mediated by metabolic dysregulation and neuroinflammation. METHOD: While antibody-based therapies targeting Aß have shown clinical promise, effective therapies targeting metabolism, neuroinflammation, and p-tau are still an urgent need. Based on the observation that Ras homolog (Rho)-associated kinases (ROCK) activities are elevated in AD, ROCK inhibitors have been explored as therapies in AD models. This study determines the effects of fasudil, a ROCK inhibitor, on neuroinflammation and metabolic regulation in the P301S tau transgenic mouse line PS19 that models neurodegenerative tauopathy and AD. Using daily intraperitoneal (i.p.) delivery of fasudil in PS19 mice, we observed a significant hippocampal-specific decrease of the levels of phosphorylated tau (pTau Ser202/Thr205), a decrease of GFAP+ cells and glycolytic enzyme Pkm1 in broad regions of the brain, and a decrease in mitochondrial complex IV subunit I in the striatum and thalamic regions. RESULTS: Although no overt detrimental phenotype was observed, mice dosed with 100 mg/kg/day for 2 weeks exhibited significantly decreased mitochondrial outer membrane and electron transport chain (ETC) protein abundance, as well as ETC activities. CONCLUSION: Our results provide insights into dose-dependent neuroinflammatory and metabolic responses to fasudil and support further refinement of ROCK inhibitors for the treatment of AD.

Recreational gymnastics exercise of moderate intensity enhances executive function in Chinese preschoolers: A randomized controlled trial.

The current study aimed to investigate the impact of recreational gymnastics on executive function in Chinese preschoolers, with a focus on gymnastics potential to enhance core components of executive function. A total of 63 preschool children who received full-time education were randomly assigned to either an intervention group (N = 31, mean age = 66.27 months, SD = 3.12 months) or a control group (N = 32, mean age = 66.79 months, SD = 3.34 months). The intervention group engaged in recreational gymnastics for 60 min, three times a week for 12 weeks. Meanwhile, the control group continued with their typical outdoor activities at kindergarten and did not participate in any organized sports. The intervention program was primarily conducted through group play and was facilitated by teachers who underwent standardized training. Various simple and complex tasks were utilized to evaluate delay gratification (Snack delay and Wrapped gift), inhibitory control (Stop signal task and Circle drawing task), working memory (Letter memory task and Keep track task), and cognitive flexibility (Go/No-Go task and Dots task). The analysis of covariance revealed that the children who participated in the intervention outperformed the control group on most simple and complex executive function tasks. Specifically, these children demonstrated an enhanced ability to regulate persistent responses, process and update information, and manage high cognitive conflict. The findings of this investigation lend support to the hypothesis that moderate-intensity recreational gymnastics is an efficacious means of enhancing executive function in early childhood. Future research should employ a larger sample size, incorporate a long-term follow-up design, and utilize a multi-method approach to further substantiate the impact of moderate-intensity gymnastics on the executive function of young children, as well as to investigate its underlying mechanism and generalizability.