Formation Of Fragments Research Articles

TPR is required for cytoplasmic chromatin fragment formation during senescence.

During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme - the senescence associated secretory phenotype (SASP) - driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear. Here we show that TPR, a protein of the nuclear pore complex basket required for heterochromatin re-organisation during senescence, is also required for the very early activation of NF-κB signalling during the stress-response phase of oncogene-induced senescence. This is prior to activation of the SASP and occurs without affecting NF-κB nuclear import. We show that TPR is required for the activation of innate immune signalling at these early stages of senescence and we link this to the formation of heterochromatin-enriched cytoplasmic chromatin fragments thought to bleb off from the nuclear periphery. We show that HMGA1 is also required for cytoplasmic chromatin fragment formation. Together these data suggest that re-organisation of heterochromatin is involved in altered structural integrity of the nuclear periphery during senescence, and that this can lead to activation of cytoplasmic nucleic acid sensing, NF-κB signalling, and activation of the SASP.

Rapid Identification of Chemical Constituents in New Compound Aloe Capsule Based on UPLC-Q-Orbitrap-MS.

The chemical composition of the new compound aloe capsule (NCAC) has not been fully elucidated to date, which poses challenges for pharmacology, scientific, and rational drug use. In this study, a rapid and sensitive method was established to comprehensively study the constituents in the NCAC. The contents of the NCAC were analyzed by UPLC-Q-Orbitrap-MS and data postprocessing technology. Firstly, the extract was separated by UPLC system, and the fragment information was obtained under positive and negative ions and then compared with the characteristic fragments described in the literature, so as to achieve the purpose of rapid identification of the compound of NCAC. A total of 56 compounds including 21 chromones, 6 pyranones, 7 anthraquinones, 7 anthrone, 5 alkaloids, 4 amino acids, and 6 other components were detected in NCAC by comparing the retention time and mass spectrometry information and retrieving the reference literature. The UPLC-Q-Orbitrap-MS method was developed and utilized successfully to identify the major constituents in NCAC and would be helpful for improving the quality control standard of NCAC.

Predicting Tandem Mass Spectra of Small Molecules Using Graph Embedding of Precursor-Product Ion Pair Graph.

Liquid chromatography-mass spectrometry (LC-MS)-based metabolomics identification relies heavily on high-quality MS/MS data; MS/MS prediction is a good way to address this issue. However, the accuracy of the prediction, resolution, and correlation with chemical structures have not been well-solved. In this study, we have developed a MS/MS prediction method, PPGB-MS2, which transforms the MS/MS prediction into fragment intensity prediction, and the concept of precursor-product ion pair graph bags (PPGBs) was introduced to represent fragments, achieving uniform representation of precursor and product ion structures and MS/MS fragmentation information. The chemical structure information is kept before it is incorporated into machine learning models. Due to the PPGB representation, graph neural networks (GNNs) can be utilized to achieve MS/MS fragment intensity prediction. The system was trained and evaluated using [M+H]+ and [M-H]- data acquired by an Agilent QTOF 6530 in the NIST 20 tandem MS database. Results demonstrated that the average cosine similarity is 0.71 in the test set, which is higher than classical MS/MS prediction methods. PPGB-MS2 also achieves high-resolution MS/MS prediction due to its effective management of the correspondence between fragments and structures.

X-ray-Induced Molecular Catapult: Ultrafast Dynamics Driven by Lightweight Linkages.

In our work, we demonstrate that X-ray photons can initiate a "molecular catapult" effect, leading to the dissociation of chemical bonds and the formation of heavy fragments within just a few femtoseconds. We reconstruct the momenta of fragments from a three-body dissociation in bromochloromethane using the ion pair average (IPA) reference frame, demonstrating how light atomic groups, such as alkylene and alkanylene, can govern nuclear dynamics during the dissociation process, akin to projectiles released by a catapult. Supported by ab initio calculations, this work highlights the crucial role of low-reduced-mass vibrational modes in driving ultrafast chemical processes.

Influence of the RF-power on the etching yields and surface morphology in reactive ion beam etching of Si and photoresist

The change in ion energy distribution and composition of a reactive ion beam produced by an RF-excited ion beam source and operation with a mixture of CHF3 and O2 was investigated and correlated with the etching behavior. To this end, measurements were performed with an energy-selective mass spectrometer to determine ion energy distributions, current density measurements for the measurement of current density distributions of the ion beam, and tactile measurements to determine the etching rates of Si and photoresist. The morphology of the photoresist was measured with a scanning force microscope. In particular, alterations in the etching yield and surface morphology of the photoresist can be observed in response to changes in the applied RF-power. An increase in plasma density leads to an increase in fragmentation processes of the injected reactive gases, resulting in the formation of smaller fragments. These smaller fragments have a chemical impact on the substrate surface, which affects the etching performance. These effects can have significant consequences in the context of long-time reactive ion beam processing for patterning applications.

Developing a Knowledge-Based Online Recommendation System to Guide STD Patients Through Their Journey

Sexually transmitted diseases (STDs) significantly impact public health, affecting one in five U.S. adults and imposing substantial economic burdens. Many at-risk individuals seek information and support online rather than through regular testing, facing challenges due to fragmented information and a lack of personalized recommendations. This study develops an online health recommendation system (OHRS) tailored for STD patients, integrating informational and emotional support based on their disease journey. Using a BERT-based named entity recognition (NER) algorithm, the system identifies patient emotions and stages from online posts, providing relevant support resources. Data collection for designing a recommendation engine included analyzing online posts and consulting healthcare experts. The system's effectiveness was validated through user-based simulation studies. Key contributions include developing text-mining algorithms, creating a knowledge-based recommendation system, and proposing design principles for AI-driven support systems for stigmatized conditions.

MuSE: A deep learning model based on multi-feature fusion for super-enhancer prediction

Although bioinformatics-based methods accurately identify SEs (Super-enhancers), the results depend on feature design. It is foundational to representing biological sequences and automatically extracting their key features for improving SE identification. We propose a deep learning model MuSE (Multi-Feature Fusion for Super-Enhancer), based on multi-feature fusion. This model utilizes two encoding methods, one-hot and DNA2Vec, to signify DNA sequences. Specifically, one-hot encoding reflects single nucleotide information, while k-mer representations based on DNA2Vec capture both local sequence fragment information and global sequence characteristics. These types of feature vectors are conducted and combined by neural networks, which aim at SE prediction. To validate the effectiveness of MuSE, we design extensive experiments on human and mouse species datasets. Compared to baselines such as SENet, MuSE improves the prediction of F1 score to a maximum improvement exceeding 0.05 on mouse species. The k-mer representations based on DNA2Vec among the given features have the most important impact on predictions. This feature effectively captures context semantic knowledge and positional information of DNA sequences. However, its representation of the individuality of each species negatively affects MuSE's generalization ability. Nevertheless, the cross-species prediction results of MuSE improve again to reach an AUC of nearly 0.8, after removing this type of feature. Source codes are available at https://github.com/15831959673/MuSE.

Voices From the Frontline: A Reflexive Thematic Analysis Illuminating Perioperative Practice Realities in Southern Ethiopian Teaching Hospitals.

Despite national efforts, gaps persist in Ethiopian perioperative care. This reflexive thematic analysis aimed to investigate the contextual challenges faced in delivering perioperative care. In-depth interviews were conducted with 20 healthcare professionals, including anesthetists, nurses, and surgeons, to gain a frontline perspective of perioperative practice realities. The analysis revealed eight interconnected themes: systemic infrastructure vulnerabilities, workforce expansion uncertainties, workforce demoralization, fragile perioperative safety culture, hierarchical structures and communication barriers, financial barriers to care, fragmented information systems, and fragile governance with sociopolitical instability. Local deficiencies in resources and equipment were amplified by global challenges, creating a precarious care environment. While workforce numbers increased, concerns persisted about competency and training quality. Systemic pressures and unmet professional needs contributed to staff demoralization. Inconsistent safety practices and top-down quality improvement initiatives hindered sustainable progress. Rigid hierarchies and departmental silos impeded effective teamwork and resource coordination. Financial constraints created significant barriers to care access and ethical dilemmas for providers. Incomplete digitalization and inconsistent documentation practices compromised continuity of care and data-driven improvements. Overarching sociopolitical instability and weak governance cascaded into healthcare system disruptions. The findings underscore the need for a multifaceted approach to strengthen perioperative care, including improving infrastructure, enhancing workforce development, fostering a culture of safety, breaking down hierarchical barriers, addressing financial accessibility, implementing robust information systems, and building resilient governance structures amidst adversity.

Human CFTR deficient iPSC-macrophages reveal impaired functional and transcriptomic response upon Pseudomonas aeruginosa infection.

Cystic fibrosis (CF) is a hereditary autosomal recessive disease driven by deleterious variants of the CFTR gene, leading, among other symptoms, to increased lung infection susceptibility. Mucus accumulation in the CF lung is, as of yet, considered as one important factor contributing to its colonization by opportunistic pathogens such as Pseudomonas aeruginosa. However, in recent years evidence was provided that alveolar macrophages, which form the first line of defense against airborne pathogens, seem to be intrinsically defective with regard to bactericidal functionality in the CF lung. To assess the impact of CFTR deficiency in human macrophages only insufficient systems are available. To address this problem and to evaluate the role of CFTR in human macrophages, we successfully differentiated human induced pluripotent stem cells (iPSC) from a CF p.Phe508del homozygous individual and a healthy donor into primitive macrophages (iMacΔF508 and iMacWT), respectively, and compared the bactericidal functionality in the relevant cell type. iMacΔF508 showed impaired P. aeruginosa clearance and intracellular killing capacity in comparison to iMacWT. Furthermore, iMacΔF508 exhibited a less acidic lysosomal pH, and upon P. aeruginosa infection, there were signs of mitochondrial fragmentation and autophagosome formation together with a hyperinflammatory phenotype and deficient type I interferon response. In summary, we present a defective phenotype in iMacΔF508 upon P. aeruginosa infection, which will constitute an ideal platform to further study the role of macrophages in the context of CF.

Examining Macro-Level Barriers and Facilitators to Scaling Up Integrated Care from a Complexity Perspective: A Multi-Case Study of Cambodia, Slovenia, and Belgium.

The 'Scale-Up diaBetes and hYpertension care' (SCUBY) project provides evidence on scaling-up integrated care (IC) in Cambodia, Slovenia, and Belgium. This paper examines macro-level barriers and facilitators to scaling up IC in these settings. We used a multi-case study design, with each country being a case. Document review, focus groups, and stakeholder interviews were conducted. The WHO health system building blocks guided the thematic analysis. We then visualised and examined the interlinkages between barriers in each country. Common challenges to scaling up IC across the three health systems relate to: governance and leadership; health workforce; inadequate health financing system; and fragmented health information systems. In Cambodia, access to non-communicable disease (NCD) services and medicine are important issues. IC scale-up is facilitated by its strong governance and public health service model in Slovenia but health workforce shortages risk progress. In Belgium, the fragmented governance system and predominant fee-for-service provider payment are important barriers. A common response to health workforce and workload challenges was task shifting: to primary care nurses in Belgium, peer supporters in Slovenia, and community health workers in Cambodia. Examining differences and similarities between barriers in each health system stimulated reciprocal learning. Interactions between health system barriers in specific contexts require further attention to move complex health systems forward.

A new Rose Bengal glycopolymer: Photosensitization in two stages

Antimicrobial photodynamic therapy is a promising alternative to deal with antimicrobial resistance. However, both the low specificity and low local oxygen molecular concentrations decrease the antimicrobial efficiency limiting its use. An interesting approach to the problem is the use of molecules that can react reversibly with singlet oxygen by the formation of reversible endoperoxides, such as naphthalene, anthracene and pyridone derivatives. Particularly, the use of these molecules with mannosyl derivatives allow the interaction with adhesins presented on pili and fimbriae improving the localization near to bacteria. In this work, we synthesized polymeric nanoparticles able to generate singlet oxygen (under both irradiation and dark conditions) in the vicinity of a center capable of recognizing mannose and oxidize nearby biomolecules. Rose Bengal was used as photosensitizer due to its attractive photophysical properties (vis absorption, high singlet oxygen generation) and biocompatibility. The polymeric nanoparticles were obtained by radical polymerization using polyvinyl alcohol as a template, showing sizes around 300 nm with negative zeta potential by dynamic light scattering. The singlet oxygen generation was monitored following DPBF consumption and showed to be dependent on the amount of pyridone in the feed of polymers. In addition, the release of singlet oxygen was also dependent on pyridone concentration showing a slower rate constant at 40 % pyridone, while for contents of 10 % and 60 % higher rate constants were observed. The specific interaction of glycopolymers with Concanavalin A was demonstrated by successful agglutination assays, but also a low participation of unspecific interactions for polymers without mannosyl derivatives was observed. On the other hand, the oxidation of amino acids of Concanavalin A was monitored by acrylamide gel electrophoresis. Type I and Type II photosensitization were observed with the formation of dimers and fragments with lower molecular weight, while in dark conditions only products with lower molecular weight were observed, result consistent with singlet oxygen released by pyridone endoperoxides.

The importance of legal reserves in the conservation of the Dark-winged Trumpeter, Psophia obscura (Aves − Psophiidae), given climate change in the eastern Amazon

In recent decades, the Amazon rainforest has faced intense forest cover loss, compromising the environmental balance and negatively affecting local biodiversity. Along with these anthropogenic impacts, there are also the effects associated with climate change, which has intensified every year, causing severe droughts.Consequently, the formation of forest fragments is among the main factors of biodiversity loss, leading to a reduction of the species ’ living area, interrupting the gene flow between populations, and facilitating the occurrence of forest fires and hunting. One of the main measures to combat these impacts and their effects is the creation of protected areas by the governments of each country. In Brazil, environmental legislation requires all rural properties to protect a designated percentage of the region’s natural vegetation and that these areas, referred to as legal reserves, cannot be used or modified. However, there is still little information on these legal reserves’ effectiveness regarding their role in maintaining local biodiversity and their complementary function to the country’s official system of Protected Areas. In this sense, as a way to evaluate the effects of anthropogenic impacts on Amazonian biodiversity and the role of legal reserves in the face of predicted climate change, we evaluate how these reserves can contribute to the maintenance of a critically endangered bird species of the Amazon, the Dark-winged Trumpeter (Psophia obscura). This species is restricted to the “Belem Endemism Area (BEA),” located in the extreme east of the Brazilian Amazon. For this, we generated climate suitability models of the target taxon for the present and future pessimistic (SSP5-8.5) and optimistic (SSP2-4.5) scenarios for the year 2100. We obtained 27 unique occurrences of P. obscura within the BEA area. We then compared the area climatically suitable for the occurrence of this bird for the current and future emission scenarios, taking into account the availability of areas in the Legal Reserves within the BEA. Thus, we projected two alternative future scenarios: the first being optimistic with and without mitigation (Fut 4.5 of the implemented Legal Reserves − ILR and Fut 4.5 total legal reserves − RLT), and the second pessimistic with and without mitigation (Fut 8.5 of the ILR and Fut 8.5 TLR). Our results show that the legal reserves currently implemented are not fulfilling their role in conserving P. obscura. However, implementing the TLR that makes up the future scenario with mitigation can reverse this situation.

Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system

Huntington's Disease (HD) is a neurodegenerative disorder, part of the nine identified inherited polyglutamine (polyQ) diseases. Most commonly, HD pathophysiology manifests in middle-aged adults with symptoms including progressive loss of motor control, cognitive decline, and psychiatric disturbances. Associated with the pathophysiology of HD is the formation of insoluble fragments of the huntingtin protein (htt) that tend to aggregate in the nucleus and cytoplasm of neurons. To track both the intracellular progression of the aggregation phenotype as well as the physiological deficits associated with mutant htt, two constructs of human HTT were expressed in the Drosophila melanogaster nervous system with varying polyQ lengths, non-pathogenic-htt (NP-htt) and pathogenic-htt (P-htt), with an N-terminal RFP tag for in vivo visualization. P-htt aggregates accumulate in the ventral nerve cord cell bodies as early as 24 h post hatching and significant aggregates form in the segmental nerve branches at 48 h post hatching. Organelle trafficking up- and downstream of aggregates formed in motor neurons showed severe deficits in trafficking dynamics. To explore putative downstream deficits of htt aggregation, ultrastructural changes of presynaptic motor neurons and muscles were assessed, but no significant effects were observed. However, the force and kinetics of muscle contractions were severely affected in P-htt animals, reminiscent of human chorea. Reduced muscle force production translated to altered locomotory behavior. A novel HD aggregation model was established to track htt aggregation throughout adulthood in the wing, showing similar aggregation patterns with larvae. Expressing P-htt in the adult nervous system resulted in significantly reduced lifespan, which could be partially rescued by feeding flies the mTOR inhibitor rapamycin. These findings advance our understanding of htt aggregate progression as well the downstream physiological impacts on the nervous system and peripheral tissues.

RELIGIOUS MODERATION, EXPERT, SOCIAL MEDIA CONTENT NEWBIE? RELIGIOUS EXTENSION OFFICERS IN SOCIAL MEDIA

About sixty-seven thousand religious extension officers (Penyuluh Agama), representing six religions in the state service, are on the frontline of the massive campaign of religious moderation organized by the Ministry of Religious Affairs. They are the sole body with religious competence dealing with the increasing religious conservatism, radicalism, and extremism. The study observes the digital performance and agency of Penyuluh in social media. It describes the complexity of their position within the challenge of religious extremism, the execution of a religious moderation campaign, and social media engagement. Data collection utilizes mixed methods, while the analysis employs netnographic and descriptive-inductive methods. The findings demonstrate the digital divide context, the tendency of Penyuluh to reproduce the structure, hence limiting their agency, limited digital mastery and digital literacy of many of Penyuluh, fragmented institutional information system, and the vulnerability of instant messenger engagement that is prone to epistemic bubble and echo chamber effects.

Modeling interactions between hydraulic fracture and pre-existing microcracks in crystalline rocks using hydro-grain-texture model

The heterogeneity of the mineral grains and pre-existing microcracks significantly impacts the cracking behavior of crystalline rocks. However, these characteristics have not been adequately addressed in the existing hydraulic fracturing studies. To bridge this gap, this study introduces a fluid-solid coupling method enhanced by a microcrack simulation component, called Hydro-Grain-Texture Model (HGTM), to investigate the influence of mineral structures and pre-existing microcracks on hydraulic fracturing processes in granite. Compared with existing methods, the HGTM incorporates a “grain growth” algorithm that can more accurately represent the characteristics of mineral grains. This study investigates the base case of intact rock, and four additional cases featuring microcracks oriented in various directions, i.e., horizontal, diagonal, vertical and complex microcracks, under both hydrostatic and non-hydrostatic in-situ stress conditions. The HGTM effectively captures a range of microscopic behaviors during the hydraulic fracturing of granite, including the formation of rock fragments, fracture branches, and dry fractures, among others. Furthermore, by comparing numerical results for breakdown pressure with analytical results, the accuracy of the HGTM in predicting breakdown pressure is substantiated. The findings indicate that mineral structures (grain boundaries) and microcracks contribute to a more intricate pattern of hydraulic fractures propagation. The pre-existing microcracks significantly influence the propagation path of primary hydraulic fractures. Under fluid-driven pressures, these pre-existing microcracks experience shear failure distinct from tensile failure observed in the surrounding rock matrix.

Prenatal Opioid and Alcohol Exposures: Association with Altered Placental Serotonin Transporter Structure and/or Expression.

Fetal exposures to many drugs of abuse, e.g., opioids and alcohol (EtOH), are associated with adverse neurodevelopmental problems in early childhood, including abnormalities in activity of the serotonin (5HT) transporter (SERT), which transports 5HT across the placenta. Little is known about the effects of these drugs on SERT expression. Pregnant women who used EtOH or opioids were compared to gestational age-matched controls using a structured questionnaire to determine prenatal substance exposure. Following elective pregnancy termination, placental membranous vesicles and exosomes were prepared from first and second trimester human placentas. Changes in EtOH- or opioid-exposed placental SERT expression and modifications were assessed by quantitative western blot. Novel SERT isoforms were sequenced and analyzed. Opioid-exposed but not EtOH-exposed maternal placentas showed SERT cleavage and formation of new SERT fragments (isoforms). Alcohol-exposed cases showed reduced SERT levels. Antibodies to the N-terminal SERT region did not recognize either of the two cleavage products, while antibodies to the central and C-terminal regions recognized both bands. The secondary band seen in the opioid group may represent a hypophosphorylated SERT fragment. These changes in SERT modifications and expression may result in altered fetal brain serotonergic neurotransmission, which could have neurodevelopmental implications.

An automatic LC-MS/MS data analysis workflow for herbal compound annotation with AutoAnnotatoR: A case study of ten botanical origins of Fritillaria species

BackgroundDespite the widespread implementation of analytical hardware capable of recording large-scale datasets for botanical natural products, the data processing procedures for compound annotation remain a bothersome obstacle that demand a tremendous amount of time and expert knowledge. MethodsHerein, an automatic LC-MS/MS data analysis workflow with AutoAnnotatoR was introduced for the compound annotation of plant derived natural products, which has the merits of great efficiency, high accuracy, saving time and simplified process. This procedure enabled automatic matching of MS2 data with characteristic fragment ions, as well as MS1 data with compound libraries, which improves the accuracy of structural elucidation. Notably, the optimization of collision energy for each target ion was successfully performed for the first time, facilitating the acquisition of comprehensive fragmentation information. ResultsThe automatic analysis workflow with AutoAnnotatoR was successfully applied for the annotation of alkaloids from 10 botanical origins of Fritillaria species. Consequently, a total of 2684 chemical constituents were tentatively characterized, with 23 components being unambiguously validated by reference standards and 2434 being probable novel chemicals. ConclusionThe entire data analysis procedure takes only a few hours, vastly improving analysis speed while assuring high accuracy. This method provides a powerful tool for the rapid and precise annotation of complex natural products. The workflow is publicly accessible on Github as an open-source R package called AutoAnnotatoR (https://github.com/anyaling2022/AutoAnnotatoR).

Pan-Draft: automated reconstruction of species-representative metabolic models from multiple genomes

The accurate reconstruction of genome-scale metabolic models (GEMs) for unculturable species poses challenges due to the incomplete and fragmented genetic information typical of metagenome-assembled genomes (MAGs). While existing tools leverage sequence homology from single genomes, this study introduces pan-Draft, a pan-reactome-based approach exploiting recurrent genetic evidence to determine the solid core structure of species-level GEMs. By comparing MAGs clustered at the species-level, pan-Draft addresses the issues due to the incompleteness and contamination of individual genomes, providing high-quality draft models and an accessory reactions catalog supporting the gapfilling step. This approach will improve our comprehension of metabolic functions of uncultured species.

Quantum Chemical Analysis of the Molecular and Fragment Ion Formation of Butyrophenone by High-Electric Field Tunnel Ionization at Atmospheric Pressure.

The molecular ion M+· was observed when the liquid sample of butyrophenone was supplied using atmospheric pressure corona discharge (APCD). In contrast, the vapor supply resulted in the formation of the protonated molecule [M+H]+. The mass spectrum obtained with the liquid supply showed two distinctive fragment ions at m/z 105 and 120, resulting from α-cleavage and McLafferty rearrangement (McLR), respectively. The APCD spectrum showed peaks of M+· and the characteristic two fragment ions that were the same as the field ionization mass spectra of butyrophenone as reported by Chait et al. and Beckey et al. The formation of the molecular and fragment ions strongly indicated that high-electric field tunnel ionization (HEFTI) occurs by the HEF strength exceeding 108 V/m at the tip of the corona needle in APCD. The charge and spin density distributions of the molecular and fragment ions were analyzed by quantum chemical calculations using time-dependent density functional theory (TDDFT) and natural bond orbital (NBO) analysis.

PFKFB3 ameliorates ischemia-induced neuronal damage by reducing reactive oxygen species and inhibiting nuclear translocation of Cdk5.

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) plays an essential role in glycolysis and in the antioxidant pathway associated with glutathione. Therefore, we investigated the effects of PFKFB3 on oxidative and ischemic damage. We synthesized a fusion protein of transactivator of transcription (Tat)-PFKFB3 to facilitate its passage into the intracellular space and examine its effects against oxidative stress induced by hydrogen peroxide (H2O2) treatment and ischemic damage caused by occlusion of the common carotid arteries for 5min in gerbils. The Tat-PFKFB3 protein was efficiently delivered into HT22 cells in a concentration- and time-dependent manner, with higher levels observed 18h after treatment. Furthermore, treatment with 6 µM Tat-PFKFB3 demonstrated intracellular delivery into HT22 cells, as analyzed through immunocytochemical staining. Moreover, it significantly ameliorated the reduction of cell viability induced by 200 µM H2O2 treatment. Tat-PFKFB3 treatment also alleviated H2O2-induced DNA fragmentation and reactive oxygen species formation in HT22 cells. In gerbils, the intraperitoneal administration of 2mg/kg Tat-PFKFB3 efficiently delivered the substance to all hippocampal areas, including the hippocampal CA1 region. This administration significantly mitigated ischemia-induced hyperlocomotion, long-term memory deficits, and ischemic neuronal death in the hippocampal CA1 region after ischemia. Additionally, treatment with 2mg/kg Tat-PFKFB3 significantly ameliorated the translocation of Cdk5 from the cytosol to the nucleus in the hippocampal CA1 region 24h after ischemia, but not in other regions. The treatment also significantly reduced reactive oxygen species formation in the CA1 region. These findings suggest that Tat-PFKFB3 reduces neuronal damage in the hippocampal CA1 region after ischemia through the reduction of Cdk5 signaling and reactive oxygen species formation. Therefore, Tat-PFKFB3 may have potential applications in reducing ischemic damage.