EEG decoding reveals task-dependent recoding of sensory information in working memory.

Working memory (WM) supports future behavior by retaining perceptual information obtained in the recent past. The present study tested the hypothesis that WM recodes sensory information in a format that better supports behavioral goals. We recorded EEG while participants performed color delayed-estimation tasks where the colorwheel for the response was either randomly rotated or held fixed across trials. Accordingly, observers had to remember the exact colors in the Rotation condition, whereas they could prepare for a response based on the fixed mapping between the colors and their corresponding locations on the colorwheel in the No-Rotation condition. Results showed that the color reports were faster and more precise in the No-Rotation condition even when exactly the same set of colors were tested in both conditions. To investigate how the color information was maintained in the brain, we decoded the color using a multivariate EEG classification method. The decoding was limited to the stimulus encoding period in the Rotation condition, whereas it continued to be significant during the maintenance period in the No-Rotation condition, indicating that the color information was actively maintained in the condition. Follow-up analyses suggested that the prolonged decoding was not merely driven by the covert shift of attention but rather by the recoding of sensory information into an action-oriented response format. Together, these results provide converging evidence that WM flexibly recodes sensory information depending on the specific task context to optimize subsequent behavioral performance.

Prevalence and clinical features of carotid artery web in patients undergoing endovascular thrombectomy for acute ischemic stroke.

PURPOSE: Carotid artery web (CaW) is a rare focal fibromuscular dysplasia that can lead to embolic strokes with large vessel occlusion. This condition can be effectively treated with endovascular thrombectomy (EVT). Our study aims to assess the prevalence of CaW among patients with acute ischemic stroke (AIS) who underwent EVT and to compare the clinical characteristics of CaW with other carotid artery pathologies. METHODS: We enrolled consecutive patients with AIS who underwent EVT at a single medical center and two regional teaching hospitals in Taiwan from September 2014 to December 2021. We compared CaW with carotid dissection (CaD) and carotid large artery atherosclerosis (CaLAA) in terms of patient demographics and thrombus histological findings. RESULTS: Of the 576 AIS patients who underwent EVT, four (mean age: 50 years) were diagnosed with CaW, resulting in a prevalence of 0.69%. Among these four patients, three experienced successful reperfusion after EVT and achieved functional independence (defined as a modified Rankin Scale score ≤2) three months post-stroke. Importantly, none of the CaW patients suffered a recurrent stroke within one year. Patients with CaW were younger than those with CaD or CaLAA, and exhibited fewer vascular risk factors. Additionally, CaW was associated with distal occlusion sites. The thrombus composition in CaW patients was similar to that in CaD patients. CONCLUSIONS: In conclusion, CaW is a rare finding among Asian patients with carotid artery disease who undergo for AIS. It is more prevalent in younger patients with a limited number of vascular risk factors.

Targeting nanoparticle-conjugated microbubbles combined with ultrasound-mediated microbubble destruction for enhanced tumor therapy.

The stress of the abnormal stromal matrix of solid tumors is a major limiting factor that prevents drug penetration. Controlled, accurate, and efficient delivery of theranostic agents into tumor cells is crucial. Combining ultrasound with nanocarrierbased drug delivery systems have become a promising approach for targeted drug delivery in preclinical cancer therapy. In this study, to ensure effective tumor barrier penetration, access to the tumor microenvironment, and local drug release, we designed targeted nanoparticle (NP)-conjugated microbubbles (MBs); ultrasound could then help deliver acoustic energy to release the NPs from the MBs. The ultrasound-targeted MB destruction (UTMD) system of negatively charged NPs was conjugated with positively charged MBs using an ionic gelation method. We demonstrated the transfer of targeted NPs and their entry into gastric cancer cells through ligand-specific recognition, followed by enhanced cell growth inhibition owing to drug delivery-induced apoptosis. Moreover, the UTMD system combining therapeutic and ultrasound image properties can effectively target gastric cancer, thus significantly enhancing antitumor activity, as evident by tumor localization in an orthotopic mouse model of gastric cancer. The combination of ultrasound and NP-based drug delivery systems has become a promising approach for targeted drug delivery in preclinical cancer therapy.

Mangiferin induces immune responses and evaluates the survival rate in WEHI-3 cell generated mouse leukemia in vivo.

Mangiferin is a naturally occurring polyphenol, widely distributed in Thymeraceae families, and presents pharmacological activity, including anti-cancer activities in many human cancer cell lines. Mangiferin has also been reported to affect immune responses; however, no available information concerning the effects of mangiferin on immune reactions in leukemia mice in vivo. In the present study, we investigated the effects of mangiferin on leukemia WEHI-3 cell generated leukemia BLAB/c mice. Overall, the experiments were divided into two parts, one part was immune responses experiment and the other was the survival rate experiment. The immune responses and survival rate study, 40 mice for each part, were randomly separated into five groups (N = 8): Group I was normal animals and groups II-V WEHI-3 cell generated leukemia mice. Group II mice were fed normal diet as a positive control; group III, IV, and V mice received mangiferin at 40, 80, and 120 mg/kg, respectively, by intraperitoneal injection every 2 days for 20 days. Leukocytes cell population, macrophage phagocytosis, and NK cell activities were analyzed by flow cytometry. Isolated splenocytes stimulated with lipopolysaccharide (LPS) and concanavalin A (Con A) were used to determine the proliferation of B and T cells, respectively, and subsequently were analyzed by flow cytometry. Results indicated that mangiferin significantly increased body weight, decreased the liver and spleen weights of leukemia mice. Mangiferin also increased CD3 T-cell and CD19 B cell population but decreased Mac-3 macrophage and CD11b monocyte. Furthermore, mangiferin decreased phagocytosis of macrophages from PBMC and peritoneal cavity at 40, 80, and 120 mg/kg treatment. However, it also increased NK cell activity at 40 and 120 mg/kg treatment. There were no effects on T and B cell proliferation at three examined doses. In survival rate studies, mangiferin significantly elevated survival rate at 40 and 120 mg/kg treatment of leukemia mice in vivo.

Endovascular Treatment Outcome and CT Angiography Findings in Acute Basilar Artery Occlusion with and without Underlying Intracranial Atherosclerotic Stenosis.

PURPOSE: To compare clinical characteristics and treatment outcomes of intra-arterial thrombectomy (IAT) in acute basilar artery occlusion (BAO) with and without underlying intracranial atherosclerotic stenosis (ICAS) and to investigate the usefulness of preprocedural CT angiography findings in the diagnosis of ICAS. MATERIALS AND METHODS: Twenty patients who received IAT for acute BAO between September 2014 and March 2019 were included. Additional therapies such as angioplasty, stent placement, and tirofiban infusion were provided while treating ICAS. Clinical and angiographic results of treatment were recorded. Preprocedural CT angiography findings in ICAS and non-ICAS groups were compared to assess (i) basilar tip opacification, (ii) partial occlusion, (iii) presence of convex border, (iv) occlusion segment longer than two thirds of the basilar artery or 20 mm, (v) dense basilar artery, and (vi) wall calcification in the occluded segment. RESULTS: Among the 20 patients (mean age, 71.3 y; mean stroke score, 24.8), optimal recanalization was achieved in 19 (95%). Three patients had good clinical outcomes. There were 6 patients with underlying ICAS. No difference was observed between ICAS and non-ICAS groups in terms of optimal angiographic recanalization and good outcome. On CT angiography, basilar tip occlusion (100% vs 29%), partial occlusion (100% vs 83%), and long occlusion length (100% vs 14%) significantly differed between the groups (P ≤ .01). CONCLUSIONS: In acute BAO, underlying ICAS does not affect optimal recanalization rate or clinical outcome. Preprocedural CT angiography is a potentially useful tool to detect it.

Novel circulating tumor cell-based blood test for the assessment of PD-L1 protein expression in treatment-naïve, newly diagnosed patients with non-small cell lung cancer.

We evaluated the analytical and clinical performance of a novel circulating tumor cell (CTC)-based blood test for determination of programmed death ligand 1 (PD-L1) protein expression status in real time in treatment-naïve non-small cell lung cancer (NSCLC) patients. CTCs were detected in 86% of patients with NSCLC (I-IV) at the time of diagnosis, with a 67% PD-L1 positivity rate (≥ 1 PDL + CTC). Among 33 NSCLC patients with PD-L1 results available via both tissue immunohistochemistry (IHC) and CTC assays, 78.9% were positive according to both methods. The CTC test identified an additional ten cases that were positive for PD-L1 expression but that tested negative via IHC analysis. Detection of higher PD-L1 expression on CTCs compared to that in the corresponding tissue was concordant with data obtained using other platforms in previously treated patients. The concordance in PD-L1 expression between tissue and CTCs was approximately 57%, which is higher than that reported by others. In summary, evaluation of PD-L1 protein expression status on CTCs isolated from NSCLC patients is feasible. PD-L1 expression status on CTCs can be determined serially during the disease course, thus overcoming the myriad challenges associated with tissue analysis.

Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways.

Ouabain, a cardiotonic steroid and specific Na+ /K+ -ATPase inhibitor, has a potential to induce cancer cell apoptosis but the mechanisms of apoptosis induced by ouabain are not fully understand. The aim of this study was to investigate the cytotoxic effects of ouabain on human prostate cancer DU 145 cells in vitro. Cell morphological changes were examined by phase contrast microscopy. Cell viability, cell cycle distribution, cell apoptosis, DNA damage, the production of ROS and Ca2+ , and mitochondrial membrane potential (ΔΨm ) were measured by flow cytometry assay. Results indicated that ouabain induced cell morphological changes, decreased total cell viability, induced G0/G1 phase arrest, DNA damage, and cell apoptosis, increased ROS and Ca2+ production, but decreased the levels of ΔΨm in DU 145 cells. Ouabain also increased the activities of caspase-3, -8, and -9. Western blotting was used for measuring the alterations of apoptosis-associated protein expressions in DU 145 cells and results indicated that ouabain increased the expression of DNA damage associated proteins (pATMSer1981 , p-H2A.XSer139 , and p-p53Ser15 ) and ER-stress-associated proteins (Grp78, ATF6ß, p-PERKThr981 , PERK, eIF2A, GADD153, CaMKIIß, and caspase-4) in time-dependently. Furthermore, ouabain increased apoptosis-associated proteins (DR4, DR5, Fas, Fas Ligand, and FADD), TRAIL pathway, which related to extrinsic pathway, promoted the pro-apoptotic protein Bax, increased apoptotic-associated proteins, such as cytochrome c, AIF, Endo G, caspase-3, -8, and -9, but reduced anti-apoptotic protein Bcl-2 and Bcl-x in DU 145 cells. In conclusion, we may suggest that ouabain decreased cell viability and induced apoptotic cell death may via caspase-dependent and mitochondria-dependent pathways in human prostate cancer DU 145 cells.

Ouabain promotes immune responses in WEHI-3 cells to generate leukemia mice through enhancing phagocytosis and natural killer cell activities in vivo.

Ouabain, a cardiotonic steroid, was used for the treatment of heart failure and atrial fibrillation and induces cancer cell apoptosis in many human cancer cells including human leukemia cells. However, there are no reports to show the effects on immune responses in a leukemia mouse model. In this study, WEHI-3 cell generated leukemia mice were developed and treated by oral ouabain at 0, 0.75, 1.5, and 3 mg/kg for 15 days. Results indicated that ouabain did not affect body appearance, but decreased liver and spleen weights, B- and T-cell proliferation at all three doses treatment and increased CD19 cells at 3.0 mg/kg treatment, decreased CD3, CD11b, and Mac-3 cells levels compared with positive control. Furthermore, ouabain increased the macrophage phagocytosis from peripheral blood mononuclear cell and peritoneal cavity at all three doses treatment and increased NK cell activities. Ouabain restored GOT, GPT and LDH levels in WEHI-3 leukemia mice in vivo.

Interactive OCT-Based Tooth Scan and Reconstruction.

Digital dental reconstruction can be a more efficient and effective mechanism for artificial crown construction and period inspection. However, optical methods cannot reconstruct those portions under gums, and X-ray-based methods have high radiation to limit their applied frequency. Optical coherence tomography (OCT) can harmlessly penetrate gums using low-coherence infrared rays, and thus, this work designs an OCT-based framework for dental reconstruction using optical rectification, fast Fourier transform, volumetric boundary detection, and Poisson surface reconstruction to overcome noisy imaging. Additionally, in order to operate in a patient's mouth, the caliber of the injector is small along with its short penetration depth and effective operation range, and thus, reconstruction requires multiple scans from various directions along with proper alignment. However, flat regions, such as the mesial side of front teeth, may not have enough features for alignment. As a result, we design a scanning order for different types of teeth starting from an area of abundant features for easier alignment while using gyros to track scanned postures for better initial orientations. It is important to provide immediate feedback for each scan, and thus, we accelerate the entire signal processing, boundary detection, and point-cloud alignment using Graphics Processing Units (GPUs) while streamlining the data transfer and GPU computations. Finally, our framework can successfully reconstruct three isolated teeth and a side of one living tooth with comparable precisions against the state-of-art method. Moreover, a user study also verifies the effectiveness of our interactive feedback for efficient and fast clinic scanning.

OCT-Based Periodontal Inspection Framework.

Periodontal diagnosis requires discovery of the relations among teeth, gingiva (i.e., gums), and alveolar bones, but alveolar bones are inside gingiva and not visible for inspection. Traditional probe examination causes pain, and X-ray based examination is not suited for frequent inspection. This work develops an automatic non-invasive periodontal inspection framework based on gum penetrative Optical Coherence Tomography (OCT), which can be frequently applied without high radiation. We sum up interference responses of all penetration depths for all shooting directions respectively to form the shooting amplitude projection. Because the reaching interference strength decays exponentially with tissues' penetration depth, this projection mainly reveals the responses of the top most gingiva or teeth. Since gingiva and teeth have different air-tissue responses, the gumline, revealing itself as an obvious boundary between teeth and gingiva, is the basis line for periodontal inspection. Our system can also automatically identify regions of gingiva, teeth, and alveolar bones from slices of the cross-sectional volume. Although deep networks can successfully and possibly segment noisy maps, reducing the number of manually labeled maps for training is critical for our framework. In order to enhance the effectiveness and efficiency of training and classification, we adjust Snake segmentation to consider neighboring slices in order to locate those regions possibly containing gingiva-teeth and gingiva-alveolar boundaries. Additionally, we also adapt a truncated direct logarithm based on the Snake-segmented region for intensity quantization to emphasize these boundaries for easier identification. Later, the alveolar-gingiva boundary point directly under the gumline is the desired alveolar sample, and we can measure the distance between the gumline and alveolar line for visualization and direct periodontal inspection. At the end, we experimentally verify our choice in intensity quantization and boundary identification against several other algorithms while applying the framework to locate gumline and alveolar line in vivo data successfully.

Frailty as a Predictor of Future Fracture in Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Studies have identified frailty as an effective predictor of fracture; however, the correlation between frailty and fracture differs between various stages of frailty. OBJECTIVES: The main aim is to determine the correlation between various stages of frailty and fracture risk; a secondary purpose is to determine the correlation between subgroups (e.g., females, females with a hip fracture, or aged 65 years or older) within the stages of frailty and fracture risk. Finally, effect of frailty criteria on the association between stages of frailty and fracture risk was tested. METHODS: We conducted a systematic review and meta-analysis. The inclusion criteria were as follows: (a) a prospective study design; (b) subjects aged 55 years or older; (c) a division into robust, prefrail, and frail groups; and (d) reported confidence intervals of hazard ratio. Two investigators independently assessed quality and discussed their findings to reach consensus. The quality of the literature was assessed and the level of evidence was also determined. RESULTS: In total, five studies included 103,783 older people and recorded 2,960 fractures. The results identified that the risk of fracture in the frail people was higher than that in both the robust people (summary HR: 1.67; 95% CI [1.46-1.91]) and prefrail people (summary HR: 1.28; 95% CI [1.16-1.40], and that the risk of fracture in the prefrail people was higher than that in the robust people (summary HR: 1.30; 95% CI [1.20-1.41]). A subgroup analysis revealed that among female adults, older females with hip fracture, or those aged 65 years or more, those who were categorized as frail showed the highest fracture risk, followed by those who were categorized as prefrail. LINKING EVIDENCE TO ACTION: Professional nurses caring for frail or prefrail people should actively develop fracture prevention measures to reduce the risk of death caused by fractures.

Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: thalamic lesions.

BACKGROUND: Tumors with epicenter in the thalamus occur in about 4 % of pediatric brain tumors. The histological diagnosis is mainly gliomas. Among them, low-grade glioma (LGG) constituted of a significant entity of the tumors (Cuccia et al., Childs Nerv Syst 13:514-521, 1997; Puget et al., J Neurosurg 106:354-362, 2007; Bernstein et al., J Neurosurg 61:649-656, 1984; Bilginer et al., Childs Nerv Syst 30:1493-1498, 2014). Since Kelly's report in 1989, >90 % resection of thalamic tumors were achieved in reported series (Ozek and Ture, Childs Nerv Syst 18:450-6, 2002; Villarejo et al., Childs Nerv Syst 10:111-114, 1994; Moshel et al., Neurosurgery 61:66-75, 2007; Albright, J Neurosurg 100(5 Suppl Pediatrics): 468-472, 2004; Kelly, Neurosurgery 25:185-195, 1989; Drake et al., Neurosurgery 29: 27-33, 1991). MATERIALS AND METHODS: Sixty-nine cases of thalamic tumors in children were retrospectively reviewed. There were 25 cases of LGGs. We analyzed our experience and correlated it with reported series. RESULTS: Summing up of 4 reported series and the present series, there were 267 cases of thalamic tumors in children. Among these tumors, 107 (40.1 %) were LGGs and 91 (34.1 %) were low-grade astrocytomas (LGAs). In the present series, all of the 25 LGGs were LGAs that consisted of 11 pilocytic astrocytomas (PAs) and 14 diffuse astrocytomas (DAs). Six cases received biopsy sampling only. The remaining 19 cases received different degrees of surgical resection via several approaches. Radical (>90 %) resection was achieved better in PAs comparing with DAs. There was no operative mortality. Two patients had increased neurological deficits. In a mean follow-up period of 11.9 years, three patients died of tumor progression and one patient died of anaplastic change. The 5- and 10-year overall survival (OS) was 87.1 and 87.1 %, respectively. CONCLUSION: Thalamic LGGs are mainly LGAs and are indolent. The rate of >90 % resection was relatively low in the present series. By applying contemporary diagnostic MRI studies, surgical facilities, and appropriate approaches in selective cases, we may try maximum neuroprotective radical (>90 %) resection.

Acquired Chiari malformation type I associated with a supratentorial fistulous arteriovenous malformation: a case report.

A case of acquired Chiari malformation type I with frontal fistulous arteriovenous malformation (AVM) is presented, and the pathophysiology is discussed. The tonsillar herniation and hydrocephalus both resolved after AVM was excised. This case provides some insight into the complex hemodynamic change exerted by the fistulous AVM and the mechanism of the development of acquired Chiari malformation type I.

Factors affecting survival of medulloblastoma in children: the changing concept of management.

Medulloblastoma (MB) is a type of malignant tumor arising only in the cerebellum that was first defined by Cushing and Bailey in 1920s. In this review paper, we trace the evolution of risk stratification and the correlated changing concept of management in the past years. Outcome analysis of the hospital series of the Taipei Veterans General Hospital, Cheng Hsin General Hospital, and Taipei Medical University Hospital was performed to correlate prognostic indicators with reported studies. The purpose is to provide clues for age-specific and risk-adjusted optimal, effective, but beneficial and protective treatment strategies of these tumors in children.

Working memory flips the direction of serial bias through memory-based decision.

Reported perception of a new stimulus is either attracted toward or repelled away from task-irrelevant prior stimuli. While prevailing theories propose that the opposing serial biases may stem from distinct stages of information processing, the exact role of working memory (WM) in the serial bias remains unclear despite its consistent involvement in nearly all pertinent studies. Additionally, it is not well understood whether this bias is primarily driven by the biased representation itself or by the decision-making process for the new stimulus. In the present study, we used an orientation delayed estimation paradigm with an attention-demanding intervening task, designed to disrupt the maintenance of stimulus information to investigate the role of WM in serial bias. In the analysis, we scrutinized the trajectory of mouse reports and response time to investigate how the response unfolds over time. Our findings indicate that the serial bias went from repulsive to attractive when WM maintenance was interrupted by the intervening task, and that the associated response trajectories and response time exhibited patterns that cannot be explained by the biased representation alone. These results demonstrate that the task-irrelevant prior stimulus influences the decision for the new stimulus, with the direction of the bias being determined by attentional demand during WM maintenance, thereby placing significant constraints on existing theories on the serial bias effect.

Recombinant soluble form of receptor for advanced glycation end products ameliorates microcirculation impairment and neuroinflammation after subarachnoid hemorrhage.

Impaired cerebral microcirculation after subarachnoid hemorrhage (SAH) has been shown to be related to delayed ischemic neurological deficits (DIND). We previously demonstrated the involvement of the receptor for advanced glycation end products (RAGE) in the pathogenesis of SAH related neuronal death. In the present study, we aimed to investigate the therapeutic effects of a recombinant soluble form of RAGE (sRAGE) on microcirculation impairment following SAH. Intrathecal injection of autologous blood in rats, mixed primary astrocyte and microglia cultures exposed to hemolysates and endothelial cells â€‹(ECs) from human brain microvascular exposed to glia-conditioned medium or SAH patient's CSF were used as experimental SAH models in vivo and in vitro. The results indicated that intrathecal administration of recombinant sRAGE significantly ameliorated the vasoconstriction of cortical arterioles and associated perfusion impairment, brain edema, reduced cell death, endothelial dysfunction, and improved motor performance at 24 and 48 â€‹h after SAH induction in rats. The in vitro results further showed that recombinant sRAGE significantly reduced astrocyte swelling and microglia activation, in parallel with decreased mRNA expression levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in vitro. Moreover, the in vitro model of SAH-induced p-eNOS and eNOS suppression, along with stress fiber formation in brain microvascular ECs, was effectively reversed by sRAGE treatment and led to a decrease in cleaved-caspase 3 expression. In summary, recombinant sRAGE effectively lessened microcirculation impairment and vascular injury after SAH via the mechanism of anti-inflammation, which may provide a potential therapeutic strategy for SAH.

Nanoparticles for Augmenting Therapeutic Potential and Alleviating the Effect of Di(2-ethylhexyl) Phthalate on Gastric Cancer.

Changes in diet culture and modern lifestyle contributed to a higher incidence of gastrointestinal-related diseases, including gastritis, implicated in the pathogenesis of gastric cancer. This observation raised concerns regarding exposure to di(2-ethylhexyl) phthalate (DEHP), which is linked to adverse health effects, including reproductive and developmental problems, inflammatory response, and invasive adenocarcinoma. Research on the direct link between DEHP and gastric cancer is ongoing, and further studies are required to establish a conclusive association. In our study, extremely low concentrations of DEHP exerted significant effects on cell migration by promoting the epithelial-mesenchymal transition in gastric cancer cells. This effect was mediated by the modulation of the PI3K/AKT/mTOR and Smad2 signaling pathways. To address the DEHP challenges, our initial design of TPGS-conjugated fucoidan, delivered via pH-responsive nanoparticles, successfully demonstrated binding to the P-selectin protein. This achievement has not only enhanced the antigastric tumor efficacy but has also led to a significant reduction in the expression of malignant proteins associated with the condition. These findings underscore the promising clinical therapeutic potential of our approach.

Nanoparticle-enhanced postbiotics: Revolutionizing cancer therapy through effective delivery.

AIM: Gastric cancer contributes to cancer-related fatalities. Conventional chemotherapy faces challenges due to severe adverse effects, prompting recent research to focus on postbiotics, which are safer biomolecules derived from nonviable probiotics. Despite promising in vitro results, efficient in vivo delivery systems remain a challenge. This study aimed to design a potential nanoparticle (NP) formulation encapsulating the Lacticaseibacillus paracasei GMNL-133 (SGMNL-133) isolate to enhance its therapeutic efficacy in treating gastric cancer. MAIN METHODS: We successfully isolated GMNL-133 (SGMNL-133) by optimizing the lysate extraction and column elution processes for L. paracasei GMNL-133, resulting in substantial enhancement of its capacity to inhibit the proliferation of gastric cancer cells. Additionally, we developed a potential NP utilizing arginine-chitosan and fucoidan encapsulating SGMNL-133. KEY FINDINGS: This innovative approach protected the SGMNL-133 from degradation by gastric acid, facilitated its penetration through the mucus layer, and enabled interaction with gastric cancer cells. Furthermore, in vivo experiments demonstrated that the encapsulation of SGMNL-133 in NPs significantly enhanced its efficacy in the treatment of orthotopic gastric tumors while simultaneously reducing tissue inflammation levels. SIGNIFICANCE: Recent research highlights postbiotics as a safe alternative, but in vivo delivery remains a challenge. Our study optimized the extraction of the lysate and column elution of GMNL-133, yielding SGMNL-133. We also developed NPs to protect SGMNL-133 from gastric acid, enhance mucus penetration, and improve the interaction with gastric cancer cells. This combination significantly enhanced drug delivery and anti-gastric tumor activity.

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.

BACKGROUND AND OBJECTIVES: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF). METHODS: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56. RESULTS: Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated. CONCLUSION: Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.