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Yu-Wen Cheng,1 Ta-Fu Chen,2 Ming-Jang Chiu2,3 1Department of Neurology, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan; 2Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Department of Psychology, College of Science, National Taiwan University, Taipei, Taiwan Abstract: Identification of subjects at the early stages of Alzheimer’s disease (AD) is fundamental for drug development and possible intervention or prevention of cognitive decline. The concept of mild cognitive impairment (MCI) evolved during the past two decades to define subjects at the transitional stage between normal aging and dementia. Evidence from cross-sectional and longitudinal studies has shown that MCI is associated with an increased risk of positive AD biomarkers and an increased annual conversion rate of 5%–17% to AD. The presence of AD biomarkers in subjects with MCI was associated with an even higher risk of progression to dementia. However, earlier clinical trials for pharmacotherapy in subjects with MCI were disappointing. To extend the spectrum of AD to an earlier stage before MCI, subjective cognitive decline (SCD) was introduced and was defined as self-reported cognitive decline before the deficits could be detected by cognitive tests. Subjects with SCD have an increased risk of underlying AD pathology. However, SCD can also develop secondary to other heterogeneous etiologies, including other neurodegenerative and psychiatric diseases, personality traits, physical conditions, and medication use. Several clinical and biomarker features were proposed to predict risk of conversion to AD in subjects with SCD. Further longitudinal studies are needed to support the validity of these high-risk features. Keywords: mild cognitive impairment, subjective cognitive decline, preclinical Alzheimer’s disease, Alzheimer’s disease

Chi-Wen Chou,1,2 Ya-Wen Cheng,3 Chung-Hung Tsai1 1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 2Department of Orthopedics Surgery, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan; 3Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, TaiwanObjective: Bamboo is distributed worldwide, and its different parts are used as foods or as a traditional herb. Recently, antitumoral effects of bamboo extracts on several tumors have been increasingly reported; however, antitumoral activity of bamboo extracts on osteosarcoma remains unclear. In the present study, we investigated effects of an aqueous Phyllostachys edulis leaf extract (PEE) on osteosarcoma cells and the underlying mechanism of inhibition. Methods: The growth of human osteosarcoma cell lines 143B and MG-63 and lung fibroblast MRC-5 cells was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Apoptosis was demonstrated using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay and flow cytometric analysis. Phosphorylation and protein levels were determined by immunoblotting. Results: After treatment with PEE, viability of 143B and MG-63 cells was dose-dependently reduced to 36.3%±1.6% of control values, which were similar to AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside) treatments. In parallel, ratios of apoptotic cells and cells in the sub-G1 phase were significantly increased. Further investigation showed that PEE treatments led to activation of caspase cascades and changes of apoptotic mediators Bcl2, Bax, and p53. Consistently, our results revealed that PEE activated adenosine monophosphate-activated protein kinase (AMPK) signaling, and the AMPK activation was associated with the induction of apoptotic signaling. Conclusion: Our results indicated that PEE suppressed the growth of 143B and MG-63 cells but moderately affected MRC-5 cells. PEE-induced apoptosis may attribute to AMPK activation and the following activation of apoptotic signaling cascades. These findings revealed that PEE possesses antitumoral activity on human osteosarcoma cells by manipulating AMPK signaling, suggesting that PEE alone or combined with regular antitumor drugs may be beneficial as osteosarcoma treatments.Keywords: bamboo, antitumor, AMPK, Bcl2, Bax

Background and Purpose Hypoxia-mediated neovascularization plays an important role in age-related macular degeneration ( AMD). There are few animal models or effective treatments for AMD. Here, we investigated the effects of the flavonoid silibinin on hypoxia-induced angiogenesis in a rat AMD model. Experimental Approach Retinal pigmented epithelial ( RPE) cells were subjected to hypoxia in vitro and the effects of silibinin on activation of key hypoxia-induced pathways were examined by elucidating the hypoxia-inducible factor-1 alpha ( HIF-1 α) protein level by Western blot. A rat model of AMD was developed by intravitreal injection of VEGF in Brown Norway rats, with or without concomitant exposure of animals to hypoxia. Animals were treated with oral silibinin starting at day 7 post- VEGF injection and AMD changes were followed by fluorescein angiography on days 14 and 28 post-injection. Key Results Silibinin pretreatment of RPE cells increased proline hydroxylase-2 expression, inhibited HIF-1 α subunit accumulation, and inhibited VEGF secretion. Silibinin-induced HIF-1 α and VEGF down-regulation required suppression of hypoxia-induced phosphatidylinositol 3-kinase/ Akt/mammalian target of rapamycin ( mTOR) pathway. In the rat model of AMD, silibinin administration prevented VEGF- and VEGF plus hypoxia-induced retinal oedema and neovascularization. Conclusion and Implications The effects of silibinin, both in vitro and in vivo, support its potential as a therapeutic for the prevention of neovascular AMD. [ABSTRACT FROM AUTHOR]

There is much evidence indicating that human leukemic cells and monocytes/macrophages synthesize, and secrete, several matrix metalloproteinases (MMPs), and participate in the degradation of extracellular matrix components in tissue lesions. In this study, we investigated the effects and mechanisms of andrographolide, extracted from the herb Andrographis paniculata, on human monocytic MMPs expression and activation. Andrographolide (1-50 μM) exhibited concentration-dependent inhibition of MMP-9 activation, induced by either tumor necrosis factor-α (TNF-α), or lipopolysaccharide (LPS), in THP-1cells. In addition, andrographolide did not present an inhibitory effect on MMP-9 enzymatic activity at a concentration of 50 μM. By contrast, enzyme-linked immunosorbent assay (ELISA) showed that andrographolide partially affect TIMP-1 levels. Western blot analysis showed that both TNF-α, and LPS stimulators attenuated MMP-9 protein expression in a concentration-dependent manner. Using reverse transcription polymerase chain reaction (RT-PCR), we found that andrographolide suppressed expression of MMP-9 messenger RNA. Furthermore, we also found that andrographolide could significantly inhibit the degradation of inhibitor-κB-α (IκB-α) induced by TNF-α. We used electrophoretic mobility shift assay and reporter gene detection to show that andrographolide also markedly inhibited NF-κB signaling, anti-translocation and anti-activation. In conclusion, we demonstrate that andrographolide attenuates MMP-9 expression, and its main mechanism might involve the NF-κB signal pathway. These results provide new opportunities for the development of new anti-inflammatory and leukemic therapies. [ABSTRACT FROM AUTHOR]

AIM OF THE STUDY: Shikonin/alkannin (SA) derivatives, analogs of naphthoquinone pigments, are the major components of root extracts of the Chinese medicinal herb (Lithospermum erythrorhizon; LE) and widely distributed in several folk medicines. In the present study, the effect and the underline molecular mechanism of shikonin derivatives isolated from root extracts of Lithospermum euchroma on lipopolysaccharide (LPS)-induced inflammatory response were investigated. MATERIALS AND METHODS: Effects of five SA derivatives, including SA, acetylshikonin, beta,beta-dimethylacrylshikonin, 5,8-dihydroxy-1.4-naphthoquinone, and 1,4-naphthoquinone on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in mouse macrophage RAW264.7 cells were examined. RESULTS: Data suggested that SA derivatives inhibited LPS-induced NO and PGE(2) production, and iNOS protein expression. RT-PCR analysis showed that SA derivatives diminished LPS-induced iNOS mRNA expression. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in LPS-stimulated RAW 264.7 cells was concentration-dependently suppressed by SA derivatives. SA inhibited NF-kappaB activation by prevention of the degradation of inhibitory factor-kappaB and p65 level in nuclear fractions induced by LPS. CONCLUSIONS: Taken together, these results suggest that the anti-inflammatory properties of SA derivatives might result from inhibition of iNOS protein expression through the downregulation of NF-kappaB activation via suppression of phosphorylation of ERK, in LPS-stimulated RAW 264.7 cells. [ABSTRACT FROM AUTHOR]

In this paper we introduce a new method for producing nanoscale spin valve arrays. The deposition of NiFe/Cu/NiFe/MnNi spin valve structures was carried out in self-organized nanoporous anodized aluminium templates by using an electrodeposition technique involving three baths of different solutions. Field emission scanning electron microscopy observation reveals that the nanometric spin valve arrays, of uniform size, are well separated and exhibit a very perfect two-dimensional array with a hexagonal pattern. Post-thermal treatment yields highly 〈111〉 oriented spin valve films with a giant magnetoresistance ratio of above 4%. The pinning field is about 700 Oe for the nanoscale spin valves film and it stays constant up to 200 °C. These nanoscale spin valve arrays are highly thermally stable and, thus, suitable for the application of high density recording heads. [ABSTRACT FROM AUTHOR]

Background: Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect uterus; however, their biological behaviors are quite different. This distinction has clinical significance, because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate 3 different scoring mechanisms of p16INK4a immunohistochemical (IHC) staining in distinguishing between primary ECAs and EMAs.Methods: A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded tissue from hysterectomy specimens, including 14 ECAs and 24 EMAs. Tissue array sections were immunostained with a commercially available antibody of p16INK4a. Avidin-biotin complex (ABC) method was used for antigens visualization. The staining intensity and area extent of the IHC reactions was evaluated using the semi-quantitative scoring system. The 3 scoring methods were defined on the bases of the following: (1) independent cytoplasmic staining alone (Method C), (2) independent nucleic staining alone (Method N), and (3) mean of the sum of cytoplasmic score plus nucleic score (Method Mean of C plus N).Results: Of the 3 scoring mechanisms for p16INK4a expression, Method N and Method Mean of C plus N showed significant (p-values < 0.05), but Method C showed non-significant (p = 0.245) frequency differences between ECAs and EMAs. In addition, Method Mean of C plus N had the highest overall accuracy rate (81.6%) for diagnostic distinction among these 3 scoring methods.Conclusion: According to the data characteristics and test effectiveness in this study, Method N and Method Mean of C plus N can significantly signal to distinguish between ECAs and EMAs; while Method C cannot do. Method Mean of C plus N is the most promising and favorable means among the three scoring mechanisms. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study was undertaken to investigate the differences in perinatal outcomes among Asian American/Pacific Islander (AAPI) women. STUDY DESIGN: A retrospective cohort study of all Japanese, Chinese, and Filipina women who delivered at University of California, San Francisco from 1985 to 2001 examined the incidence of gestational diabetes, preeclampsia, and preterm delivery. RESULTS: Among the 6511 women delivered during the study period, the incidence of preeclampsia was highest among Filipina women (6.8%) compared with the Chinese and Japanese women (4.0% and 3.7%, respectively, P < .001). Gestational diabetes was most common in the Chinese and Filipina women (6.5% and 6.1%, respectively) compared with the Japanese women (3.4%, P = .013). Preterm delivery was also highest among Filipina women both before 37 weeks (12.2%, P < .001) and 34 weeks (4.8%, P = .004). These differences remained statistically significant after controlling for potential confounding variables. CONCLUSION: We found significant differences in rates of preeclampsia, gestational diabetes, and preterm delivery in the Chinese, Japanese, and Filipino subgroups. In studies of race and ethnicity, it is important to examine Asian subgroups separately. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to examine whether women with one elevated value of the 3-hour glucose tolerance test are at increased risk for adverse perinatal outcomes. STUDY DESIGN: This was a retrospective cohort study of singleton pregnancies that were screened for gestational diabetes mellitus with the use of the glucose loading test and with a glucose tolerance test for follow up, if screened values were positive. Perinatal outcomes in women with one elevated glucose tolerance test value were compared with the outcomes in women who screened negative by glucose loading test. The chi-square test was used to compare categorical outcomes, and multivariate logistic regression analysis was used to control for potential confounding factors; a P value of < .05 indicated statistical significance. RESULTS: Of 14,036 women who met the study criteria, women with one elevated glucose tolerance test value exhibited higher rates of cesarean delivery (in nulliparous women only), preeclampsia, chorioamnionitis, birth weight > 4000 g and > 4500 g, and neonatal admission to the intensive care nursery as compared with women who screened negative (P < .05 for all). CONCLUSION: Although women with one elevated glucose tolerance test value are not diagnosed with gestational diabetes mellitus, they are still at risk for adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to identify associated characteristics of face presentation and to examine factors that were associated with mode of delivery in the setting of face presentation. STUDY DESIGN: This was a retrospective cohort study of women who were diagnosed with face presentation during labor. We examined maternal, fetal, and labor characteristics to determine the associations and predictors of cesarean delivery. RESULTS: Fetuses in face presentation were more likely preterm, < 2500 g, and black. An Apgar score of < 7 at 5 minutes was more common in face presentation (10.9%) compared with vertex presentation (4.4%; P = .018). Rates of umbilical artery base excess < -12 or pH < 7.0 were not different. Cesarean delivery was less common in women who received oxytocin (adjusted odds ratio, 0.18; 95% CI, 0.03-0.95) and in women with mentum anterior (14%) as compared with mentum posterior presentation (85%; P < .001). CONCLUSION: This study confirms the association between face presentation and prematurity. The association with black ethnicity may be related to differences in pelvic anatomy. Although face presentation was associated with decreased Apgar scores, no other indicators of fetal asphyxia were identified. Cesarean delivery rates were higher in women with mentum posterior face presentation and in women who did not receive oxytocin. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of the study was to define predictors of successful rotation and rate of cesarean delivery after manual rotation of the fetal occiput from occiput posterior or transverse position. STUDY DESIGN: A retrospective cohort study comprised patients who underwent a trial of manual rotation of the fetal occiput from occiput posterior or occiput transverse position. Successful rotation was defined as delivery in the occiput anterior position. We examined maternal, fetal, and labor characteristics as predictors of both fetal position at delivery and cesarean delivery. RESULTS: Multiparity (odds ratio, 2.5; 95% CI, 1.5-3.8) and maternal age < 35 years (odds ratio, 2.0; 95% CI, 1.1-3.4) were associated with successful manual rotation of the fetal occiput. After successful rotation, the cesarean delivery rate was 2%, compared with 34% if the rotation failed (P < .001). Asian ethnicity, nulliparity, age > 35 years, labor induction, and epidural usage were associated with higher rates of cesarean delivery. CONCLUSION: After successful manual rotation of the fetal occiput, women had lower cesarean delivery rates than women with unsuccessful rotations. Multiparity and maternal age of < 35 years were associated with more successful rotations. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to investigate the outcomes that are associated with pregnancy and treated hypothyroidism. STUDY DESIGN: This was a retrospective cohort study of all women who received prenatal care and were delivered at the University of California, San Francisco, between 1989 and 2001. All patients with hypothyroidism diagnosed before pregnancy or early in pregnancy were identified. Maternal, fetal, and obstetric outcomes were then collected and analyzed for women with hypothyroidism and compared with women without hypothyroidism. RESULTS: Among 20,499 deliveries, there were 419 women (2.1%) who were treated for hypothyroidism during the study period. Hypothyroidism was more common among women > or =35 years old, white women, and women without Medicaid insurance. Treated hypothyroidism was not associated with any increase in maternal, fetal, or neonatal complications. In addition, hypothyroidism did not affect mode of delivery. CONCLUSION: Compared with patients without hypothyroidism, patients with treated hypothyroidism are not at any increased risk for perinatal morbidity. [ABSTRACT FROM AUTHOR]

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., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Aims: Currently, there is limited data on prognostic indicators after insertion of percutaneous ventricular assist device (PVAD) in the treatment of cardiogenic shock (CS). This study evaluated the prognostic role of cardiac power output (CPO) ratio, defined as CPO at 24 h divided by early CPO (30 min to 2 h), in CS patients after PVAD., Methods and Results: Consecutive CS patients from the QEH-PVAD Registry were followed up for survival at 90 days after PVAD. Among 121 consecutive patients, 98 underwent right heart catheterization after PVAD, with CPO ratio available in 68 patients. The CPO ratio and 24-h CPO, but not the early CPO post PVAD, were significantly associated with 90-day survival, with corresponding area under curve in ROC analysis of 0.816, 0.740, and 0.469, respectively. In multivariate analysis, only the CPO ratio and lactate level at 24 h remained as independent survival predictors. The CPO ratio was not associated with age, sex, and body size. Patients with lower CPO ratio had significantly lower coronary perfusion pressure, worse right heart indices, and higher pulmonary vascular resistance. A lower CPO ratio was also significantly associated with mechanical ventilation and higher creatine kinase levels in myocardial infarction patients., Conclusion: In post-PVAD patients, the CPO ratio outperformed the absolute CPO values and other haemodynamic metrics in predicting survival at 90 days. Such a proportional change of CPO over time, likely reflecting native heart function recovery, may help to guide management of CS patients post-PVAD., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Mechanical strain substantially influences tissue shape and function in various contexts, from embryonic development to disease progression. Disruptions in these processes can result in congenital abnormalities and short-circuit mechanotransduction pathways. Manipulating strain in live tissues is crucial for understanding its impact on cellular and subcellular activities. Existing tools, such as optogenetic modulation of strain, are limited to small strain over limited distance and durations. Here, we introduce a high-strain stretcher system, the TissueTractor, designed for high-resolution spatiotemporal imaging of live tissues, enabling strain application varying from 0% to over 150%. This system is needed to unravel the intricate connections between mechanical forces and developmental processes. We demonstrated the stretcher with Xenopus laevis organotypic explants, human umbilical endothelial cells, and mouse neonatal cardiomyocytes to highlight the stretcher's adaptability. These demonstrations underscore the potential of this stretcher to deepen our understanding of the mechanical cues governing tissue dynamics and morphogenesis.

Background: Patients with heart failure and a non-left bundle branch block (non-LBBB) QRS pattern have a limited response to biventricular pacing (BVP)., Objective: A personalized cardiac resynchronization therapy (CRT) implantation approach guided by real-time electrocardiographic imaging (ECGi) was studied., Methods: Twenty patients with left ventricular ejection fraction (LVEF) ≤ 35%, QRS duration ≥ 120 ms, and non-LBBB [13 (65%) with right bundle branch block and 7 (35%) with intraventricular conduction delay] were recruited. During CRT implantation, right atrial, right ventricular, coronary sinus, His-bundle, and/or left bundle leads were inserted. The total activation time (TAT) with different pacing combinations were measured in real time during implantation by ECGi. The configuration producing the shortest TAT was chosen. Clinical response was defined as ≥1 New York Heart Association class improvement. Echocardiographic response was defined as left ventricular end-systolic volume reduction ≥ 15% and/or LVEF improvement ≥ 10% at 6 months., Results: After ECGi-guided CRT implantation, LVEF improved from 26% ± 6% to 34% ± 11% (P < .01) and New York Heart Association class improved from 3.0 ± 0.5 to 2.0 ± 0.6 (P < .01). Both clinical and echocardiographic response rates were 70%. The ECGi approach resulted in better acute electrical resynchronization over BVP as measured by TAT reduction (40% vs 14%; P < .01). The percentage of TAT reduction was found to be a strong predictor for echocardiographic response (area under the curve for the receiver operating characteristic curve 0.91; 95% confidence interval 0.78-1.00). A strong positive correlation between percentage TAT reduction and percentage LVEF improvement (Pearson R = 0.70; P = .001) was found., Conclusion: ECGi-guided CRT implantation in patients with non-LBBB generates superior acute electrical resynchronization compared with BVP and is associated with favorable clinical and echocardiographic outcomes., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Renal tubules have robust active transport and mitochondrial metabolism, which are functionally coupled to maintain energy homeostasis. Here, I review the current literature and our recent efforts to examine mitochondrial adaptation to different transport activities in renal tubules., Recent Findings: The advance of extracellular flux analysis (EFA) allows real-time assessments of mitochondrial respiration, glycolysis, and oxidation of energy substrates. We applied EFA assays to freshly isolated mouse proximal tubules, thick ascending limbs (TALs), and distal convoluted tubules (DCTs) and successfully differentiated their unique metabolic features. We found that TALs and DCTs adjusted their mitochondrial bioenergetics and biogenesis in response to acute and chronic alterations of transport activity. Based on the literature and our recent findings, I discuss working models and mechanisms underlying acute and chronic tubular adaptations to transport activity. The potential roles of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), AMP-activated protein kinase (AMPK), and uncoupling protein 2 (UCP2) are discussed., Summary: Mitochondria in renal tubules are highly plastic to accommodate different transport activities. Understanding the mechanisms may improve the treatment of renal tubulopathies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present 3 cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB (formerly MKL2) gene fusion. Three tumors occurred in 1 male and 2 female patients with a median age of 72 years (range: 28-78). Tumors involved the left iliac bone, the right thigh, and the left perianal region with a median size of 4.0 cm (4.0-7.6 cm). Although 1 tumor presented as an incidental finding, the other 2 tumors were noted, given their persistent growth. At the time of the last follow-up, 1 patient was alive with unresected disease at 6 months, 1 patient was alive without evidence of disease at 12 months after surgery, and 1 patient died of disease 24 months after diagnosis. On histologic sections, the tumors showed multinodular growth and were composed of variably cellular spindle to round-shaped cells with distinct brightly eosinophilic cytoplasm embedded within a myxoid stroma. One tumor showed overt smooth muscle differentiation. Cytologic atypia and mitotic activity ranged from minimal (2 cases) to high (1 case). By immunohistochemistry, the neoplastic cells expressed focal smooth muscle actin, h-caldesmon, and desmin in all tested cases. Skeletal muscle markers were negative. Next-generation sequencing detected nearly identical CRTC1::MRTFB gene fusions in all cases. We suggest that myxoid mesenchymal tumors with myogenic differentiation harboring a CRTC1::MRTFB fusion may represent a previously unrecognized, distinctive entity that involves soft tissue and bone. Continued identification of these novel myxoid neoplasms with myogenic differentiation will be important in determining appropriate classification, understanding biologic potential, and creating treatment paradigms., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Self-improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self-improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self-improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases., (© 2024 The Wound Healing Society.)

Background: The robustness and sensitivity of the surface-enhanced Raman spectroscopy (SERS) technique heavily relies on the development of SERS active materials. A hybrid of semiconductor and plasmonic metals is highly effective as a SERS substrate, which enables the trace level detection of various organic pollutants., Results: This approach demonstrates the photodeposition of plasmonic gold nanoparticles (Au-NPs) on the surface of semiconductor-zinc sulfide nanoflowers (ZnS NFs), grown via the hydrothermal route. The synergistic contribution of the charge-transfer phenomenon and localized surface plasmon resonance of the Au-NPs/ZnS NFs makes it an ideal SERS substrate for the detection of organic pollutants, toluidine blue (TB). The proposed material has a high SERS enhancement factor (10 9 ), low limit of detection (10 -11  M), good reproducibility, selectivity and strong anti-interference ability. Furthermore, the practicability of the Au-NPs/ZnS NFs is explored in real-time water samples, which are obtained with the satisfactory recovery rates. Additionally, the UVC light illumination on the Au-NPs/ZnS NFs has efficiently degraded TB within a time period of 150 min., Significance and Novelty: These finding demonstrate the significance of the proposed Au-NPs/ZnS NFs for SERS based detection and degradation of organic pollutants in real-time samples, highlighting their potential in monitoring and treating water pollutants in wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Metastasis contributes to the increased mortality rate of cancer, but the intricate mechanisms remain unclear. Cancer cells from a primary tumor invade nearby tissues and access the lymphatic or circulatory system. If these cells manage to survive and extravasate from the vasculature into distant tissues and ultimately adapt to survive, they will proliferate and facilitate malignant tumor formation. Traditional two-dimensional (2D) cell cultures offer a rapid and convenient method for validating the efficacy of anticancer drugs within a reasonable cost range, but their utility is limited because of tumors' high heterogeneity in vivo and spatial complexities. Three-dimensional (3D) cell cultures that mimic the physiological conditions of cancer cells in vivo have gained considerable interest. In these cultures, cells assemble into spheroids through gravity, magnetic forces, or their low-adhesion to the plates. Although these approaches address some of the limitations of 2D cultures, they often require a considerable amount of time and cost. Therefore, this study aims to enhance the effectiveness of 3D culture techniques by using microfluidic systems to provide a high-throughput and sensitive pipeline for drug screening. Using these systems, we studied the effects of lanthanide elements, which have garnered interest in cancer treatment, on spheroid formation and cell spreading. Our findings suggest that these elements alter the compactness of cell spheroids and decrease cell mobility., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kai-Yin Lo reports financial support was provided by National Science and Technology Council of Taiwan. Kai-Yin Lo reports financial support was provided by National Taiwan University Hospital. Ya-Wen Yang reports financial support was provided by National Taiwan University Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Development of the cerebellum requires precise regulation of granule neuron progenitor (GNP) proliferation. Although it is known that primary cilia are necessary to support GNP proliferation, the exact molecular mechanism governing primary cilia dynamics within GNPs remains elusive. Here, we establish the pivotal roles for the centrosomal kinase TTBK2 (Tau tubulin kinase-2) and the E3 ubiquitin ligase HUWE1 in GNP proliferation. We show that TTBK2 is highly expressed in proliferating GNPs under Sonic Hedgehog (SHH) signaling, coinciding with active GNP proliferation and the presence of primary cilia. TTBK2 stabilizes primary cilia by inhibiting their disassembly, thereby promoting GNP proliferation in response to SHH. Mechanistically, we identify HUWE1 as a novel centrosomal E3 ligase that facilitates primary cilia disassembly by targeting TTBK2 degradation. Disassembly of primary cilia serves as a trigger for GNP differentiation, allowing their migration from the external granule layer (EGL) of the cerebellum to the internal granule layer (IGL) for subsequent maturation. Moreover, we have established a link between TTBK2 and SHH-type medulloblastoma (SHH-MB), a tumor characterized by uncontrolled GNP proliferation. TTBK2 depletion inhibits SHH-MB proliferation, indicating that TTBK2 may be a potential therapeutic target for this cancer type. In summary, our findings reveal the mechanism governing cerebellar development and highlight a potential anti-cancer strategy for SHH-MB., (© 2024. The Author(s).)

Background: Development of flexible platform via the surface-enhanced Raman spectroscopy (SERS) technique has gained enormous attention as a low-cost and portable substrate for a wide range application. In particular, the fabrication of semiconductors and tuning their surface morphologies with plasmonic nanoparticles are considered to be a fascinating strategy to create numerous hotspots to yield superior SERS enhancement., Results: This work involved fabricating a flexible SERS active substrate using the carbon fiber cloth (CFC), which is hydrothermally grown with cobalt oxide nanowires (Co 3 O 4 NWs) and photodecorated with plasmonic gold nanoparticles (Au-NPs) for the ultrasensitive detection of organic dye, methylene blue (MB). The proposed substrate exhibits high enhancement factor (4.5 × 10 10 ), low limit of detection (1.42 × 10 -10  M), good uniformity (6.27 %), superior reproducibility (6.30 %) and demonstrate an excellent mechanical strength up to 40 cycles towards the MB detection. The residues of the MB are directly detected on the fish surfaces by adopting a facile swab-sampling technique. Additionally, the proposed flexible SERS sensor exhibit a successful photodegradation of MB at 90 min under UVC light irradiation., Significance and Novelty: The proposed flexible SERS methodology for detecting MB in the curved surfaces exhibited a superior SERS enhancement owing to the synergistic effect raised from the Co 3 O 4 NWs (chemical enhancement) and Au NPs (electromagnetic enhancement). These findings indicate that the CFC-based flexible SERS sensor is a promising candidate for detecting various organic pollutants in real-time and on non-planar surfaces., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives : Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used with an increased risk of intracranial hemorrhage. In this nested case-control study, we used Taiwan's nationwide universal health insurance database to investigate the possible association between statin therapy prescribed to acute ischemic stroke patients and their risk of subsequent intracerebral hemorrhage and all-cause mortality in Taiwan. Materials and Methods : All data were retrospectively obtained from Taiwan's National Health Insurance Research Database. Acute ischemic stroke patients were divided into a cohort receiving statin pharmacotherapy and a control cohort not receiving statin pharmacotherapy. A 1:1 matching for age, gender, and index day, and propensity score matching was conducted, producing 39,366 cases and 39,366 controls. The primary outcomes were long-term subsequent intracerebral hemorrhage and all-cause mortality. The competing risk between subsequent intracerebral hemorrhage and all-cause mortality was estimated using the Fine and Gray regression hazards model. Results : Patients receiving statin pharmacotherapy after an acute ischemic stroke had a significantly lower risk of subsequent intracerebral hemorrhage ( p < 0.0001) and lower all-cause mortality rates ( p < 0.0001). Low, moderate, and high dosages of statin were associated with significantly decreased risks for subsequent intracerebral hemorrhage (adjusted sHRs 0.82, 0.74, 0.53) and all-cause mortality (adjusted sHRs 0.75, 0.74, 0.74), respectively. Conclusions : Statin pharmacotherapy was found to safely and effectively reduce the risk of subsequent intracerebral hemorrhage and all-cause mortality in acute ischemic stroke patients in Taiwan.

In this paper, we have developed a 2D optical scanning module comprising cascaded 3D-printed one-axis rotating mirrors with large areas (30×30 m m 2 for the X-direction scan and 60×25 m m 2 for the Y-direction scan). Each mirror device contains a square or rectangular silicon substrate coated with aluminum, serving as the mirror. A 3D-printed structure, including the mirror frame (with four embedded mini permanent magnets on the backside), torsion springs, and base, is combined with the mirror; two electromagnets are situated under the mirror as the actuation mechanism. We apply DC voltage to the electromagnets to create magnetic force. The electromagnets can interact with the permanent magnets to make the mirror rotate. The X scan of the 2D scanning module can achieve a static optical scan angle of ∼11.8 deg at the -X corners, and the corresponding Y-scan angle is ∼4.5 deg , both with 12 VDC. Moreover, we have observed a fan-shaped distortion, a phenomenon not thoroughly studied previously for combining two single-axis scan mirrors. Therefore, we also perform a simulation to establish and demonstrate a correlation between the simulation prediction and experimental results. The 2D scanning module can be a low-cost alternative to the expensive conventional galvanometer scanners, and it can be used to upgrade a rangefinder to a simplified LiDAR.