Detection of freezing of gait in Parkinson's disease from foot-pressure sensing insoles using a temporal convolutional neural network.

Backgrounds: Freezing of gait (FoG) is a common and debilitating symptom of Parkinson's disease (PD) that can lead to falls and reduced quality of life. Wearable sensors have been used to detect FoG, but current methods have limitations in accuracy and practicality. In this paper, we aimed to develop a deep learning model using pressure sensor data from wearable insoles to accurately detect FoG in PD patients. Methods: We recruited 14 PD patients and collected data from multiple trials of a standardized walking test using the Pedar insole system. We proposed temporal convolutional neural network (TCNN) and applied rigorous data filtering and selective participant inclusion criteria to ensure the integrity of the dataset. We mapped the sensor data to a structured matrix and normalized it for input into our TCNN. We used a train-test split to evaluate the performance of the model. Results: We found that TCNN model achieved the highest accuracy, precision, sensitivity, specificity, and F1 score for FoG detection compared to other models. The TCNN model also showed good performance in detecting FoG episodes, even in various types of sensor noise situations. Conclusions: We demonstrated the potential of using wearable pressure sensors and machine learning models for FoG detection in PD patients. The TCNN model showed promising results and could be used in future studies to develop a real-time FoG detection system to improve PD patients' safety and quality of life. Additionally, our noise impact analysis identifies critical sensor locations, suggesting potential for reducing sensor numbers.

Structural Modification and Characteristics of Lappaconitine Alkaloid for the Discovery of Bioactive Components by Hypervalent Iodine Reagent.

Lappaconitine, a diterpene alkaloid isolated from Aconitum sinomontanum Nakai, exhibits a wide range of biological activities, making it a promising candidate for the development of novel derivatives with therapeutic potential. In our research, we executed a two-step transformation via oxidative cleavage of lappaconitine's vicinal diol using the hypervalent iodine reagent PhI(OAc)2, followed by strong alkaline hydrolysis. This approach yielded four new unanticipated compounds, whose structures were identified by spectroscopic methods and/or X-ray crystallography. Thus, we proposed plausible reaction mechanisms for their formations and particularly investigated the remarkable diastereoselectivity for the formation of single stereoisomer 8 observed during the alkaline hydrolysis step. Among them, compound 8 (code name: QG3030) demonstrated both enhanced osteogenic differentiation of human mesenchymal stem cells and significant osteogenic effect in an ovariectomized rat model with no acute oral toxicity.

Extracellular vesicle isolation and counting system (EVics) based on simultaneous tandem tangential flow filtration and large field-of-view light scattering.

Although the isolation and counting of small extracellular vesicles (sEVs) are essential steps in sEV research, an integrated method with scalability and efficiency has not been developed. Here, we present a scalable and ready-to-use extracellular vesicle (EV) isolation and counting system (EVics) that simultaneously allows isolation and counting in one system. This novel system consists of (i) EVi, a simultaneous tandem tangential flow filtration (TFF)-based EV isolation component by applying two different pore-size TFF filters, and (ii) EVc, an EV counting component using light scattering that captures a large field-of-view (FOV). EVi efficiently isolated 50-200 nm-size sEVs from 15 µL to 2 L samples, outperforming the current state-of-the-art devices in purity and speed. EVc with a large FOV efficiently counted isolated sEVs. EVics enabled early observations of sEV secretion in various cell lines and reduced the cost of evaluating the inhibitory effect of sEV inhibitors by 20-fold. Using EVics, sEVs concentrations and sEV PD-L1 were monitored in a 23-day cancer mouse model, and 160 clinical samples were prepared and successfully applied to diagnosis. These results demonstrate that EVics could become an innovative system for novel findings in basic and applied studies in sEV research.

Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Background/Aims: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Methods: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. Results: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Conclusions: Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

A survey of current practices in post-polypectomy surveillance in Korea.

BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

Surgical Correction of a Sinus Venosus Atrial Septal Defect with Partial Anomalous Pulmonary Venous Connections Using Cardiac Computed Tomography Imaging and a 3D-Printed Model.

Sinus venosus atrial septal defects (SVASDs), concurrent with partial anomalous pulmonary venous connections (PAPVCs), are a rare congenital heart disease in dogs. Surgical correction is essential when clinical signs or significant hemodynamic changes are present. We aimed to report on the successful surgical correction of an SVASD with PAPVCs, using a computed tomography (CT)-based customized 3D cardiac model. A 10-month-old male poodle was referred for corrective surgery for an ASD. Echocardiography confirmed a hemodynamically significant left-to-right shunting flow through an interatrial septal defect and severe right-sided heart volume overload. For a comprehensive diagnosis, a CT scan was performed, which confirmed an SVASD with PAPVCs. A customized 3D cardiac model was used for preoperative decision-making and surgical rehearsal. The defect was repaired using an autologous pericardial patch under a cardiopulmonary bypass (CPB). Temporary pacing was applied for sinus bradycardia and third-degree atrioventricular block. The patient recovered from the anesthesia without further complications. The pacemaker was removed during hospitalization and the patient was discharged without complications 2 weeks post-surgery. At the three-month follow-up, there was no shunting flow in the interatrial septum and the right-sided volume overload had been resolved. The cardiac medications were discontinued, and there were no complications. This report indicates the validity of surgical correction under CPB for an SVASD with PAPVCs, and the advantages of utilizing a CT-based 3D cardiac model for preoperative planning to increase the surgical success rate.

Association between low-dose aspirin and the risk of gastric cancer and adenoma according to a family history of gastric cancer.

This study aimed to evaluate the association between low-dose aspirin use and the risk of GC and gastric adenoma according to a family history of GC. We conducted a population-based study of 7,596,003 participants screened for GC between 2013 and 2014. Aspirin users and non-users were matched in a 1:1 ratio through propensity score matching (PSM). After PSM, 51,818 participants with a family history of GC and 359,840 without a family history of GC were analyzed (mean follow-up periods: 4.9 ± 0.8 and 4.8 ± 0.8 years, respectively). In patients with a family history of GC, aspirin use was significantly associated with a reduced risk of GC (adjusted hazard ratio [aHR]=0.80; 95 % confidence interval [CI]=0.65-0.995) and gastric adenoma (aHR=0.81; 95% CI=0.69-0.94). In those without a family history of GC, aspirin use was associated with a reduced risk of gastric adenoma (aHR = 0.92; 95 % CI = 0.86-0.98), but not with that of GC (aHR = 0.99; 95 % CI = 0.90-1.08). Low-dose aspirin use was associated with a reduced risk of gastric adenoma, regardless of a family history of GC, and may play a role in the early stages of gastric carcinogenesis. However, the association between aspirin and GC was only observed in those with a family history of GC.

Feasibility of Mobile Health App-Based Home Aerobic Exercise for Physical Performance in Healthy Young Adults.

OBJECTIVE: To investigate the feasibility and effects of a mobile app-based home cycling exercise program compared to home cycling exercise without additional monitoring system. Compared with fitness facilities or outdoor exercise, home-based exercise programs effectively improve physical performance in an indwelling community. However, a flexible, informal environment may decrease motivation and impair adherence to physical exercise. Mobile devices for aerobic exercise and mobile applications provide real-time monitoring, immediate feedback, and encouragement to increase motivation and promote physical performance. We investigated the feasibility and effects of a mobile app-based home exercise program on body composition, muscular strength, and cardiopulmonary function. METHODS: Between February and May 2023, 20 participants were randomly allocated to the intervention (mobile application with a tablet) and control groups, and they performed aerobic exercise using a stationary bicycle for ≥150 minutes per week for 6 weeks (≤30-minute exercise session, with 3-minute warm-up and 3-minute cool-down). Karvonen formula-based heartrate defined the weekly increase in exercise intensity. Outcome measures included body-composition parameters, isokinetic knee flexor and extensor strength tests, cardiopulmonary exercise test results, and rate of target heart rate (HR) achievement. Participants were assessed at baseline and after the intervention. RESULTS: Unrelated personal events led two participants to drop out. The intervention and control groups had similar baseline characteristics. Compared with the control group, in the post-intervention isokinetic strength test, bilateral knee flexor and extensor power, and time to target HR achievement significantly increased each week in the intervention group. CONCLUSION: Home-based exercise to achieve long-term cardiovascular fitness with portable electronic/mobile devices facilitates individualized exercise using real-time feedback to improve motivation and adherence.

Effects of resistance training and nutritional support on osteosarcopenia in older, community-dwelling postmenopausal Korean females (ERTO-K study): a study protocol.

BACKGROUND: Osteosarcopenia is geriatric syndrome defined as the concomitant occurrence of osteopenia/osteoporosis, and sarcopenia. Osteosarcopenia is a relatively new concept in geriatric medicine; however, it may increase the risk of fragility fractures, several morbidities and mortalities, and socioeconomic costs. Although resistance exercises and nutritional support-including protein, calcium, and vitamin D-are potential non-pharmacological management procedures, evidence is still lacking. The objective of this study was therefore to evaluate the effect of combined resistance exercise and nutritional support on the quality and quantity of bone and muscle in postmenopausal females with osteosarcopenia. METHODS: This research proposal presents the protocol for a prospective, single-center, single-blinded, two-armed randomized controlled trial. Thirty-four participants with osteosarcopenia will be recruited and randomly divided into intervention and control groups; both groups will receive nutritional supplements (protein, 40 g; vitamin D, 1600 IU; calcium, 600 mg) daily. The intervention group will undergo 24 weeks of resistance exercise of increasing intensity, achieved through a three-phase step-up process. The primary outcomes will be the changes in skeletal muscle index and bone marrow density of the lumbar spine and femoral neck between the baseline and end of intervention (24 weeks). The secondary outcomes will be the body composition, whole body phase angle, physical function assessment, quality of life, psychological assessment, and bone turnover markers of participants, surveyed at multiple time points. DISCUSSION: This randomized controlled trial may reveal the effect of resistance exercise and nutritional support on older postmenopausal women with osteosarcopenia. The results will provide evidence for developing proper non-pharmacological management guidelines for postmenopausal women. TRIAL REGISTRATION: Clinical Research Information Service of Republic of Korea, KCT0008291, Registered on 16 March 2023, https://cris.nih.go.kr/cris/search/detailSearch.do/25262 .

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea.

BACKGROUND: The incidence of colorectal cancer (CRC) and preinvasive CRC (e.g., early colon cancer and advanced adenoma) is gradually increasing in several countries. AIM: To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea. METHODS: This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC, and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies. Colonoscopy-related complications by age group were also determined. RESULTS: The incidence of CRC showed a rapid increase, then decreased after 2012 in the 50-75 year-age group. During the study period, the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age. Since 2009, the increase has been rapid, showing a pattern similar to the increase in colonoscopies. The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007. The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age. CONCLUSION: The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed. As the risk of colonoscopy-related hospitalization and death is high in the elderly, if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75, colonoscopy-related complications can be reduced for those aged 76 years or over.

Intense pulsed light annealing of solution-based indium-gallium-zinc-oxide semiconductors with printed Ag source and drain electrodes for bottom gate thin film transistors.

In this study, an intense pulsed light (IPL) annealing process for a printed multi-layered indium-gallium-zinc-oxide (IGZO) and silver (Ag) electrode structure was developed for a high performance all-printed inorganic thin film transistor (TFT). Through a solution process using IGZO precursor and Ag ink, the bottom gate structure TFT was fabricated. The spin coating method was used to form the IGZO semiconductor layer on a heavily-doped silicon wafer covered with thermally grown silicon dioxide. The annealing process of the IGZO layer utilized an optimized IPL irradiation process. The Ag inks were printed on the IGZO layer by screen printing to form the source and drain (S/D) pattern. This S/D pattern was dried by near infrared radiation (NIR) and the dried S/D pattern was sintered with intense pulsed light by varying the irradiation energy. The performances of the all-printed TFT such as the field effect mobility and on-off ratio electrical transfer properties were measured by a parameter analyzer. The interfacial analysis including the contact resistance and cross-sectional microstructure analysis is essential because diffusion phenomenon can occur during the annealing and sintering process. Consequently, this TFT device showed noteworthy performance (field effect mobility: 7.96 cm2/V s, on/off ratio: 107). This is similar performance compared to a conventional TFT, which is expected to open a new path in the printed metal oxide-based TFT field.

Cathepsin D promotes polarization of tumor-associated macrophages and metastasis through TGFBI-CCL20 signaling.

M2-like tumor-associated macrophages (TAMs) are risk factors for cancer progression and metastasis. However, the mechanisms underlying their polarization are still not fully understood. Although cathepsin D (Cat D) has been reported as a procarcinogenic factor, little is known about the functional role of Cat D in the tumor microenvironment (TME). This study aimed to explore the effect and molecular mechanisms of Cat D in the TME. Cat D knockout (KO) altered the cytokine secretion pattern and induced TAM reprogramming from the M2 to M1 subtype, thereby preventing epithelial-mesenchymal transition and tumor metastasis. Mechanistically, we identified transforming growth factor beta-induced protein (TGFBI) as a Cat D target protein that is specifically associated with TAM polarization. Elevated TGFBI expression in Cat D KO cancer cells resulted in a decline in M2-like TAM polarization. Our RNA-sequencing results indicated that the cancer cell-secreted chemokine CCL20 is a major secretory chemokine for Cat D-TGFBI-mediated TAM polarization. In contrast, Cat D overexpression accelerated TAM polarization into M2-like cells by suppressing TGFBI expression. In addition, the double Cat D and TGFBI KO rescued the inhibitory effects of Cat D KO on tumor metastasis by controlling TAM and T-cell activation. These findings indicated that Cat D contributes to cancer metastasis through TGFBI-mediated TAM reprogramming. Cat D deletion inhibits M2-like TAM polarization through TGFBI-mediated CCL20 expression, reprogramming the immunosuppressive TME. Our results open a potential new avenue for therapy focused on eliminating tumor metastasis.

Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: current advances and therapeutic applications.

Cancer immunotherapy has revolutionized the approach to cancer treatment of malignant tumors by harnessing the body's immune system to selectively target cancer cells. Despite remarkable advances, there are still challenges in achieving successful clinical responses. Recent evidence suggests that immune cell-derived exosomes modulate the immune system to generate effective antitumor immune responses, making them a cutting-edge therapeutic strategy. However, natural exosomes are limited in clinical application due to their low drug delivery efficiency and insufficient antitumor capacity. Technological advancements have allowed exosome modifications to magnify their intrinsic functions, load different therapeutic cargoes, and preferentially target tumor sites. These engineered exosomes exert potent antitumor effects and have great potential for cancer immunotherapy. In this review, we describe ingenious modification strategies to attain the desired performance. Moreover, we systematically summarize the tumor-controlling properties of engineered immune cell-derived exosomes in innate and adaptive immunity. Collectively, this review provides a comprehensive and intuitive guide for harnessing the potential of modified immune cell-derived exosome-based approaches, offering valuable strategies to enhance and optimize cancer immunotherapy.

ClinicalOmicsDB: exploring molecular associations of oncology drug responses in clinical trials.

Matching patients to optimal treatment is challenging, in part due to the limited availability of real-world clinical datasets for predictive biomarker identification. The growing integration of omics profiling into clinical trials presents a new opportunity to tackle this challenge. Here, we introduce ClinicalOmicsDB, a web application for exploring molecular associations of oncology drug responses in clinical trials. This database includes transcriptomic data from 40 clinical trial studies, with 5913 patients spanning 11 cancer types. These studies include 67 treatment arms with a variety of chemotherapy, targeted therapy and immunotherapy drugs, and their combinations, which we organize based on an established ontology for easier navigation. The web application provides users with three options to explore molecular associations of oncology drug responses, focusing on studies, treatments or genes, respectively. Gene set analysis further connects treatment response to pathway activity and tumor microenvironment attributes. The user-friendly web interface of ClinicalOmicsDB streamlines interactive analysis. A Rust-based backend speeds up response time, and application programming interfaces and an R package enable programmatic access. We use three case studies to demonstrate the utility of this resource in human cancer studies. ClinicalOmicsDB is freely available at http://trials.linkedomics.org/.

Drug Responses in Plexiform Neurofibroma Type I (PNF1) Cell Lines Using High-Throughput Data and Combined Effectiveness and Potency.

Background: Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by heterozygous germline NF1 gene mutations that predispose patients to developing plexiform neurofibromas, which are benign but often disfiguring tumors of the peripheral nerve sheath induced by loss of heterozygosity at the NF1 locus. These can progress to malignant peripheral nerve sheath tumors (MPNSTs). There are no approved drug treatments for adults with NF1-related inoperable plexiform neurofibromas, and only one drug (selumetinib), which is an FDA-approved targeted therapy for the treatment of symptomatic pediatric plexiform neurofibromas, highlighting the need for additional drug screening and development. In high-throughput screening, the effectiveness of drugs against cell lines is often assessed by measuring in vitro potency (AC50) or the area under the curve (AUC). However, the variability of dose-response curves across drugs and cell lines and the frequency of partial effectiveness suggest that these measures alone fail to provide a full picture of overall efficacy. Methods: Using concentration-response data, we combined response effectiveness (EFF) and potency (AC50) into (a) a score characterizing the effect of a compound on a single cell line, S = log[EFF/AC50], and (b) a relative score, ΔS, characterizing the relative difference between a reference (e.g., non-tumor) and test (tumor) cell line. ΔS was applied to data from high-throughput screening (HTS) of a drug panel tested on NF1-/- tumor cells, using immortalized non-tumor NF1+/- cells as a reference. Results: We identified drugs with sensitivity, targeting expected pathways, such as MAPK-ERK and PI3K-AKT, as well as serotonin-related targets, among others. The ΔS technique used here, in tandem with a supplemental ΔS web tool, simplifies HTS analysis and may provide a springboard for further investigations into drug response in NF1-related cancers. The tool may also prove useful for drug development in a variety of other cancers.

Development of functional gastrointestinal disorder symptoms following laparoscopic cholecystectomy: a prospective cohort study.

Background: The casual relationship between the role of cholecystectomy and functional gastrointestinal disorders (FGIDs) are a controversial clinical challenge. This study aimed to investigate: (1) the overlap of FGIDs before cholecystectomy and its long-term outcome after surgery in patients with symptomatic cholelithiasis, and (2) the incidence of new-onset FGIDs after cholecystectomy. Methods: Patients with symptomatic gallstone disease who underwent elective, laparoscopic cholecystectomy were prospectively enrolled. Healthy populations who underwent medical check-ups were selected as age- and sex-matched controls. Questionnaires regarding sociodemographic characteristics, gastrointestinal symptoms and a somatization symptom checklist (SSC) were completed at baseline and 12 months thereafter. Results: The prevalence of all FGID symptoms before cholecystectomy were significantly higher in the group of patients with symptomatic cholecystolithiasis compared to the control group. In cholecystectomy group, the preoperative FGID symptoms improved after surgery, except for chronic diarrhea. Compared to the controls, the new-onset FGIDs, including functional dyspepsia (14.8% vs. 6.9%; p = 0.040), functional diarrhea (6.6% vs. 0.2%; p < 0.001), and chronic abdominal pain (11.9% vs. 4.4%; p = 0.024), were more common at 1 year after cholecystectomy. Somatization was independent predictors of new-onset dyspepsia and abdominal pain, while newly occurring diarrhea was not realted to somatization. Conclusion: Overlap of FGIDs was common in patients with symptomatic cholelithiasis before surgery and at follow-up 1 year after cholecystectomy. Furthermore, new-onset FGIDs could be occurred after cholecystectomy. Therefore, a delicate diagnostic approaches and appropriate treatments about co-existent FGIDs should be given in patients with cholelithiasis before and after cholecystectomy.

Ellagic Acid Prevented Dextran-Sodium-Sulfate-Induced Colitis, Liver, and Brain Injury through Gut Microbiome Changes.

Inflammatory bowel disease (IBD) affects millions of people worldwide and is considered a significant risk factor for colorectal cancer. Recent in vivo and in vitro studies reported that ellagic acid (EA) exhibits important antioxidant and anti-inflammatory properties. In this study, we investigated the preventive effects of EA against dextran sulfate sodium (DSS)-induced acute colitis, liver, and brain injury in mice through the gut-liver-brain axis. Acute colitis, liver, and brain injury were induced by treatment with 5% (w/v) DSS in the drinking water for 7 days. Freshly prepared EA (60 mg/kg/day) was orally administered, while control (CON) group mice were treated similarly by daily oral administrations with a vehicle (water). All the mice were euthanized 24 h after the final treatment with EA. The blood, liver, colon, and brain samples were collected for further histological and biochemical analyses. Co-treatment with a physiologically relevant dose (60 mg/kg/day) of EA for 7 days significantly reduced the DSS-induced gut barrier dysfunction; endotoxemia; and inflammatory gut, liver, and brain injury in mice by modulating gut microbiota composition and inhibiting the elevated oxidative and nitrative stress marker proteins. Our results further demonstrated that the preventive effect of EA on the DSS-induced IBD mouse model was mediated by blocking the NF-κB and mitogen-activated protein kinase (MAPK) pathway. Therefore, EA co-treatment significantly attenuated the pro-inflammatory and oxidative stress markers by suppressing the activation of NF-κB/MAPK pathways in gut, liver, and brain injury. These results suggest that EA, effective in attenuating IBD in a mouse model, deserves further consideration as a potential therapeutic for the treatment of inflammatory diseases.

Targeting the multidrug and toxin extrusion 1 gene (SLC47A1) sensitizes glioma stem cells to temozolomide.

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, with an extremely poor prognosis due to resistance to standard-of-care treatments. Strong evidence suggests that the small population of glioma stem cells (GSCs) contributes to the aggressiveness of GBM. One of the mechanisms that promote GSC progression is the dysregulation of membrane transporters, which mediate the influx and efflux of substances to maintain cellular homeostasis. Here, we investigated the role of multidrug and toxin extrusion transporter gene SLC47A1 in GSCs. Results show that SLC47A1 is highly expressed in GSCs compared to non-stem cell glioma cells, and non-tumor cells. Additionally, in-silico analysis of public datasets showed that high SLC47A1 expression is linked to malignancy and a poor prognosis in glioma patients. Further, SLC47A1 expression is correlated with important biological processes and signaling pathways that support tumor growth. Meanwhile, silencing SLC47A1 by short-hairpin RNA (shRNA) influenced cell viability and self-renewal activity in GSCs. Interestingly, SLC47A1 shRNA knockdown or pharmacological inhibition potentiates the effect of temozolomide (TMZ) in GSC cells. The findings suggest that SLC47A1 could serve as a useful therapeutic target for gliomas.

Partial Venous Inflow Occlusion under Mild Hypothermia for Membranectomy in a Dog with Cor Triatriatum Dexter.

Cor triatriatum dexter (CTD) is an uncommon congenital cardiac anomaly in dogs. This case report describes successful membranectomy for CTD via partial venous inflow occlusion under mild hypothermia in a dog. A 7-month-old intact male mixed-breed dog weighing 20.5 kg presented with a history of abdominal distention, lethargy, and anorexia. Clinical examination, radiography, echocardiography, microbubble testing, and computed tomography revealed a remnant right atrium membrane obscuring the venous blood inflow from the vena cava. Considering the potential risk of re-stenosis following interventional treatment, curative resection involving surgical membranectomy via venous inflow occlusion was performed. By performing partial venous inflow occlusion under mild hypothermia (34.5 °C), sufficient time was obtained to explore the defect and resect the remnant membrane. The dog recovered without any complications, and the clinical signs were relieved. This case illustrates that partial venous inflow occlusion under mild hypothermia is feasible for achieving curative resection of cor triatriatum dexter in dogs.

High-Density Integration of Ultrabright OLEDs on a Miniaturized Needle-Shaped CMOS Backplane.

Direct deposition of organic light-emitting diodes (OLEDs) on silicon-based complementary metal-oxide-semiconductor (CMOS) chips has enabled self-emissive microdisplays with high resolution and fill-factor. Emerging applications of OLEDs in augmented and virtual reality (AR/VR) displays and in biomedical applications, e.g., as brain implants for cell-specific light delivery in optogenetics, require light intensities orders of magnitude above those found in traditional displays. Further requirements often include a microscopic device footprint, a specific shape and ultrastable passivation, e.g., to ensure biocompatibility and minimal invasiveness of OLED-based implants. In this work, up to 1024 ultrabright, microscopic OLEDs are deposited directly on needle-shaped CMOS chips. Transmission electron microscopy and energy-dispersive X-ray spectroscopy are performed on the foundry-provided aluminum contact pads of the CMOS chips to guide a systematic optimization of the contacts. Plasma treatment and implementation of silver interlayers lead to ohmic contact conditions and thus facilitate direct vacuum deposition of orange- and blue-emitting OLED stacks leading to micrometer-sized pixels on the chips. The electronics in each needle allow each pixel to switch individually. The OLED pixels generate a mean optical power density of 0.25 mW mm-2 , corresponding to >40 000 cd m-2 , well above the requirement for daylight AR applications and optogenetic single-unit activation in the brain.