Neurosonography: Shaping the future of neuroprotection strategies in extremely preterm infants.

This review aims to explore the current application of Cranial Ultrasound Screening (CUS) in the diagnosis and treatment of brain diseases in extremely preterm infants. It also discusses the potential role of emerging ultrasound-derived technologies such as Super Microvascular Structure Imaging (SMI), Shear Wave Elastography (SWE), Ultrafast Doppler Ultrasound (UfD), and 3D ventricular volume assessment and automated segmentation techniques in clinical practice. A systematic search of medical databases was conducted using the keywords "(preterm OR extremely preterm OR extremely low birth weight) AND (ultrasound OR ultrasound imaging) AND (neurodevelopment OR brain development OR brain diseases OR brain injury OR neuro*)" to identify relevant literature. The titles, abstracts, and full texts of the identified articles were carefully reviewed to determine their relevance to the research topic. CUS offers unique advantages in early screening and monitoring of brain diseases in extremely preterm infants, as it can be performed at the bedside without the need for anesthesia or special monitoring. This technique facilitates early detection and intervention of conditions such as intraventricular hemorrhage, white matter injury, hydrocephalus, and hypoxic-ischemic injury in critically ill preterm infants. Continuous refinement of the screening and follow-up processes provides reliable clinical decision-making support for healthcare professionals and parents. Emerging ultrasound technologies, such as SWE, SMI, and UfD, are being explored to provide more accurate and in-depth understanding of brain diseases in extremely preterm infants. SWE has demonstrated its effectiveness in assessing the elasticity of neonatal brain tissue, aiding in the localization and quantification of potential brain injuries. SMI can successfully identify microvascular structures in the brain, offering a new perspective on neurologic diseases. UfD provides a high-sensitivity and quantitative imaging method for the prevention and treatment of neonatal brain diseases by detecting subtle changes in red blood cell movement and accurately assessing the status and progression of brain diseases. CUS and its emerging technologies have significant applications in the diagnosis and treatment of brain diseases in extremely preterm infants. Future research aims to address current technical challenges, optimize and enhance the clinical decision-making capabilities related to brain development, and improve the prevention and treatment outcomes of brain diseases in extremely preterm infants.

Mycolicibacterium arseniciresistens sp. nov., isolated from lead-zinc mine tailing, and reclassification of two Mycobacterium species as Mycolicibacterium palauense comb. nov. and Mycolicibacterium grossiae comb. nov.

A Gram-positive, acid-fast, aerobic, rapidly growing and non-motile strain was isolated from lead-zinc mine tailing sampled in Lanping, Yunnan province, Southwest China. 16S rRNA gene sequence analysis showed that the most closely related species of strain KC 300T was Mycolicibacterium litorale CGMCC 4.5724T (98.47 %). Additionally, phylogenomic and specific conserved signature indel analysis revealed that strain KC 300T should be a member of genus Mycolicibacterium, and Mycobacterium palauense CECT 8779T and Mycobacterium grossiae DSM 104744T should also members of genus Mycolicibacterium. The genome size of strain KC 300T was 6.2 Mb with an in silico DNA G+C content of 69.2 mol%. Chemotaxonomic characteristics of strain KC 300T were also consistent with the genus Mycolicibacterium. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values, as well as phenotypic, physiological and biochemical characteristics, support that strain KC 300T represents a new species within the genus Mycolicibacterium, for which the name Mycolicibacterium arseniciresistens sp. nov. is proposed, with the type strain KC 300T (=CGMCC 1.19494T=JCM 35915T). In addition, we reclassified Mycobacterium palauense and Mycobacterium grossiae as Mycolicibacterium palauense comb. nov. and Mycolicibacterium grossiae comb. nov., respectively.

Brain development in newborns and infants after ECMO.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) not only significantly improves survival rates in severely ill neonates but also is associated with long-term neurodevelopmental issues. To systematically review the available literature on the neurodevelopmental outcomes of neonates and infants who have undergone ECMO treatment, with a focus on motor deficits, cognitive impairments, sensory impairments, and developmental delays. This review aims to understand the incidence, prevalence, and risk factors for these problems and to explore current nursing care and management strategies. DATA SOURCES: A comprehensive literature search was performed across PubMed, EMBASE, and Web of Science using a wide array of keywords and phrases pertaining to ECMO, neonates, infants, and various facets of neurodevelopment. The initial screening involved reviewing titles and abstracts to exclude irrelevant articles, followed by a full-text assessment of potentially relevant literature. The quality of each study was evaluated based on its research methodology and statistical analysis. Moreover, citation searches were conducted to identify potentially overlooked studies. Although the focus was primarily on neonatal ECMO, studies involving children and adults were also included due to the limited availability of neonate-specific literature. RESULTS: About 50% of neonates post-ECMO treatment exhibit varying degrees of brain injury, particularly in the frontal and temporoparietal white matter regions, often accompanied by neurological complications. Seizures occur in 18%-23% of neonates within the first 24 hours, and bleeding events occur in 27%-60% of ECMO procedures, with up to 33% potentially experiencing ischemic strokes. Although some studies suggest that ECMO may negatively impact hearing and visual development, other studies have found no significant differences; hence, the influence of ECMO remains unclear. In terms of cognitive, language, and intellectual development, ECMO treatment may be associated with potential developmental delays, including lower composite scores in cognitive and motor functions, as well as potential language and learning difficulties. These studies emphasize the importance of early detection and intervention of potential developmental issues in ECMO survivors, possibly necessitating the implementation of a multidisciplinary follow-up plan that includes regular neuromotor and psychological evaluations. Overall, further multicenter, large-sample, long-term follow-up studies are needed to determine the impact of ECMO on these developmental aspects. CONCLUSIONS: The impact of ECMO on an infant's nervous system still requires further investigation with larger sample sizes for validation. Fine-tuned management, comprehensive nursing care, appropriate patient selection, proactive monitoring, nutritional support, and early rehabilitation may potentially contribute to improving the long-term outcomes for these infants.

Age-induced aortic modifications are accompanied by alterations in the antioxidant defense system in female rats.

Introduction: Aging leads to significant structural and functional changes in blood vessels, which disrupt their normal function and impact cardiovascular health. Current research is actively exploring the NRF2 antioxidative pathway, recognizing its role in protecting cells by preserving their antioxidant defenses against damage. However, there has been limited exploration into the role of the NRF2 pathway in vascular aging. The primary objective of this study was to determine whether age-related changes in the aorta are associated with variations in the baseline levels of antioxidant enzymes, with a particular emphasis on how the NRF2 pathway operates in the aortic wall. Methods: A group of healthy aging female SD rats was compared with their younger counterparts. Various assessments were conducted, including measuring blood pressure, analyzing serum lipid profiles, examining aortic tissue, and assessing the expression of antioxidant enzymes. Results: The results revealed significant differences in both blood pressure and serum lipid levels between the aged and younger rats. The examination of the aorta in older rats showed structural alterations, increased apoptosis, and the accumulation of fatty deposits. In the older rats, levels of SOD-1 (superoxide dismutase) and GSS (glutathione synthetase) were lower, whereas NRF2, KEAP-1 (Kelch-like ECH-associated protein 1), and HO-1 (Heme oxygenase 1) were higher. Discussion: This study advances our understanding of how aging affects the antioxidant system in blood vessels, particularly in relation to the regulation of the NRF2/HO-1 pathway in the aorta. These findings suggest that targeting the NRF2/HO-1 pathway could present anovel therapeutic approach for addressing age-related vascular issues.

Association between continuous glucose profile during therapeutic hypothermia and unfavorable outcome in neonates with hypoxic-ischemic encephalopathy209 23-32.

BACKGROUND: The detection and management of blood glucose abnormalities in high-risk neonates are crucial for clinical care. The objective of the study was to investigate the continuous glucose profile of hypoxic-ischemic encephalopathy (HIE) patients in the whole-process of therapeutic hypothermia (TH) and its association with clinical and neurological outcomes. METHOD: In this single-center retrospective study, HIE patients who received both TH and continuous glucose monitoring (CGM) were recruited from March 2016 to September 2021. RESULTS: Of 47 neonates recruited, 24 had unfavorable outcome. Dysglycemia was most prevalent in the first 24 h of TH, among which hyperglycemia occurred more frequently. CGM showed that the duration, episodes and area under curve (AUC) of hypoglycemia were statistically different in neonates with different outcomes. The occurrence, longer duration, greater AUC of hypoglycemia and an early high coefficient of variation (CV%, CV = SD/mean) were associated with unfavorable outcomes (aOR 26.55 [2.02-348.5], aOR 2.11 [1.08-4.14], aOR 1.80 [1.11-2.91] and aOR respectively), while hyperglycemia was not. CONCLUSION: During the whole process of TH, hypoglycemia and early unstable glycemic variability were strongly associated with unfavorable outcomes. CGM can instantly detect dysglycemia and facilitate precise glucose management in HIE neonates.

Dual-Targeting PET Tracers Enable Enzyme-Mediated Self-Assembly for the PET Imaging of Legumain Activity.

Legumain, a lysosomal cysteine protease overexpressed in a variety of tumors, has been considered a promising biomarker for various cancers. Precise detection of legumain activity in the lysosome represents an important strategy for early diagnosis and prognosis of tumors. Small-molecule probes with the property of target-enabled self-assembly hold great potential for molecular imaging. In this study, we reported two dual-targeting radiotracers ([18F]SF-AAN-M and [18F]SF-AAN-HEM) with a property of legumain-mediated self-assembly for positron emission tomography (PET) imaging. Both the radiotracers were synthesized with high labeling yield (>50%) and the radiochemical purity was over 99% via one-step straightforward 18F-labeling. Both tracers were efficiently activated by the reducing agent and legumain to self-assemble into aggregates and showed enhanced retention in legumain-overexpressed MDA-MB-468 cells and tumors, indicating that the introduction of lysosome-targeting morpholine increased the tumor uptake and extended the retention of radiotracers in legumain-overexpressed tumors. In addition, [18F]SF-AAN-HEM with a hydrophilic (histidine-glutamate)3 tag displayed significantly reduced liver uptake with no conspicuous reduction in tumor uptake, affording high signal-to-noise ratios (tumor/liver and tumor/muscle). All of these results suggest that dual-targeting tracer [18F]SF-AAN-HEM could provide a promising tool for in vivo monitoring legumain activity in tumors.

Incidence of Neonatal Seizures in China Based on Electroencephalogram Monitoring in Neonatal Neurocritical Care Units.

Importance: Neonatal seizures pose a significant challenge in critical care, and continuous video electroencephalography (cEEG) monitoring holds promise for early detection of seizures. However, large-scale data on the incidence of neonatal seizures and monitoring systems in China are lacking. Objectives: To determine the incidence of neonatal seizures in infants with high risk in China. Design, Setting, and Participants: A large, cross-sectional multicenter study was conducted from January 2017 to December 2018 in the neonatal intensive care units (NICUs) of 7 tertiary medical centers in China. Neonates with high risk were included, and cEEG monitoring was conducted. Data were collected between January 1, 2017, and January 31, 2020. The data were analyzed between January 2021 and January 2022. Main Outcomes and Measures: The incidence of neonatal seizures, categorized by etiology, and seizure burden. Results: A total of 20 310 neonates with high risk were included (10 495 [51.7%] male; mean [SD] postmenstrual age, 37.7 [3.7] weeks), and seizures were observed in 3423 infants (16.9%). The highest proportion of seizures was attributed to acute neonatal encephalopathy (1448 [42.3%]). The incidence of seizures decreased with postmenstrual age and birth weight, with the highest occurrence observed in neonates with postmenstrual age of less than 28 weeks (237 of 879 [27.0%]) or birth weight of less than 1.0 kg (269 of 914 [29.4%]). Preterm infants had a higher proportion of moderate and severe seizure burdens compared with full-term infants (moderate severity: 248 of 1199 [20.7%] vs 454 of 2224 [20.4%]), but no significant differences were observed in etiology. Seizure burden was highest with genetic syndromes (49 of 188 [26.1%]), central nervous system malformations (33 of 127 [26.0%]), and inborn errors of metabolism (27 of 113 [23.9%]). During hospitalization, 7.8% of neonates with seizures died (267 neonates), with 81.3% of these cases having a moderate or severe seizure burden (217 neonates). Mortality was generally higher in preterm vs full-term infants (98 of 1199 [8.2%] vs 169 of 2224 [7.6%]) and increased with the severity of seizure burden (217 of 267 neonates with moderate or severe burden [81.3%]). Conclusions and Relevance: This cross-sectional study of neonatal seizures underscores the substantial burden seizures pose to high-risk infants with brain injury in China, particularly those who are born prematurely or who have congenital conditions.

Neonatal Seizure Detection Using a Wearable Multi-Sensor System.

Neonatal seizure is an important clinical symptom of brain dysfunction, which is more common in infancy than in childhood. At present, video electroencephalogram (VEEG) technology is widely used in clinical practice. However, video electroencephalogram technology has several disadvantages. For example, the wires connecting the medical instruments may interfere with the infant's movement and the gel patch electrode or disk electrode commonly used to monitor EEG may cause skin allergies or even tears. For the above reasons, we developed a wearable multi-sensor platform for newborns to collect physiological and movement signals. In this study, we designed a second-generation multi-sensor platform and developed an automatic detection algorithm for neonatal seizures based on ECG, respiration and acceleration. Data for 38 neonates were recorded at the Children's Hospital of Fudan University in Shanghai. The total recording time was approximately 300 h. Four of the patients had seizures during data collection. The total recording time for the four patients was approximately 34 h, with 30 seizure episodes recorded. These data were evaluated by the algorithm. To evaluate the effectiveness of combining ECG, respiration and movement, we compared the performance of three types of seizure detectors. The first detector included features from ECG, respiration and acceleration records; the second detector incorporated features based on respiratory movement from respiration and acceleration records; and the third detector used only ECG-based features from ECG records. Our study illustrated that, compared with the detector utilizing individual modal features, multi-modal feature detectors could achieve favorable overall performance, reduce false alarm rates and give higher F-measures.

Examining the effects of student-centered flipped classroom in physiology education.

BACKGROUND: The flipped classroom approach has gained increasing popularity in medical education. Physiology is a basic medical course that studies the phenomena and laws of human life activities, and is a crucial link course connecting preclinical courses and clinical courses. However, there is a paucity of data showing the effectiveness of the flipped classroom model for the entirety of physiology course in medical undergraduate students. METHOD: 131 sophomore students with clinical medicine major at Harbin Medical University were recruited and they were randomly allocated into two groups: the control group which was subjected to traditional lecture teaching (n = 69), and the experimental group which was subjected to flipped classroom teaching (n = 62). To assess the effect of flipped teaching, the usual performance and final exam scores were used to evaluate the physiology learning effectiveness of students. The correlation between the usual performance and final exam scores by Pearson method was also conducted in the two teaching groups. After course completion, an anonymous questionnaire survey was conducted among the subjects of flipped classroom group to assess students' opinion regarding the flipped classroom teaching. RESULTS: Our results showed that the usual performance and final exam scores of students in the flipped classroom were both significantly higher than that in the traditional teaching class (P < 0.05). Moreover, our results also showed that the usual performance of students was significantly correlated with the final exam scores in the flipped classroom (r = 0.3945, P < 0.01), but not in the traditional teaching group (r = 0.1522, P = 0.2119). The results of questionnaire survey showed that 77.58% of the students believed flipped classroom teaching improved their knowledge acquisition. 70%~86% of students perceived that flipped classroom enhanced their learning abilities, including self-study ability, collaborative learning and problem-solving skills, and clinical thinking ability. In addition, about 60% of students acknowledged the teaching design and teaching environment, more students' engagement and presentation of group learning in the flipped classroom. CONCLUSION: The flipped classroom teaching significantly improved students' learning effectiveness in physiology course, as indicated by final exam score and usual performance. It also promoted higher-order ability-set acquisition and allowed a rationalized formative evaluation system.

Monkeypox and the perinatal period: what does maternal-fetal medicine need to know?

BACKGROUND: After the global elimination of smallpox, monkeypox has become the most threatening orthopoxvirus to human health. Very few studies have been reported on pregnant women and newborns. In the case of monkeypox infection, the virus can cause serious adverse pregnancy events in women, which can lead to fetal or neonatal death. DATA SOURCES: We made a comprehensive review after an extensive literature search in the PubMed/Medline database and websites concerning smallpox and monkeypox. RESULTS: Two case reports reported a total of nine pregnant women, six of whom had fetal deaths. In the autopsy of a stillbirth, researchers found that the placenta was infected with monkeypox virus, but the mechanism of infection remains unclear. Smallpox vaccine should be administered to acutely exposed pregnant women and newborns. Several novel recombinant vaccinia immunogloblin (rVIG) and human-specific monoclonal antibodies are being developed for the prevention and treatment of monkeypox virus infection. After the fetus was delivered, the newborn should take a bath as soon as possible to remove the amniotic fluid and dirt from the body. The appropriate isolation protocol for the newborn should be selected according to the infection status of the mother. It is not known whether monkeypox virus is present in breast milk, and pasteurized breast milk can be given to newborns when breastfeeding is considered. CONCLUSION: This review presents an overview of monkeypox in the perinatal period and guides the future research direction.

[Short-term persistent symptoms in preschool children with mild/common coronavirus disease 2019 caused by Omicron variant infection after discharge: a follow-up study]. / Omicronå˜å¼‚æ ªæ„ŸæŸ“çš„è½»åž‹/æ™®é€šåž‹æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žå­¦é¾„å‰å„¿ç«¥å‡ºé™¢åŽçŸ­æœŸç›¸å ³æŒç»­ç—‡çŠ¶çš„éšè®¿.

OBJECTIVES: To investigate the persistent symptoms in preschool children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection, and to provide a basis for developing follow-up plans after infection and reducing and preventing related symptoms after infection. METHODS: The children, aged 0-5 years, who had Omicron BA.2 infection and were discharged from the pediatric ward of Shanghai Renji Hospital South Branch from April 13 to May 8, 2022, were enrolled as subjects, and related demographic and clinical data were collected. The children were followed up from the time to SARS-CoV-2 clearance for two consecutive tests with an interval of >24 hours till 4-5 weeks after clearance, and telephone follow-up was performed on the primary caregivers to investigate related persistent symptoms. RESULTS: Among the 103 children who met the inclusion criteria, there were 61 boys and 42 girls, with a median age of 18 months. The primary caregivers who had received two or more doses of COVID-19 vaccine accounted for 64.1% (66/103). Fever (98.1%, 101/103) was the most common symptom in these children, followed by cough/expectoration (63.1%, 65/103), gastrointestinal problems (37.9%, 39/103), loss of appetite (30.1%, 31/103), weakness (27.2%, 28/103), and nasal obstruction/runny nose (16.5%, 17/103). The follow-up at 1 month after discharge reported that 44 children (42.7%) had at least one persistent symptom, including respiratory symptoms in 14 children (13.6%) and gastrointestinal problems in 19 children (18.4%). The children whose primary caregivers received two or more doses of COVID-19 vaccine had a significantly shorter time to SARS-CoV-2 clearance than those whose primary caregivers did not receive or only received one dose of COVID-19 vaccine (P<0.05), while there was no significant difference between the two groups in the proportion of children with at least one persistent symptom (P>0.05). CONCLUSIONS: Nearly half of the preschool children may have related persistent symptoms after SARS-CoV-2 Omicron variant infection, mainly gastrointestinal and respiratory symptoms. Most of the symptoms may be mild, and continuous follow-up is needed to observe their outcomes. Vaccination of COVID-19 vaccine for primary caregivers has a certain protective effect on children.

Management experience of a designated hospital for children with coronavirus disease 2019. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žå„¿ç«¥å®šç‚¹åŒ»é™¢ç®¡ç†ç»éªŒåˆ†äº«.

The global pandemic of coronavirus disease 2019 (COVID-19) has brought great challenges to the traditional medical model. During the outbreak of COVID-19 in Shanghai, China, from March to May, 2022, there was a significant increase in the number of pediatric cases due to high transmissibility, immune escape, and vaccine breakthrough capacity of Omicron variants. The designated hospitals for children with COVID-19 served as a connecting link between children's specialized hospitals and mobile cabin hospitals. From April 7 to June 2, 2022, a total of 871 children with COVID-19 were admitted to Renji Hospital, Shanghai Jiao Tong University School of Medicine (South Branch), a designated hospital for children with COVID-19. Among these patients, 568 (65.2%) were children under 3 years old, 870 (99.9%) were mild or moderate, and 1 was severe. This article reports the experience in the management of pediatric cases in this designated hospital, which included the following aspects: establishing an optimal case-admission process; strengthening multidisciplinary standardized diagnosis and treatment; optimizing the management, warning, and rescue system for severe COVID-19; implementing family-centered nursing care; formulating an individualized traditional Chinese medicine treatment regimen; optimizing the discharge process and strengthening bed turnover; implementing strict whole-process control to reduce the risk of nosocomial infection; constructing a structured medical record system and using information platforms to adapt to the work mode of large-volume cases; conducting scientific research and sharing the experience in diagnosis and treatment.

Development of a Promising 18F-Radiotracer for PET Imaging Legumain Activity In Vivo.

Legumain has been found overexpressed in several cancers, which serves as an important biomarker for cancer diagnosis. In this research, a novel fluorine-18 labeled radioactive tracer [18F]SF-AAN targeting legumain was designed and synthesized for positron emission tomography (PET) imaging. Nonradioactive probe [19F]SF-AAN was obtained through chemical and solid phase peptide synthesis. After a simple one-step 18F labeling, the radiotracer [18F]SF-AAN was obtained with a high radiochemical conversion rate (>85%) and radiochemical purity (99%) as well as high molar activity (12.77 ± 0.50 MBq/nmol). The targeting specificity of [18F]SF-AAN for detecting legumain activity was investigated systematically in vitro and in vivo. In vitro cellular uptake assay showed that the uptake of [18F]SF-AAN in legumain-positive MDA-MB-468 cells was twice as much as that in legumain-negative PC-3 cells at 4 h. In vivo PET imaging revealed that the tumor uptake of [18F]SF-AAN in MDA-MB-468 tumor-bearing mice was about 2.7 times of that in PC-3 tumor-bearing mice at 10 min post injection. The experimental results indicated that [18F]SF-AAN could serve as a promising PET tracer for detecting the legumain expression sensitively and specifically, which would be beneficial for the diagnosis of legumain-related diseases.

fNIRS-Based Dynamic Functional Connectivity Reveals the Innate Musical Sensing Brain Networks in Preterm Infants.

Humans have the ability to appreciate and create music. However, why and how humans have this distinctive ability to perceive music remains unclear. Additionally, the investigation of the innate perceiving skill in humans is compounded by the fact that we have been actively and passively exposed to auditory stimuli or have systematically learnt music after birth. Therefore, to explore the innate musical perceiving ability, infants with preterm birth may be the most suitable population. In this study, the auditory brain networks were explored using dynamic functional connectivity-based reliable component analysis (RCA) in preterm infants during music listening. The brain activation was captured by portable functional near-infrared spectroscopy (fNIRS) to simulate a natural environment for preterm infants. The components with the maximum inter-subject correlation were extracted. The generated spatial filters identified the shared spatial structural features of functional brain connectivity across subjects during listening to the common music, exhibiting a functional synchronization between the right temporal region and the frontal and motor cortex, and synchronization between the bilateral temporal regions. The specific pattern is responsible for the functions involving music comprehension, emotion generation, language processing, memory, and sensory. The fluctuation of the extracted components and the phase variation demonstrates the interactions between the extracted brain networks to encode musical information. These results are critically important for our understanding of the underlying mechanisms of the innate perceiving skills at early ages of human during naturalistic music listening.

Stimuli-Responsive Macrocyclization Scaffold Allows In Situ Self-Assembly of Radioactive Tracers for Positron Emission Tomography Imaging of Enzyme Activity.

Target-enabled bioorthogonal reaction and self-assembly of a small-molecule probe into supramolecules have shown promise for molecular imaging. In this paper, we report a new stimuli-responsive bioorthogonal reaction scaffold (SF) for controlling in situ self-assembly by engineering the condensation reaction between 2-cyanobenzothiazole and cysteine. For probes with the SF scaffold, intramolecular cyclization took place soon after activation, which could efficiently outcompete free cysteine even at a low concentration and result in efficient aggregation in the target. Through integration with different enzyme-responsive substrates and an ammoniomethyl-trifluoroborate moiety (AmBF3), two radioactive positron emission tomography (PET) tracers, [18F]SF-DEVD and [18F]SF-Glu, were designed, which showed high stability under physiological conditions and could produce clear PET signal in tumors to detect enzyme activity (e.g., caspase-3, γ-glutamyltranspeptidase) timely and accurately. Our results demonstrated that the scaffold SF could serve as a general molecular scaffold in the development of smart PET tracers for noninvasive imaging of enzyme activity, which could contribute to tumor detection and treatment efficacy evaluation.

Protective Effect of a Water-Soluble Carotenoid-Rich Extract of Cordyceps militaris against Light-Evoked Functional Vision Deterioration in Mice.

Light-evoked retinal photodamage is considered an important factor contributing to functional vision deterioration and can even lead to light maculopathy or dry age-related macular degeneration. Loss of visual acuity (VA) and visual contrast sensitivity function (VCSF) are the major symptoms of retinal degenerative diseases. Cordyceps militaris is a carotenoid-rich Chinese medicinal fungus with antioxidant, anti-inflammatory, and immunomodulatory functions. C. militaris extract is a natural substance, and its bioactive constituents have been shown to confer health benefits, but their application in retinal tissue and functional vision protection in vivo remain incompletely understood. In the present study, we evaluated the influence of water-soluble, carotenoid-rich C. militaris extracts on the visual performance of light-damaged mouse retinas in vivo, using adult female CD-1® (ICR) albino mice. We showed that oral administration of this C. militaris extract (10 mg/kg, twice daily) protected the neural retina tissue against light-evoked photoreceptor cell death, reduced Müller cell hypertrophic gliosis, and elevated GSH levels and promoted the recovery of VA- and VCSF-thresholds, especially for high spatial frequency-characterized vision. These results suggest that, probably because of its water-soluble carotenoids, C. militaris extract has the potential to prevent or treat light-induced visual dysfunction.

Assessment of the effectiveness of BOPPPS-based hybrid teaching model in physiology education.

BACKGROUND: Online teaching has become increasingly common in higher education of the post-pandemic era. While a traditional face-to-face lecture or offline teaching remains very important and necessary for students to learn the medical knowledge systematically, guided by the BOPPPS teaching model, combination of online and offline learning approaches has become an unavoidable trend for maximizing teaching efficiency. However, in physiological education, the effectiveness of combined online teaching and offline teaching models remains poorly assessed. The present study aims at providing an assessment to the hybrid teaching model. METHODS: The study was performed among undergraduate medical students of Class 2017 ~ 2019 in the Physiology course in Harbin Medical University during 2018-2020. Based on established offline teaching model with BOPPPS components in 2018, we incorporated online teaching contents into it to form a hybrid BOPPPS teaching model (HBOPPPS, in brief), preliminarily in 2019 and completely in 2020. HBOPPPS effectiveness was assessed through comparing the final examination scores of both objective (multi-choice and single answer questions) and subjective (short and long essays) questions between classes taught with different modalities. RESULTS: The final examination score of students in Class 2019 (83.9 ± 0.5) who were taught with the HBOPPPS was significantly higher than that in Class 2017 (81.1 ± 0.6) taught with offline BOPPPS and in Class 2018 (82.0 ± 0.5) taught with immature HBOPPPS. The difference mainly attributed to the increase in average subjective scores (41.6 ± 0.3 in Class 2019, 41.4 ± 0.3 in Class 2018, and 38.2 ± 0.4 in Class 2017). In the questionnaire about the HBOPPPS among students in Class 2019, 86.2% responded positively and 79.4% perceived improvement in their learning ability. In addition, 73.5% of the students appreciated the reproducibility of learning content and 54.2% valued the flexibility of HBOPPPS. Lastly, 61.7% of the students preferred the HBOPPPS relative to BOPPPS in future learning. CONCLUSIONS: HBOPPPS is likely a more effective teaching model and useful for enhancing effectiveness of Physiology teaching. This is attributable to the reproducibility and flexibility as well as the increased learning initiatives.

Vitamin D stimulates placental L-type amino acid transporter 1 (LAT1) in preeclampsia.

Vitamin D insufficiency/deficiency has been linked to an increased risk of preeclampsia. Impaired placental amino acid transport is suggested to contribute to abnormal fetal intrauterine growth in pregnancies complicated by preeclampsia. However, if vitamin D-regulated amino acid transporter is involved in the pathophysiologic mechanism of preeclampsia has not been clarified yet. The aberrant expression of key isoform of L-type amino acid transporter LAT1 was determined by western blot and immunohistochemistry in the placenta from normotensive and preeclamptic pregnancies. The role for vitamin D on placental LAT1 expression was investigated through the exposure of HTR-8/SVneo human trophoblast cells to the biologically active 1,25(OH)2D3 and the oxidative stress-inducer cobalt chloride (CoCl2). Our results showed that placental LAT1 expression was reduced in women with preeclampsia compared to normotensive pregnancies, which was associated with decreased expression of vitamin D receptor (VDR). 1,25(OH)2D3 significantly upregulated LAT1 expression in placental trophoblasts, and also prevented the decrease of mTOR activity under CoCl2-induced oxidative stress. siRNA targeting VDR significantly attenuated 1,25(OH)2D3-stimulated LAT1 expression and mTOR signaling activity. Moreover, treatment of rapamycin specifically inhibited the activity of mTOR signaling and resulted in decrease of LAT1 expression. In conclusion, LAT1 expression was downregulated in the placenta from women with preeclampsia. 1,25(OH)2D3/VDR could stimulate LAT1 expression, which was likely mediated by mTOR signaling in placental trophoblasts. Regulation on placental amino acid transport may be one of the mechanisms by which vitamin D affects fetal growth in preeclampsia.