Three-Axis Vector Magnetometer with a Three-Dimensional Flux Concentrator.

This research proposes a magnetic field sensor with spatial orientation ability. Through the assistance of a magnetic flux concentrator, out-of-plane magnetic flux can be concentrated and guided into the planar magnetic cores of a fluxgate sensor. A printed circuit board is used to construct the basic planar structure, on which the proposed three-dimensional magnetic flux concentrator and magnetic cores are assembled. This reduces the alignment error of the coils and improves the reliability of the sensor. Three-axis sensing is achieved by using the second harmonic signals from selected sensing coil pairs. The magnetometer exhibits a linear range to 130 µT. At an excitation frequency of 50 kHz, the measured sensitivities are 257.1, 468.8, and 258.8 V/T for the X-, Y-, and Z-axis sensing modes, respectively. This sensor utilizes only one sensing mechanism for the vector field, making it suitable for IoT applications, especially for assessing mechanical posture or position.

Cre-LoxP and tamoxifen-induced deletion of ovarian quiescin sulfhydryl oxidase 2 showed disruption of ovulatory activity in mice.

BACKGROUND: Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function. RESULTS: We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions. CONCLUSION: Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.

Assessment of Heart Rate Monitoring During Exercise With Smart Wristbands and a Heart Rhythm Patch: Validation and Comparison Study.

BACKGROUND: The integration of wearable devices into fitness routines, particularly in military settings, necessitates a rigorous assessment of their accuracy. This study evaluates the precision of heart rate measurements by locally manufactured wristbands, increasingly used in military academies, to inform future device selection for military training activities. OBJECTIVE: This research aims to assess the reliability of heart rate monitoring in chest straps versus wearable wristbands. METHODS: Data on heart rate and acceleration were collected using the Q-Band Q-69 smart wristband (Mobile Action Technology Inc) and compared against the Zephyr Bioharness standard measuring device. The Lin concordance correlation coefficient, Pearson product moment correlation coefficient, and intraclass correlation coefficient were used for reliability analysis. RESULTS: Participants from a Northern Taiwanese medical school were enrolled (January 1-June 31, 2021). The Q-Band Q-69 demonstrated that the mean absolute percentage error (MAPE) of women was observed to be 13.35 (SD 13.47). Comparatively, men exhibited a lower MAPE of 8.54 (SD 10.49). The walking state MAPE was 7.79 for women and 10.65 for men. The wristband's accuracy generally remained below 10% MAPE in other activities. Pearson product moment correlation coefficient analysis indicated gender-based performance differences, with overall coefficients of 0.625 for women and 0.808 for men, varying across walking, running, and cooldown phases. CONCLUSIONS: This study highlights significant gender and activity-dependent variations in the accuracy of the MobileAction Q-Band Q-69 smart wristband. Reduced accuracy was notably observed during running. Occasional extreme errors point to the necessity of caution in relying on such devices for exercise monitoring. The findings emphasize the limitations and potential inaccuracies of wearable technology, especially in high-intensity physical activities.

Innovative technology for evaluation of sperm DNA double-strand breaks diagnoses male factor infertility and prevents reproductive failures.

Neutral comet assay has been available for two decades to evaluate sperm double-strand breaks (DSBs). However, its clinical usability is limited due to its complex and time-consuming procedure, as well as the lack of a standardized scoring system. The aim of this study was to: develop a rapid diagnostic method for DSBs, Sperm DNA Fragmentation Releasing Assay (SDFR), and explore the association between DSBs and reproductive outcomes. We pioneered the use of polyacrylamide (PA) for embedding sperm chromatin and optimized the porosity of PA to be between 10 and 13%. The refined PA network allowed the trapping of DSBs, which dispersed halo on an immunological slide; in contrast, intact chromatin failed to develop a halo. A strong correlation was showed between reproducible values obtained from SDFR and neutral comet assay. SDFR were responsive to dose-/time-dependent simulated DSBs, indicating high sensitivity and specificity. Furthermore, we conducted a retrospective study of couples with embryonic aneuploidy screening, and recording DSB profiles of the male partners. Our findings revealed that DSB enabled to predict embryonic aneuploidy whereas basic semen parameters did not. In conclusion, SDFR offers a rapid and user-friendly approach for evaluating DSBs, with potential implications for predictive healthcare in reproductive medicine.

Antioxidant Nanoparticles Restore Cisplatin-Induced Male Fertility Defects by Promoting MDC1-53bp1-Associated Non-Homologous DNA Repair Mechanism and Sperm Intracellular Calcium Influx.

Introduction: Cisplatin, a commonly used anticancer compound, exhibits severe off-target organ toxicity. Due to its wide application in cancer treatment, the reduction of its damage to normal tissue is an imminent clinical need. Cisplatin-induced testicular oxidative stress and damage lead to male sub- or infertility. Despite earlier studies showing that the natural polyphenol extracts honokiol serve as the free radical scavenger that reduces the accumulation of intracellular free radicals, whether honokiol exhibits direct effects on the testis and sperm is unclear. Thus, the aim of the current study is to investigate the direct effects of honokiol on testicular recovery and sperm physiology. Methods: We encapsulated this polyphenol antioxidation compound into liposome-based nanoparticles (nHNK) and gave intraperitoneally to mice at a dosage of 5 mg/kg body mass every other day for consecutive 6 weeks. Results: We showed that nHNK promotes MDC1-53bp1-associated non-homologous DNA double-strand break repair signaling pathway that minimizes cisplatin-induced DNA damage. This positive effect restores spermatogenesis and allows the restructuring of the multi-spermatogenic layers in the testis. By reducing mitochondrial oxidative damage, nHNK also protects sperm mitochondrial structure and maintains both testicular and sperm ATP production. By a yet-to-identify mechanism, nHNK restores sperm calcium influx at the sperm midpiece and tail, which is essential for sperm hypermotility and their interaction with the oocyte. Discussion: Taken together, the nanoparticulated antioxidant counteracts cisplatin-induced male fertility defects and benefits patients undertaking cisplatin-based chemotherapy. These data may allow the reintroduction of cisplatin for systemic applications in patients at clinics with reduced testicular toxicity.

L1cam alternative shorter transcripts encoding the extracellular domains were overexpressed in the intestine of L1cam knockdown mice.

Hirschsprung disease (HSCR) is a congenital disorder of functional bowel obstruction due to the absence of enteric ganglia in distal bowel. Different L1cam variants were reportedly associated with L1cam syndrome and HSCR, whose phenotypes lacked predictable relevance to their genotypes. Using next-generation sequencing (NGS), we found an L1CAM de novo frameshift mutation in a female with mild hydrocephalus and skip-type HSCR. A nearly identical L1cam variant was introduced into FVB/NJ mice via the CRISPR-EZ method. A silent mutation was created via ssODN to gain an artificial Ncol restriction enzyme site for easier genotyping. Six L1cam protein-coding alternative transcripts were quantitatively measured. Immunofluorescence staining with polyclonal and monoclonal L1cam antibodies was used to characterize L1cam isoform proteins in enteric ganglia. Fifteen mice, seven males and eight females, generated via CRISPR-EZ, were confirmed to carry the L1cam frameshift variant, resulting in a premature stop codon. There was no prominent hydrocephalus nor HSCR-like presentation in these mice, but male infertility was noticed after observation for three generations in a total of 176 mice. Full-length L1cam transcripts were detected at a very low level in the intestinal tissues and almost none in the brain of these mice. Alternative shorter transcripts encoding the extracellular domains were overexpressed in the intestine of L1cam knockdown mice. Immunofluorescence confirmed no fulllength L1cam protein in enteric ganglia. These shorter L1cam isoform proteins might play a role in protecting L1cam knockdown mice from HSCR.

Live motile sperm sorting device for enhanced sperm-fertilization competency: comparative analysis with density-gradient centrifugation and microfluidic sperm sorting.

PURPOSE: A live motile sperm sorting device (LensHooke® CA0) developed to prevent the deleterious effects of centrifugation was evaluated comparatively with conventional density-gradient centrifugation (DGC) and microfluidic-based device (Zymot) in sperm selection. METHODS: Semen samples from 239 men were collected. CA0 under different incubation intervals (5, 10, 30, and 60 min) and temperatures (20, 25, and 37℃) was conducted. The sperm quality in CA0-, DGC-, and Zymot-processed samples was then comparatively evaluated. Semen parameters included concentration, motility, morphology, motion kinematics, DNA fragmentation index (DFI), and the rate of acrosome-reacted sperm (AR). RESULTS: Total motility and motile sperm concentration increased in a time- and temperature-dependent manner and the total motility peaked for 30 min at 37℃. In paired analysis, CA0 showed significantly higher total motility (94.0%), progressive motility (90.8%), rapid progressive motility (83.6%), normal morphology (10.3%), and lower DFI (2.4%) and AR (4.7%) than the other two methods in normozoospermic samples (all p < 0.05). For non-normozoospermic samples, CA0 had significantly better results than the other two methods (total motility 89.2%, progressive motility 80.4%, rapid progressive motility 74.2%, normal morphology 8.5%, DFI 4.0%, and AR 4.0%; all p < 0.05). CONCLUSION: CA0 yielded spermatozoa with enhanced sperm fertilization potentials; DFI was minimized in samples processed by CA0. CA0 was effective for both normal and abnormal semen samples due to its consistent selection efficiency.

Development and integration of LensHooke® R10 for automatic and standardized diagnosis for sperm DNA fragmentation.

BACKGROUND: The sperm chromatin dispersion assay is commonly used to assess sperm DNA integrity. This approach is time-consuming, demonstrates poor chromatin preservation, and provides an ambiguous and unstandardized evaluation of fragmented chromatin. OBJECTIVES: We aimed to (i) develop an optimized sperm chromatin dispersion assay with reduced operation time, (ii) validate R10 test accuracy by comparing it to a conventional sperm chromatin dispersion assay, and (iii) standardize the sperm DNA fragmentation analysis procedure by integrating artificial intelligence optical microscopic technology. MATERIALS AND METHODS: This cross-section study included 620 semen samples. Aliquots were analyzed by a conventional Halosperm® G2 assay (G2) and LensHooke® R10 assay (R10). The DNA fragmentation index was scored manually, and R10 slides were automatically determined by a LensHooke® X12 PRO semen analysis system (X12). RESULTS: We demonstrated significant improvements in total assay time (40 vs. 72 min, p < 0.001) and in the halo-cytological resolution using R10 compared to G2. Comparing the G2 and R10, DNA fragmentation index results demonstrated good agreement between the two methods (Spearman's rank correlation, rho = 0.8517, p < 0.0001). We introduced the integration of an auto-calculation system to diagnose sperm DNA fragmentation. X12 interpretation showed excellent agreement with manual interpretation (Spearman's rank correlation, rho = 0.9323, p < 0.0001), but had a low coefficient of variation compared to manual interpretation (4% for R10 by X12 vs. 19% for R10 by manual scoring vs. 25% for G2 by manual scoring). DNA fragmentation index was more correlated with total motility (coefficients = -0.3607, p < 0.0001) than sperm morphology and was positively associated with asthenozoospermic semen samples (p = 0.0001). CONCLUSION: The R10 sperm chromatin dispersion assay combined with the X12 semen analysis system is faster, more objective, and provides standardization for sperm DNA fragmentation.

Two-in-One Nanoparticle Formulation to Deliver a Tyrosine Kinase Inhibitor and microRNA for Targeting Metabolic Reprogramming and Mitochondrial Dysfunction in Gastric Cancer.

Dysregulational EGFR, KRAS, and mTOR pathways cause metabolic reprogramming, leading to progression of gastric cancer. Afatinib (Afa) is a broad-spectrum tyrosine kinase inhibitor that reduces cancer growth by blocking the EGFR family. MicroRNA 125 (miR-125) reportedly diminishes EGFRs, glycolysis, and anti-apoptosis. Here, a one-shot formulation of miR-125 and Afa was presented for the first time. The formulation comprised solid lipid nanoparticles modified with mitochondrial targeting peptide and EGFR-directed ligand to suppress pan-ErbB-facilitated epithelial-mesenchymal transition and mTOR-mediated metabolism discoordination of glycolysis-glutaminolysis-lipids. Results showed that this cotreatment modulated numerous critical proteins, such as EGFR/HER2/HER3, Kras/ERK/Vimentin, and mTOR/HIF1-α/HK2/LDHA pathways of gastric adenocarcinoma AGS cells. The combinatorial therapy suppressed glutaminolysis, glycolysis, mitochondrial oxidative phosphorylation, and fatty acid synthesis. The cotreatment also notably decreased the levels of lactate, acetyl-CoA, and ATP. The active involvement of mitophagy supported the direction of promoting the apoptosis of AGS cells, which subsequently caused the breakdown of tumor-cell homeostasis and death. In vivo findings in AGS-bearing mice confirmed the superiority of the anti-tumor efficacy and safety of this combination nanomedicine over other formulations. This one-shot formulation disturbed the metabolic reprogramming; alleviated the "Warburg effect" of tumors; interrupted the supply of fatty acid, cholesterol, and triglyceride; and exacerbated the energy depletion in the tumor microenvironment, thereby inhibiting tumor proliferation and aggressiveness. Collectively, the results showed that the two-in-one nanoparticle formulation of miR-125 and Afa was a breakthrough in simplifying drug preparation and administration, as well as effectively inhibiting tumor progression through the versatile targeting of pan-ErbB- and mTOR-mediated mitochondrial dysfunction and dysregulated metabolism.

Cognitive Screening via Comprehensive Geriatric Assessment of Older Patients for the Risk Factors of Hospital Revisit/Readmission after Emergency Department Visit at 3-Month Follow-Up.

INTRODUCTION: Cognitive impairment (COIM) is a major challenge for healthcare systems and is associated with an increased risk of adverse outcomes in older people visiting emergency departments (EDs). Owing to global aging, both cognitive screening and comprehensive geriatric assessment (CGA) application in ED settings are developing areas of geriatric emergency medicine. Meanwhile, the association between clinical outcomes of COIM; cognitive impairment, no dementia (CIND); and dementia in the ED could be better investigated. Our study aims to identify individuals with COIM from older patients in the ED via CGA and to describe the association of CIND and dementia with prognosis in ED visits. METHODS: A prospective cross-sectional study was conducted in the ED of the Taipei Veterans General Hospital, a medical center located in Taipei, Taiwan, from August 2018 to November 2020. Patients aged ≥75 years with and without COIM were compared using data obtained from the CGAs conducted by trained nurses. RESULTS: A total of 823 older patients were enrolled in the study and underwent CGA. Of these, 463 (56.3%) were diagnosed with COIM, of which 292 (35.5%) were diagnosed with dementia; and 171 (20.8%), CIND. Between the no-COIM and COIM groups, the COIM group had a higher rate of hospital admission (p = 0.002) and mortality at 3 months (p < 0.05). Among the no-COIM, CIND, and dementia groups, ED disposition (p = 0.001) and the rate of revisit/readmission (p < 0.05) showed significant differences. In particular, the dementia group had a significantly higher rate of revisit/readmission as compared to the CIND group among the three groups. DISCUSSION/CONCLUSION: Older patients with COIM had a higher rate of hospital admission and mortality at the 3-month follow-up than older patients without COIM. Among the no-COIM, CIND, and dementia groups, patients with dementia had significantly increased risks of hospital admission and revisit/readmission. The early detection of COIM, and even dementia, could help ED physicians formulate strategies with geriatric specialists to improve mortality outcomes and revisit/readmission.

3D structure and in situ arrangements of CatSper channel in the sperm flagellum.

The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway. Here, we applied cryo-electron tomography to visualize the higher-order organization of the native CatSper complex in intact mammalian sperm. The repeating CatSper units form long zigzag-rows along mouse and human sperm flagella. Above each tetrameric channel pore, most of the extracellular domains form a canopy that interconnects to a zigzag-shaped roof. Murine CatSper contains an additional wing-structure connected to the tetrameric channel. The intracellular domains link two neighboring channels to a diagonal array, suggesting a dimer formation. Fitting of an atomic model of isolated monomeric CatSper to the in situ map reveals supramolecular interactions and assembly of the CatSper complex. Loss of EFCAB9-CATSPERζ alters the architecture and interactions of the channels, resulting in fragmentation and misalignment of the zigzag-rows and disruption of flagellar movement in Efcab9-/- sperm. This work offers unique insights into the structural basis for understanding CatSper regulation of sperm motility.

A 44-Year-Old Man With Acute Mutism: Acute Stroke, Psychiatric Disorder, or Substance Abuse?

Mutism is a common presentation of psychiatric diseases. However, patients presenting to the emergency department with mutism should be assumed to have an organic pathology irrespective of their psychiatric history. Little is known about the causality between mutism and illicit drug use. We report a case of a 44-year-old man with acute mutism who was initially diagnosed with ischemic cerebral infarction involving the dorsolateral frontal cortex causing Broca's aphasia. He was later found to have a history of amphetamine, ketamine, and new psychoactive substance use. Substance abuse could be a precipitating factor for acute stroke, especially among patients aged below 55 years. Patients should be routinely screened and counseled regarding illicit drug use. The present case report highlights the possibility that transient ischemia could be associated with acute mutism in drug abusers. Prompt acquisition of drug abuse history or basic drug screening is especially mandatory.

Comparison of outcomes in emergency department revisiting patients before and after coronavirus disease 2019 epidemic.

BACKGROUND AND IMPORTANCE: The outbreak of COVID-19 challenged the global health system and specifically impacted the emergency departments (EDs). Studying the quality indicators of ED care under COVID-19 has been a necessary task, and ED revisits have been used as an indicator to monitor ED performance. OBJECTIVES: The study investigated whether discrepancies existed among ED revisiting cases before and after COVID-19 and whether the COVID-19 epidemic was a predictor of poor outcomes of ED revisits. DESIGN: Retrospective study. SETTINGS AND PARTICIPANTS: We used electronic health records data from a tertiary medical center. Data of patients with 72-h ED revisit after the COVID-19 epidemic were collected from February 2020 to June 2020 and compared with those of patients before COVID-19, from February 2019 to June 2019. OUTCOME MEASURES AND ANALYSIS: The investigated outcomes included hospital admission, ICU admission, out-of-hospital cardiac arrest, and subsequent inhospital mortality. Univariate and multivariate logistic regression models were used to identify independent predictors of 72-h ED revisit outcomes. MAIN RESULTS: In total, 1786 patients were enrolled in our study - 765 in the COVID group and 1021 in the non-COVID group. Compared with the non-COVID group, patients in the COVID group were younger (53.9 vs. 56.1 years old; P = 0.002) and more often female (66.1% vs. 47.3%; P < 0.001) and had less escalation of triage level (11.6% vs. 15.0%; P = 0.041). The hospital admission and inhospital mortality rates in the COVID and non-COVID groups were 33.9% vs. 32.0% and 2.7% vs. 1.5%, respectively. In the logistic regression model, the COVID-19 period was significantly associated with inhospital mortality (adjusted odds ratio, 2.289; 95% confidence interval, 1.059-4.948; P = 0.035). CONCLUSION: Patients with 72-h ED revisits showed distinct demographic and clinical patterns before and after the COVID-19 epidemic; the COVID-19 period was an independent predictor of increased inhospital mortality.

Gastric Mobility and Gastrointestinal Hormones in Older Patients with Sarcopenia.

Sarcopenia has serious clinical consequences and poses a major threat to older people. Gastrointestinal environmental factors are believed to be the main cause. The aim of this study was to describe the relationship between sarcopenia and gastric mobility and to investigate the relationship between sarcopenia and the concentration of gastrointestinal hormones in older patients. Patients aged ≥ 75 years were recruited for this prospective study from August 2018 to February 2019 at the emergency department. The enrolled patients were tested for sarcopenia. Gastric emptying scintigraphy was conducted, and laboratory tests for cholecystokinin(CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), nesfatin, and ghrelin were performed during the fasting period. We enrolled 52 patients with mean age of 86.9 years, including 17 (32.7%) patients in the non-sarcopenia group, 17 (32.7%) patients in the pre-sarcopenia group, and 18 (34.6%) in the sarcopenia group. The mean gastric emptying half-time had no significant difference among three groups. The sarcopenia group had significantly higher fasting plasma concentrations of CCK, GLP-1, and PYY. We concluded that the older people with sarcopenia had significantly higher plasma concentrations of CCK, GLP-1, and PYY. In the elderly population, anorexigenic gastrointestinal hormones might have more important relationships with sarcopenia than orexigenic gastrointestinal hormones.

Polarized epithelium-sperm co-culture system reveals stimulatory factors for the secretion of mouse epididymal quiescin sulfhydryl oxidase 1.

Spermatozoa acquire fertilization ability through post-translational modifications. These membrane surface alterations occur in various segments of the epididymis. Quiescin sulfhydryl oxidases, which catalyze thiol-oxidation reactions, are involved in disulfide bond formation, which is essential for sperm maturation, upon transition and migration in the epididymis. Using castration and azoospermia transgenic mouse models, in the present study, we showed that quiescin sulfhydryl oxidase 1 (QSOX1) protein expression and secretion are positively correlated with the presence of testosterone and sperm cells. A two-dimensional in vitro epithelium-sperm co-culture system provided further evidence in support of the notion that both testosterone and its dominant metabolite, 5α-dihydrotestosterone, promote epididymal QSOX1 secretion. We also demonstrated that immature caput spermatozoa, but not mature cauda sperm cells, exhibited great potential to stimulate QSOX1 secretion in vitro, suggesting that sperm maturation is a key regulatory factor for mouse epididymal QSOX1 secretion. Proteomic analysis identified 582 secretory proteins from the co-culture supernatant, of which 258 were sperm-specific and 154 were of epididymal epithelium-origin. Gene Ontology analysis indicated that these secreted proteins exhibit functions known to facilitate sperm membrane organization, cellular activity, and sperm-egg recognition. Taken together, our data demonstrated that testosterone and sperm maturation status are key regulators of mouse epididymal QSOX1 protein expression and secretion.

Geriatric syndromes predict mortality of people aged 75+ years in the observation room of emergency department: Towards function-centric emergency medicine.

BACKGROUND: Aging is a complex process involving functional decline, reduced physiological reserve, increased multimorbidity, and impaired homeostasis, all of which collectively generate various health risks for older adults. To predict short-term mortality of non-critical older patients in the observation room of the emergency department (ED) based on function-centric approach instead of disease-centric one. METHODS: We conducted a prospective study enrolling 831 patients aged 75 years and older between 2018 and 2020. Comprehensive geriatric assessment was performed on all patients, and the results were integrated into the care planning process. RESULTS: In total 831 patients (mean age: 84.8 ± 5.8 years) were enrolled and the post-discharge mortality rate was 3.3% (28 deaths) after 3 months, and 5.4% (45 deaths) after 6 months. The independent predictors of 3-month mortality were malnutrition (adjusted odds ratio [OR], 4.77; p < 0.05), incontinence (adjusted OR, 2.58; p < 0.05) and multimorbidity (adjusted OR, 1.51; p < 0.001). For 6-month mortality, malnutrition (adjusted OR, 4.20; p < 0.01), multimorbidity (adjusted OR, 1.40; p < 0.001) and activities of daily living (adjusted OR, 0.99; p < 0.05) were all independent predictors. CONCLUSION: Although ED aims to treat acute and life-threatening conditions, older persons with geriatric syndromes are also at a substantially high risk of adverse outcomes, even mortality. Transitioning of the ED from disease-centric to function-centric services is important for responding to the changing health care needs of super-aged societies.

Echinacoside exhibits antidepressant-like effects through AMPAR-Akt/ERK-mTOR pathway stimulation and BDNF expression in mice.

BACKGROUND: Several natural products have been demonstrated to be effective in the treatment of depressive disorders. Echinacoside, a naturally occurring phenol extracted from Cistanche tubulosa, Echinacea angustifolia, and Cistanche spp, has a wide range of physiological effects, such as antioxidation, neuroprotection, anti-inflammatory, and immunoregulation, which are closely related to depression. In addition, echinacoside can activate protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) in the brain. A key downstream event of the Akt, ERK, and BDNF signaling pathways, namely mechanistic target of rapamycin (mTOR) signaling, plays a crucial role in generating an rapid antidepressant effect. Thus, echinacoside is a promising therapeutic agent for depression. However, research regarding the role of echinacoside in antidepressant effect and brain mTOR activation remains lacking. MATERIALS AND METHODS: The forced swimming test and Western blot analysis in C57BL/6 mice was used to investigate the antidepressant-like activities of echinacoside and the underlying mechanism involved inα-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-Akt/ERK-mTOR pathway. RESULTS: We confirmed the suggestions by previous reports that echinacoside activates Akt/ERK signaling and further demonstrated that echinacoside could provide antidepressant-like effects in mice via the activation of AMPAR-Akt/ERK-mTOR pathway in the hippocampus. CONCLUSIONS: To the best of our knowledge, our study is the first to reveal that echinacoside is a potential treatment for depressive disorders. Moreover, the present study suggests a mechanism for the neuroprotective effect of echinacoside.

Enhancing the learning and transfer of preprocedural communication skills during clerkship using audio-visual material: a prospective case-controlled study over 2 years.

OBJECTIVE/DESIGN/SETTING: This study aims to develop preprocedural communication-specific framework that emphasises the use of audiovisual materials and compares its acceptability by trainees with a regular module. TRAINEES: Between October 2018 and July 2021, 96 medical clerks were enrolled and randomly divided into regular and intervention groups. Another 48 trainees whose did not join the framework-based training but complete self-assessments were enrolled as the control group. INTERVENTIONS: In the intervention training module, the key steps of preprocedural communication-specific skills were structuralised into a framework using the acronym of OSCAR. PRIMARY AND SECONDARY OUTCOME MEASURES: This study compared the acceptability of trainees for two modules by measuring the degree of increase in the end-of-rotation and follow up (4 weeks later) competency from baseline by trainees' self-assessments and physician assessments after serial trainings. RESULTS: In comparison with regular group trainees, greater degree of improvements (framework-1 statement: 111%±13% vs 27%±5%, p<0.001; framework-2 statement: 77%±9% vs 48%±2%, p<0.05; skill-1 statement: 105%±9% vs 48%±3%, p<0.001); skill-2 statement: 71%±11% vs 50%±9%, p<0.05) were noted in the framework-related and skill-related statement 1-2 (the familiarity and confidence to use the framework and skills) than those of intervention group. At the end-of-rotation stage, the trainees ability to use the 'A-step: using audiovisual materials' of the OSCAR was significantly improved (229%±13%, p<0.001), compared with other steps. In the intervention group, the degree of improvement of the end-of-rotation data of trainees' self-assessment from baseline was significantly correlated with the degree of the improvement in physicians' assessment data in the aspects of skills, framework and steps in framework (R=0.872, p<0.01; R=0.813, p<0.001; R=0.914, p<0.001). CONCLUSIONS: The OSCAR framework-based intervention module is well accepted by medical clerks and motivates them to integrate the acquired skills in clinical practice, which leads to trainees' primary care patients being satisfied with their preprocedural communication.

Elucidate multidimensionality of type 1 diabetes mellitus heterogeneity by multifaceted information.

Type 1 diabetes (T1D) is an autoimmune disease. Different factors, including genetics and viruses may contribute to T1D, but the causes of T1D are not fully known, and there is currently no cure. The advent of high-throughput technologies has revolutionized the field of medicine and biology, and analysis of multi-source data along with clinical information has brought a better understanding of the mechanisms behind disease pathogenesis. The aim of this work was the development of a data repository linking clinical information and interactome studies in T1D. To address this goal, we analyzed the electronic health records and online databases of genes, proteins, miRNAs, and pathways to have a global view of T1D. There were common comorbid diseases such as anemia, hypertension, vitreous diseases, renal diseases, and atherosclerosis in the phenotypic disease networks. In the protein-protein interaction network, CASP3 and TNF were date-hub proteins involved in several pathways. Moreover, CTNNB1, IGF1R, and STAT3 were hub proteins, whereas miR-155-5p, miR-34a-5p, miR-23-3p, and miR-20a-5p were hub miRNAs in the gene-miRNA interaction network. Multiple levels of information including genetic, protein, miRNA and clinical data resulted in multiple results, which suggests the complementarity of multiple sources. With the integration of multifaceted information, it will shed light on the mechanisms underlying T1D; the provided data and repository has utility in understanding phenotypic disease networks for the potential development of comorbidities in T1D patients as well as the clues for further research on T1D comorbidities.

Secretory mouse quiescin sulfhydryl oxidase 1 aggregates defected human and mouse spermatozoa in vitro and in vivo.

A flavin-dependent enzyme quiescin Q6 sulfhydryl oxidase 1 (QSOX1) catalyzes the oxidation of thiol groups into disulfide bonds. QSOX1 is prominently expressed in the seminal plasma. However, its role in male reproduction is elusive. Here, we purified the secreted form of QSOX1, i.e., QSOX1c, from mouse seminal vesicle secretions and revealed for the first time its function involved in sperm physiology. Exogenous addition of QSOX1c time-dependently promoted the in vitro aggregation of thiol-rich, oxidative stressed, and apoptotic mouse and human sperm cells. Also, in vivo aggregated sperm cells collected from mouse uterine and human ejaculates also showed high levels of QSOX1c, intracellular reactive oxygen species, annexin V, and free thiols. In summary, our studies demonstrated that QSOX1c could agglutinate spermatozoa susceptible to free radical attack and apoptosis. This characteristic may provide an opportunity to separate defective sperm cells and improve sperm quality before artificial insemination in humans and animals.