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A 27-year-old man was admitted to the hospital after a year of marriage due to infertility. During laparoscopic exploratory surgery, the presence of a retrovesical uterus was clearly observed, and the gonadal organs were visible on both sides. However, the testicles or ovaries were not identifiable, nor were the spermatic vessels and fallopian tubes at the joint. Intraoperative bilateral gonad biopsy was performed. Cryopreservation of the right gonadal gland revealed gonadoblastoma and malignant germinoma (asexual tumor/seminoma) with sclerosis and atrophy of testicular tissue. No proliferation of germ cells and sertoli cells was observed in spermatic tubule. The left gonad was diagnosed as a gonadoblastoma. Finally, total hysterectomy and bilateral gonadal tumor organectomy were performed to seal the vaginal stump. Local radiotherapy was administered after surgery. In general, tumors were found on both sides of the gonads, especially gonadoblastoma and malignant germinoma on the right side and gonadoblastoma on the left side. [ABSTRACT FROM AUTHOR]

Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future. [ABSTRACT FROM AUTHOR]

Inbreeding is thought to be a key adverse factor impacting the genetic quality of seeds in seed production populations and the inbreeding degree (i.e., selfing or outcrossing rate) of seed production populations have been extensively assessed through mating system analysis. The adverse effect of inbreeding on seed quality traits in seed production populations under open-pollination conditions has not yet been clearly described. In this study, the open-pollinated seeds were collected from 26 mother trees in a 58-year-old seed tree stand. Three seed quality traits, including thousand-seed weight (TSW), germination rate (GR), and germination potential (GP), were measured, and the seeds from eight of 26 families with significant differences in seed quality traits were genotyped through twelve microsatellite markers. In addition, the seeds and sprouts (germinated seeds) from six families were genotyped to reveal the effect of inbreeding on seed germination. The three seed quality traits significantly differed among families (p < 0.001). The multilocus outcrossing rate (tm = 0.889) and single-locus outcrossing rate (ts = 0.648) of overall seeds indicated apparent selfing (11.1%) and biparental inbreeding (24.0%). The outcrossing rate in the sprout group (tm = 0.919, ts = 0.788) was higher than that in the seed group (tm = 0.833, ts = 0.646), and the difference in ts between groups was different from zero under the 95% confidence interval (0.024–0.260), suggesting that inbreeding negatively affected seed germination. Linear regression demonstrated that TSW was positively correlated with tm and ts, while GR was negatively related to tm−ts and positively related to ts, implying that seed mass (development) was probably more affected by self-fertilization, but germination capacity was more influenced by biparental inbreeding. The inbreeding depression (ID) of TSW was estimated to be 26.3% with a 0.1 decrease in tm, while that of GR was estimated to be 8.4% with a 0.1 decrease in ts. These results suggest that the IDs during seed development and the germination stage of Masson pine were nonignorable and that more attention to outcrossing rate should be paid to the establishment and management of Masson pine seed production. [ABSTRACT FROM AUTHOR]

In machine learning (ML) problems, it is widely believed that more training samples lead to improved predictive accuracy but incur higher computational costs. Consequently, achieving better data efficiency, that is, the trade-off between the size of the training set and the accuracy of the output model, becomes a key problem in ML applications. In this research, we systematically investigate the data efficiency of Univariate Time Series Anomaly Detection (UTS-AD) models. We first experimentally examine the performance of nine popular UTS-AD algorithms as a function of the training sample size on several benchmark datasets. Our findings confirm that most algorithms become more accurate when more training samples are used, whereas the marginal gain for adding more samples gradually decreases. Based on the above observations, we propose a novel framework called FastUTS-AD that achieves improved data efficiency and reduced computational overhead compared to existing UTS-AD models with little loss of accuracy. Specifically, FastUTS-AD is compatible with different UTS-AD models, utilizing a sampling- and scaling law-based heuristic method to automatically determine the number of training samples a UTS-AD model needs to achieve predictive performance close to that when all samples in the training set are used. Comprehensive experimental results show that, for the nine popular UTS-AD algorithms tested, FastUTS-AD reduces the number of training samples and the training time by 91.09–91.49% and 93.49–93.82% on average without significant decreases in accuracy. [ABSTRACT FROM AUTHOR]

Laboratory courses can help students learn in a meaningful way. In the past, students encountered difficulties in chemistry laboratory courses due to limited access to equipment and space for practicing experimental operations. In recent years, virtual laboratories have allowed students to repeatedly practice in order to achieve their experimental goals. However, even when students follow the experimental protocol, some still cannot fully understand the principles and meaning of the experimental procedures. Therefore, when they encounter unexpected situations in experiments, they may not know how to handle them. Thus, this study incorporated a concept mapping-guided learning approach to facilitate students' understanding of the concepts of the experimental process and the relationship between experimental procedures before virtual laboratory practice. Using a quasi-experimental approach, 51 middle school students aged 12 to 13 years were assigned to an experimental group (M = 12, F = 14) using the concept mapping-guided virtual laboratory learning approach, and a control group (M = 12, F = 13) using the conventional virtual laboratory learning approach. The experimental group improved their science process skills, problem-solving awareness, and creative thinking tendency. Teachers can employ guided virtual laboratory learning approaches to help students experiment and understand concepts. [ABSTRACT FROM AUTHOR]

As a real-time fluid biopsy method, the detection of circulating tumor cells (CTCs) provides important information for the early diagnosis, precise treatment, and prognosis of cancer. However, the low density of CTCs in the peripheral blood hampers their capture and detection with high sensitivity and selectivity using currently available methods. Hence, we designed a sandwich-type electrochemical aptasensor that utilizes holothurian-shaped AuPd nanoparticles (AuPd HSs), tetrahedral DNA nanostructures (TDNs), and CuPdPt nanowire networks (NWs) interwoven with a graphdiyne (GDY) sheet for ultrasensitive non-destructive detection of MCF-7 breast cancer cells. CuPdPt NW–GDY effectively enhanced the electron transfer rate and coupled with the loaded TDNs. The TDNs could capture MCF-7 cells with precision and firmness, and the resulting composite complex was combined with AuPd HSs to form a sandwich-type structure. This novel aptasensor showed a linear range between 10 and 106 cells mL−1 and an ultralow detection limit of 7 cells mL−1. The specificity, stability, and repeatability of the measurements were successfully verified. Moreover, we used benzonase nuclease to achieve non-destructive recovery of cells for further clinical studies. According to the results, our aptasensor was more sensitive measuring the number of CTCs than other approaches because of the employment of TDNs, CuPdPt NW–GDY, and AuPd HSs. We designed a reliable sensor system for the detection of CTCs in the peripheral blood, which could serve as a new approach for cancer diagnosis at an early stage. [ABSTRACT FROM AUTHOR]

Hyperparameter optimization (HPO) methods alleviate the significant effort required to obtain hyperparameters that perform optimally on visual learning problems. Existing methods are computationally inefficient because they are task agnostic (i.e., they do not adapt to a given task). We present HyperSTAR (System for Task Aware Hyperparameter Recommendation), a task-aware HPO algorithm that improves HPO efficiency for a target dataset by using prior knowledge from previous hyperparameter searches to recommend effective hyperparameters conditioned on the target dataset. HyperSTAR ranks and recommends hyperparameters by predicting their performance on the target dataset. To do so, it learns a joint dataset-hyperparameter space in an end-to-end manner that enables its performance predictor to use previously found effective hyperparameters for other similar tasks. The hyperparameter recommendations of HyperSTAR combined with existing HPO techniques lead to a task-aware HPO system that reduces the time to find the optimal hyperparameters for the target learning problem. Our experiments on image classification, object detection, and model pruning validate that HyperSTAR reduces the evaluation of different hyperparameter configurations by about 50 % compared to existing methods and, when combined with Hyperband, uses only 25 % of the budget required by the vanilla Hyperband and Bayesian Optimized Hyperband to achieve the best performance. [ABSTRACT FROM AUTHOR]

Background: This study aims to identify symptom clusters in patients with intermediate and advanced liver cancer receiving targeted immunotherapy, focusing on core and bridge symptoms to establish a foundation for precise symptom management. Methods: This study used a cross-sectional survey and utilized convenience sampling from May 2023 to January 2024 at a third-class hospital in Shanghai, China. The severity of symptoms in liver cancer patients during treatment was evaluated using the Memorial Symptom Assessment Scale. Network analysis was employed to depict the interrelation of symptom clusters and identify core and bridge symptoms. Results: The symptoms were classified by severity into five clusters: oral, gastrointestinal, fatigue-related, body image, and pain-sleep. Within the symptom network, the core symptoms were pain, “I don’t look like myself,” and nausea, while the critical bridge symptoms included pain, itching, and feeling bloated. The strongest connections were observed between nausea and vomiting, followed by taste changes and dry mouth, as well as weight loss and “I don’t look like myself.” Conclusion: In patients receiving targeted immunotherapy for intermediate and advanced liver cancer, multiple symptoms can emerge simultaneously, forming interconnected clusters. By identifying and intervening in core and bridge symptoms, personalized management strategies can be developed to relieve other symptoms and disrupt connections between symptom clusters, thereby enhancing symptom management efficacy. This study has significant clinical and research implications, offering new insights to improve patients’ quality of life and treatment outcomes. [ABSTRACT FROM AUTHOR]

Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk. [ABSTRACT FROM AUTHOR]

Advancements in clinical treatment are increasingly constrained by the limitations of supervised learning techniques, which depend heavily on large volumes of annotated data. The annotation process is not only costly but also demands substantial time from clinical specialists. Addressing this issue, we introduce the S4MI (Self-Supervision and Semi-Supervision for Medical Imaging) pipeline, a novel approach that leverages advancements in self-supervised and semi-supervised learning. These techniques engage in auxiliary tasks that do not require labeling, thus simplifying the scaling of machine supervision compared to fully-supervised methods. Our study benchmarks these techniques on three distinct medical imaging datasets to evaluate their effectiveness in classification and segmentation tasks. Notably, we observed that self-supervised learning significantly surpassed the performance of supervised methods in the classification of all evaluated datasets. Remarkably, the semi-supervised approach demonstrated superior outcomes in segmentation, outperforming fully-supervised methods while using 50% fewer labels across all datasets. In line with our commitment to contributing to the scientific community, we have made the S4MI code openly accessible, allowing for broader application and further development of these methods. The code can be accessed at https://github.com/pranavsinghps1/S4MI. [ABSTRACT FROM AUTHOR]

Context: Elucidating how demography and contemporary landscape features regulate functional connectivity is crucial to implementing effective conservation strategies. We assessed the impacts of landscape features on the genetic variation of a locally endangered carnivore, the leopard cat (Prionailurus bengalensis) in Taiwan. Objectives: We aim to evaluate the association between genetic structure and landscape features. We further predicted the changes in genetic diversity and suitable habitats in the future. Methods: We genotyped 184 leopard cats in western Taiwan using 12 nuclear microsatellites and a mitochondrial marker. We applied a landscape optimization procedure with two genetic distances to identify major genetic barriers and employed ecological niche modeling to predict the future distribution of the leopard cat. Results: Bayesian demographic inferences revealed a dramatic population decline for all leopard cat populations in Taiwan. Genetic clustering and resistance surface modeling supported that the population connectivity was influenced by highways and high elevation. Niche modeling indicated low temperature was one of the primary factors limiting the occurrence of leopard cats that may inhibit their movement in high elevations. We predicted the suitable habitats of leopard cats would shrink northward and towards higher altitudes with rugged topography in response to global warming. Conclusions: Our study provided genetic evidence that leopard cats in Taiwan had undergone a dramatic population decline that may be associated with anthropogenic impacts. We also inferred the anthropogenic linear feature compromised the connectivity and persistence of leopard cats in human-mediated landscapes. Our finding serves as a model for landscape genetic studies of island carnivores in subtropical regions. [ABSTRACT FROM AUTHOR]

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF (+) and NF (−) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF(+) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF(−) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization. [ABSTRACT FROM AUTHOR]

Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients. Cardiac macrophage contributes to the onset of cardiac fibrosis, but the underneath mechanisms remain unclear. Here the authors show that mouse cardiac macrophages from circulating monocytes may trans-differentiate into myofibroblast under hypertensive conditions for fibrosis development, with an AKLBH5/IL11 molecular axis modulating this macrophage-to-myofibroblast transition. [ABSTRACT FROM AUTHOR]

The outbreak of COVID-19 has had a significant impact on the mental health of students. While past research has indicated that leisure activities contribute to well-being, it is not known how leisure activities affect the pathway to sustainable well-being. Therefore, this study constructed a model of sustainable well-being based on emotion-action-experience-outcome with the PERMA model. Chinese vocational colleges and universities were invited using snowball sampling approach to complete the questionnaire. A total of 992 valid questionnaires were collected and validated with structural equation models. The results showed that: (i) Positive emotion had a positive effect on engagement and a positive effect on achievement; (ii) Engagement had a positive effect on interpersonal relationships and meaning; (iii) Achievement had a positive effect on interpersonal relationships and a positive effect on meaning; (iv) Interpersonal relationships had a positive effect on sustainable well-being; and (v) Meaning had a positive effect on sustainable well-being. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, and molnupiravir in adult patients with mild-to-moderate COVID-19. This retrospective cohort study included patients with mild-to-moderate COVID-19 (asymptomatic, mild, and common types) at the First Hospital of Changsha (Hunan Province, China) between March and November 2022. Eligible patients were classified into the azvudine, nirmatrelvir/ritonavir, or molnupiravir groups according to the antiviral agents they received. The outcomes were the times to nucleic acid negative conversion (NANC). This study included 157 patients treated with azvudine (n = 66), molnupiravir (n = 66), or nirmatrelvir/ritonavir (n = 25). There were no statistically significant differences in the time from diagnosis to NANC among the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups [median, 9 (95% CI 9–11) vs. 11 (95% CI 10–12) vs. 9 (95% CI 8–12) days, P = 0.15], time from administration to NANC [median, 9 (95% CI 8–10) vs. 10 (95% CI 9.48–11) vs. 8.708 (95% CI 7.51–11) days, P = 0.50], or hospital stay [median, 11 (95% CI 11–13) vs. 13 (95% CI 12–14) vs. 12 (95% CI 10–14) days, P = 0.14], even after adjustment for sex, age, COVID-19 type, comorbidities, Ct level, time from diagnosis to antiviral treatment, and number of symptoms. The cumulative NANC rates in the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups were 15.2%/12.3%/16.0% at day 5 (P = 0.858), 34.8%/21.5%/32.0% at day 7 (P = 0.226), 66.7%/52.3%/60.0% at 10 days (P = 0.246), and 86.4%/86.2%/80.0% at day 14 (P = 0.721). No serious adverse events were reported. Azvudine may be comparable to nirmatrelvir/ritonavir and molnupiravir in adult patients with mild-to-moderate COVID-19 regarding time to NANC, hospital stay, and AEs. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of individualized nutritional interventions on head and neck cancer (HNC) patients receiving radiotherapy and provide a basis for improving the quality of life for those patients. Methods: A convenience sampling method was adopted to select HNC patients as the study objects. The Nutritional Risk Screening 2002 scale (NRS2002) was used to screen the nutritional risk in 108 HNC patients receiving radiotherapy, and the patients were randomly divided into control group and observation group. Routine dietary guidance was conducted in the control group, and individualized nutritional intervention was applied in the observation group. Results: Six months after the intervention, the albumin levels (37.40 ± 4.03 g/L), hemoglobin levels (128.70 ± 15.22 g/L), and body mass index scores (BMI) (23.96 ± 3.23 kg/m2) of the observation group were all better than to those of control group (t = 2.370, 2.216, and 3.135, respectively, and P < 0.05 in all). Six months after the intervention, the anxiety and depression scores in observation group (27.6 ± 7.2 points, 27.3 ± 2.2 points) were lower than those in control group (38.6 ± 9.6 points, 37.9 ± 3.3 points). The quality-of-life score in the observation group was higher than that in control group. The nursing satisfaction in the observation group (96.43%) was higher than that in the control group (75.00%). Conclusion: The implementation of individualized nutritional intervention has promoted the improvement of laboratory indicators, weight, and BMI of head and neck cancer patients, reduced the risk of malnutrition of head and neck cancer patients, improved their quality of life, reduced the occurrence of adverse reactions during radiotherapy, and promoted long-term efficacy. [ABSTRACT FROM AUTHOR]

Daqu is of great significance to the brewing process of Baijiu, and there are variations in the light-flavor Baijiu Daqu in different regions. However, few studies have been conducted on light-flavor Daqu from the north and south regions of China. In this study, the physicochemical indices, volatile flavor components, and microbial community structure of two types of Daqu from the north and south regions of China were comparatively analyzed. The study findings reveal that Daqu originating from the southern region of China (HB) exhibits superior moisture content, acidity, starch content, and saccharification power. In contrast, Daqu from the northern region of China (SX) displays higher fermentation, esterification, and liquefaction power. The analysis of the microbial community structure revealed that HB was dominated by Bacillus, Kroppenstedtia, Saccharomycopsis, and Thermoascus, while SX was dominated by Bacillus, Prevotella, and Saccharomycopsis. The analysis detected a total of 47 volatile components in both HB Daqu and SX Daqu. The volatile components of pyrazine were significantly more abundant in HB Daqu than in SX Daqu, while alcohol compounds were more prominent in SX Daqu than in HB Daqu. In addition, the RDA analysis established a correlation between dominant microorganisms and volatile components. Cyanobacteria, Fusobacteriota, Ascomycota, Blastocladiomycota, Basidiomycota, and Mucormyce exhibited positive correlations with a significant proportion of the key volatile compounds. This study establishes a scientific foundation for improving the quality of light-flavor Daqu liquor in different regions of China. [ABSTRACT FROM AUTHOR]

An effective analytical method using NTM-COFs on-line pass-through cleanup method and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to simultaneously quantify 12 illicit drugs (norketamine, ketamine, codeine, cocaine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, amphetamine, benzoylecgonine, 6-acetylmorphine, morphine and methadone) in hair sample was developed and validated. The hair sample was extracted with 0.3% formic acid-acetonitrile (v/v) and passed through the nano-titania-modified covalent organic frameworks (NTM-COFs) pre-column to reduce the matrix effect caused by hair specimen. Under the optimal conditions, satisfactory extraction efficiency was obtained for 12 illicit drugs with recoveries between 84.6% and 108.8%. The proposed method was linear for each analyte with correlation coefficients over 0.9926. The limits of detection and limits of quantification for 12 illicit drugs were in the range of 0.012–0.558 ng/g and 0.036–1.860 ng/g, respectively. Acceptable precision and accuracy were also achieved with relative standard deviations values below 9.92% and relative error values below 15.4%. The analytical method was successfully applied to real hair samples from suspected drug abusers, which was proved to be reliable and robust for drug screening in forensic toxicology. [ABSTRACT FROM AUTHOR]

Further study on a 95% EtOH extract of the red mold rice fermented with the mutant of the fungus Monascus sp. led to the isolation of one new natural pyranoid derivative, namely monascuslactone (1), together with three known compounds. The structure of the new compound was determined as (4S*,6S*)-4-hydroxy-4,6-dimethyltetrahydro-2H-pyran-2-one. The known compounds were identified as monascin (2), ankaflavin (3), and methyl N-methyl anthranylate (4). Their structures were elucidated by 1D and 2D NMR spectroscopy together with HR-ESI-MS analysis, and comparison of the spectroscopic data with those reported for structurally related compounds. [ABSTRACT FROM AUTHOR]

Although novel agents for multiple myeloma (MM) have a better response rate and survival in both newly diagnosed and relapsed/refractory MM patients, concerns regarding the association between MM treatments and thromboembolic events have been raised. The aim of this population-based study was to examine the association between different combinations of MM treatments and the risk of thromboembolic events. We conducted a nested case-control study using the Taiwan Cancer Registry (TCR) and National Health Insurance Research Database (NHIRD). Adult patients newly diagnosed with MM and treated with at least one of the immunomodulatory agents between 2008 and 2016 were identified. Among them, we further identified patients who developed thromboembolic events as cases and selected controls matched by age, sex and duration of MM diagnosis at a ratio of 1:5. The index date was defined as the day one year before the diagnosis date of thromboembolic events in the case group and the corresponding date in the control group. Conditional logistic regression was used to examine the association between different MM treatment regimens and the risk of thromboembolic events. A total of 4,180 newly diagnosed MM patients treated with at least one of the immunomodulatory agents were identified (mean age: 67.2 years; male: 55.7%). In this MM cohort, we further identified 388 cases and 1,940 matched controls (mean age: 71 years; male: 64.2%). The use of a thalidomide/bortezomib/steroid combination (odds ratio (OR) 2.95 [95% confidence interval (CI) 1.47–5.95]), thalidomide monotherapy (OR 3.33; 95% CI, 1.59–6.94), and a thalidomide/steroid combination (OR 4.24; 95% CI, 2.00-8.98) were associated with an increased risk of thromboembolic events. Other risk factors, particularly a history of thromboembolic events, including ischemic heart disease and pulmonary embolism, were significantly associated with increased risk of thromboembolic events. We found that the use of thalidomide alone and in specific combinations was associated with an increased risk of thromboembolic events. [ABSTRACT FROM AUTHOR]

Ketamine produces rapid antidepressant effects at sub-anesthetic dosage through early and sustained activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), however, the exact molecular mechanism still remains unclear. Transmembrane AMPAR regulatory protein-γ8 (TARP-γ8) is identified as one of AMPAR auxiliary subunits, which controls assemblies, surface trafficking and gating of AMPARs. Here, we show that ketamine rescues both depressive-like behaviors and the decreased AMPARs-mediated neurotransmission by recruitment of TARP-γ8 at the postsynaptic sites in the ventral hippocampus of stressed male mice. Furthermore, the rapid antidepressant effects of ketamine are abolished by selective blockade of TARP-γ8-containing AMPAR or uncoupling of TARP-γ8 from PSD-95. Overexpression of TARP-γ8 reverses chronic stress-induced depressive-like behaviors and attenuation of AMPARs-mediated neurotransmission. Conversely, knockdown of TARP-γ8 in excitatory neurons prevents the rapid antidepressant effects of ketamine.Ketamine produces rapid antidepressant effects, but the mechanism involved is not fully understood. Here the authors show that ketamine enhances glutamatergic neurotransmission and produces rapid antidepressant-like effects though recruitment of TARP-γ8 at the postsynaptic sites in the ventral hippocampus of stressed male mice. [ABSTRACT FROM AUTHOR]

Swallowing function can deteriorate with age, leading to a risk of dysphagia. Swallowing evaluation by surface electromyography (sEMG) can be easily and extensively applied for an elderly population. This study evaluated the temporal events observed by sEMG to clarify how aging affects the coordination among the masticatory and suprahyoid muscles. We recruited elderly individuals (over 65 years old) who denied dysphagia. The sEMG activities of anterior temporalis, masseter, and suprahyoid muscles were recorded during 3, 15, and 30 ml water swallowing tests (WST). We calculated the time interval between anterior temporalis and suprahyoid peak activity (T-SH interval) and masseter and suprahyoid peak activity (M-SH interval) and analyzed their correlation with age. The subjects who could and could not swallow 30 ml of water in one gulp were further assigned into the one-gulp and piecemeal groups, respectively, for subgroup analysis. We recruited 101 subjects, among whom 75 (26 males and 49 females) were analyzed after excluding those with suspected dysphagia or low-quality sEMG recordings. Age was significantly correlated with the bilateral T-SH (left: r = 0.249, p = 0.031; right: r = 0.412, p < 0.01) and right M-SH (r = 0.242, p = 0.037) intervals in the 30 ml WST. The correlation between intervals and age were observed in both subgroups. sEMG can be used to investigate the effect of aging on the temporal coordination between masticatory and suprahyoid contraction. Further studies are needed to verify the validity of screening subclinical dysphagia in the elderly. [ABSTRACT FROM AUTHOR]

Depression is among the most frequent psychiatric comorbid conditions in Alzheimer disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge, and the data on the efffcacy of current antidepressants used clinically for depressive symptoms in patients with AD remain inconclusive. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD. Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 24 months of age and age- and sex-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT) were implemented to assess the abilities of learning and memory, and the open field test (OFT) and the tail suspension test (TST) were used to assess depression-like behavior. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identified by orthogonal projections to latent structures discriminant analysis (OPLS-DA). Most neurotransmitters exert their effects by binding to the corresponding receptor, so the expression of relative receptors in the hippocampus of mice was detected using Western blot. Compared to WT mice, 3×Tg-AD mice displayed significant cognitive impairment in the PAT and depression-like behavior in the OFT and TST. They also showed significant decreases in the levels of L-tyrosine, norepinephrine, vanillylmandelic acid, 5-hydroxytryptamine, and acetylcholine, in contrast to significant increases in 5-hydroxyindoleacetic acid, L-histidine, L-glutamine, and L-arginine in the hippocampus. Moreover, the expression of the alpha 1a adrenergic receptor (ADRA1A), serotonin 1 A receptor (5HT1A), and γ-aminobutyric acid A receptor subunit alpha-2 (GABRA2) was significantly downregulated in the hippocampus of 3×Tg-AD mice, while histamine H3 receptor (H3R) expression was significantly upregulated. In addition, the ratio of phosphorylated cAMP-response element-binding protein (pCREB) and CREB was significantly decreased in the hippocampus of 3×Tg-AD mice than WT mice. We demonstrated in the present study that aged female 3×Tg-AD mice showed depression-like behavior accompanied with cognitive dysfunction. The complex and diverse mechanism appears not only relevant to the imbalance of multiple neurotransmitter pathways, including the transmitters and receptors of the monoaminergic, GABAergic, histaminergic, and cholinergic systems, but also related to the changes in L-arginine and CREB signaling molecules. [ABSTRACT FROM AUTHOR]

Gamified learning is an instructional strategy that motivates students to learn, and the use of multiple representations assists learning by promoting students' thinking and advanced mathematical problem-solving skills. In particular, emergency distance learning caused by the COVID-19 pandemic may result in a lack of motivation and effectiveness in learning. This study designed an online gamified learning activity incorporating multi-representational scaffolding and compared the differences in the learning achievement and motivation for the gamified activity and general synchronous distance learning. In addition, for the group that conducted the gamified learning activity, we measured the participants' flow, anxiety, and emotion during the activity. A total of 36 high school students participated in the experiment. The results indicated that the gamified learning activity was not significantly effective in terms of enhancing learning achievement. In terms of learning motivation, a significant decrease in motivation was found for the group using general synchronous learning, while a significant increase in motivation was found for the group using synchronous gamified learning. This indicates that despite the negative impact of the pandemic on learning, gamified learning still enhances students' learning motivation. The results of flow, anxiety, and emotion showed that the participants had a positive and engaged experience. Participants provided feedback that the multi-representational scaffolding facilitates learning. [ABSTRACT FROM AUTHOR]

Soil erosion is a prominent environmental problem in karst regions. Exploring the spatiotemporal variability of soil erosion and the factors that influence soil erosion is of great significance for regional soil erosion prevention and control. However, the mechanisms influencing the characteristic features of the karst basins, such as bedrock exposure and lithology, still need to be further explored. This study used GIS technology, the Revised Universal Soil Loss Equation model, Getis-Ord Gi*, and partial least squares regression (PLSR) to identify the dominant factors influencing soil erosion and the spatiotemporal variability of soil erosion in 31 sub-basins of the Dabang River Basin (DRB), a typical karst area of Southwest China, from 2010 to 2020. The results indicated that soil erosion in the DRB from 2010 to 2020 was generally decreasing, the mean soil erosion in the DRB in 2010, 2015 and 2020 was 18.46, 16.51 and 15.29 t ha−1 a−1, respectively. During the study period, the area of slight erosion increased by 26.39% (706.54 km2), while severe erosion enlarged by 26.36 km2. Spatially, the DRB was primarily affected by medium and slight soil erosion. The hot spot areas of soil erosion (key control areas) were mainly concentrated in the central and southern parts of the basin, decreasing each year, and the area of soil erosion hot pots has decreased from 43.22% to 20.60%. PLSR decoupling results show that elevation, bedrock exposure, land use type, interbedded limestone and clastic rock, and vegetation coverage were identified as the key variables affecting soil erosion, explaining 52.8% of soil erosion variability, with a high value of the Variable Importance on Projection (VIP) more than 1. These results can be used as a reference for comprehensive control of soil erosion and water loss in the basin. [ABSTRACT FROM AUTHOR]

Health risks from exposure to contaminants are generally estimated by evaluating concentrations of the contaminants in environmental matrixes. However, accurate health risk assessment is difficult because of uncertainties regarding exposures. This study aims to utilize data on the concentrations of organophosphate flame retardants (OPFRs) in surface soil across China coupled with Monte Carlo simulations to compensate for uncertainties in exposure to evaluate the health risks associated with contamination of soil with this class of flame retardants. Results revealed that concentrations of ∑OPFRs were 0.793-406 ng/g dry weight (dw) with an average of 23.2 ng/g dw. In terms of spatial distribution, higher OPFRs concentrations were found in economically developed regions. Although the values of health risk of OPFRs in soil across China were below the threshold, the high concentrations of OPFRs in soil in some regions should attract more attentions in future. Sensitivity analysis revealed that concentrations of OPFRs in soil, skin adherence factor, and exposure duration were the most sensitive parameters in health risk assessment. In summary, the study indicated that the national scale soil measurement could provide unique information on OPFRs exposure and health risk assessment, which was useful for the management of soil in China and for better understanding of the environmental fate of OPFRs in the global perspective. [ABSTRACT FROM AUTHOR]

Background: Sepsis-associated encephalopathy (SAE) is characterized by blood–brain barrier (BBB) disruption, neuron apoptosis and inflammation. Studies show that miR-370-3p can be a new diagnostic biomarker for SAE. Objective: This study aims to investigate the role of miR-370-3p in SAE and the underlying mechanism. Result: An in vitro model of BBB disruption was established in brain microvascular endothelial cells (BMECs) with lipopolysaccharide (LPS). The expression level of RNAs was tested via RT-qPCR. Protein levels were detected by western blotting. Annexin V/PI double staining and CCK-8 assays were conducted to assess the apoptosis and viability of brain microvascular endothelial cells (BMECs). The migration of BMECs was detected by Transwell assay. BBB permeability analysis was performed to assess the relative permeability coefficient of BMECs. The in vitro barrier integrity was detected by trans-epithelial/endothelial electrical resistance (TEER). The binding between miR-370-3p and SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) was identified by luciferase reporter assay. In this study, miR-370-3p was upregulated in LPS-treated BMECs. MiR-370-3p knockdown alleviated LPS-induced BBB disruption and apoptosis of BMECs, as well as recovered cell viability and migration. SMURF1 was directly targeted by miR-370-3p. SMURF1 silencing reversed the effects of miR-370-3p deficiency in LPS-stimulated BMECs. Moreover, miR-370-3p activated the TLR4/MyD88/NF-κB signaling via regulating SMURF1 in LPS-stimulated BMECs. Conclusion: MiR-370-3p aggravates BBB disruption and neuron apoptosis by targeting SMURF1 to activate the TLR4/MyD88/NF-κB signaling in SAE. [ABSTRACT FROM AUTHOR]

Formyl peptide receptor-like 1 inhibitor protein (FLIPr) is an immune evasion protein produced by Staphylococcus aureus, and FLIPr is a potential vaccine candidate for reducing Staphylococcus aureus virulence and biofilm formation. We produced recombinant lipidated FLIPr (rLF) to increase the immunogenicity of FLIPr and showed that rLF alone elicited potent anti-FLIPr antibody responses to overcome the FLIPr-mediated inhibition of phagocytosis. In addition, rLF has potent immunostimulatory properties. We demonstrated that rLF is an effective adjuvant. When an antigen is formulated with rLF, it can induce long-lasting antigen-specific immune responses and enhance mucosal and systemic antibody responses as well as broad-spectrum T-cell responses in mice. These findings support further exploration of rLF in the clinic as an adjuvant for various vaccine types with extra benefits to abolish FLIPr-mediated immunosuppressive effects. [ABSTRACT FROM AUTHOR]

This letter to the editor responds to a study on the risk factors of knee reinjury after anterior cruciate ligament (ACL) reconstruction. The authors suggest that the study could benefit from further elaboration and clarity in several areas. They emphasize the importance of detailed information on rehabilitation protocols, as standardized and evidence-based protocols are crucial for minimizing reinjury risk. The authors also highlight the need to consider psychological aspects, such as fear of sports and psychological readiness to return to sports, as these factors interact with knee symptoms and may influence reinjury risks. They recommend incorporating objective assessment tools, such as in-person evaluations and advanced imaging techniques, to provide more reliable data on knee function and reinjury. Overall, the authors believe that by addressing these areas, future research can enhance the effectiveness of ACL reconstruction management strategies. [Extracted from the article]

Purpose: Language networks are reorganized during glioma growth, leading to varying language performance in patients with gliomas located in or around language-eloquent areas. Therefore, pre-treated language performance reflects the neuroplasticity potential. Different domains of language processing, such as speech expression, repetition, and comprehension, involving different neural networks. We analyzed the effects of patient factors and tumor characteristics on the pre-treated performance to investigate neuroplastic potential of different language domains. Methods: Patient age, sex, education level, tumor grade, language pathway involvement, T1 contrast enhanced (C+), and FLAIR (T2) volume were selected as variables. The correlation with abnormal language performance was verified using univariate and multivariate logistic regression. Results: In total, 104 left hemispheric glioma patients were enrolled in this study. 44% of patients had repetitive abnormalities, 34.9% had comprehensive abnormalities, and 32.1% had expressive abnormalities. The proportion of normal language performance was 60% in grade 2 and 3 gliomas and 16% in grade 4 gliomas. Tumor grade (p = 0.006) and T2 volume (p = 0.008) were associated with abnormal performance in the expressive domain, education level (p = 0.004) and T1 C+ volume (p = 0.049) in the repetitive domain, and education level (p = 0.013), T2 volume (p = 0.011), and tumor grade (p = 0.089) in the comprehensive domain. Conclusion: Different clinical and radiological factors affected the abnormal performance of the three language domains, indicating their functional connectivity and neuroplastic potential are inherently varied. The dynamic interactions between patient factors, tumor characteristics, and language processing should be considered when resecting left hemispheric gliomas. [ABSTRACT FROM AUTHOR]

Herein, we analyzed total polyphenol content, total flavonoid content, and the antioxidant activity of the ethanol and distilled water extracted Houttuynia cordata perennial herb. Later, we investigated the possibility of producing Houttuynia cordata extract (HCE) loaded Polyurethane (PU) nanofibers via the electrospinning technique. The analysis confirmed that the total polyphenol, total flavonoid content, and antioxidant activity of the ethanol extracted HCE were higher than the distilled water extracted HCE. Therefore, the ethanol extracted HCE was used to prepare HCE/PU nanofibers by varying concentrations of HCE and PU. The HCE/PU nanofibers showed a mixed pattern of beads and fibers at a PU concentration of 10 wt%. However, at 12 wt% PU concentration, relatively uniform nanofibers with an average diameter of about 200 nm were formed at 1.0% and 1.5 wt% of HCE. The successful incorporation of HCE in PU nanofibrous matrix was confirmed by the presence of its characteristic bands in Fourier transform infrared (FTIR) and X-ray diffraction (XRD) spectra. The addition of HCE increased the crystallinity, the amount of heat required for pyrolysis, and the thermal stability of HCE/PU nanofibers, which must be credited to the HCE-derived quercitrin and quercetin crystallite solids. [ABSTRACT FROM AUTHOR]

The oral and craniofacial region consists of various types of hard and soft tissues with the intricate organization. With the high prevalence of tissue defects in this specific region, it is highly desirable to enhance tissue regeneration through the development and use of engineered biomaterials. Collagen, the major component of tissue extracellular matrix, has come into the limelight in regenerative medicine. Although collagen has been widely used as an essential component in biomaterial engineering owing to its low immunogenicity, high biocompatibility, and convenient extraction procedures, there is a limited number of reviews on this specific clinic sector. The need for mechanical enhancement and functional engineering drives intensive efforts in collagen-based biomaterials concentrating on therapeutical outcomes and clinical translation in oral and craniofacial tissue regeneration. Herein, we highlighted the status quo of the design and applications of collagen-based biomaterials in oral and craniofacial tissue reconstruction. The discussion expanded on the inspiration from the leather tanning process on modifications of collagen-based biomaterials and the prospects of multi-tissue reconstruction in this particular dynamic microenvironment. The existing findings will lay a new foundation for the optimization of current collagen-based biomaterials for rebuilding oral and craniofacial tissues in the future. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a health-threatening neurodegenerative disease of the elderly with clinical manifestations of motor and non-motor deficits such as tremor palsy and loss of smell. Alpha-synuclein (α-Syn) is the pathological basis of PD, it can abnormally aggregate into insoluble forms such as oligomers, fibrils, and plaques, causing degeneration of nigrostriatal dopaminergic neurons in the substantia nigra in the patient's brain and the formation of Lewy bodies (LBs) and Lewy neuritis (LN) inclusions. As a result, achieving α-Syn aggregate detection in the early stages of PD can effectively stop or delay the progression of the disease. In this paper, we provide a brief overview and analysis of the molecular structures and α-Syn in vivo and in vitro detection methods, such as mass spectrometry, antigen–antibody recognition, electrochemical sensors, and imaging techniques, intending to provide more technological support for detecting α-Syn early in the disease and intervening in the progression of Parkinson's disease. [ABSTRACT FROM AUTHOR]

Purpose: To explore the position change of fetal conus medullaris by ultrasound, and to propose gestational age-specific references for the lower limits of fetal conus medullaris level. Methods: We prospectively collected the imaging and clinical data of fetuses whose mothers accepted routine prenatal ultrasonic follow-ups in the Department of Medical Ultrasonics, Chinese PLA General Hospital, between November 2020 and April 2021. By assigning to the conus medullaris levels, calculating statistical data, and performing linear regression analysis, we determined the correlation between the conus medullaris level and gestational week, as well as between the 95th percentile of the conus medullaris level, i.e., the lower limit of the conus medullaris level, and gestational week. Results: We included 1202 different fetuses at 17–40 gestational weeks in the study. Both the conus medullaris level and the 95th percentile of the conus medullaris level were linearly correlated with gestational week. We calculated the adjusted values of the lower limits of fetal conus medullaris levels, that is, the theoretical references of the lower limits, according to the linear regression equation, and composed a comparison table. Conclusion: The fetal conus medullaris position continues changing cranially with gestational weeks during the whole pregnancy. The conus medullaris of a term fetus should not lie below the L2 vertebra level at birth. We proposed reference criteria of fetal low-lying conus medullaris for each gestational week from 17 to 40 weeks of gestational age, which potentially help prompt diagnosis and improve prognosis of fetal tethered cord syndrome. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer among women worldwide. Studies have reported minimal birth cohort effects on the incidence rates of breast cancer in Western countries but have reported notable birth cohort effects in some Asian countries. The risks of breast cancer may also vary within a country. In the present study, we abstracted female invasive breast cancer data from the Taiwan Cancer Registry for the period 1997–2016. We used the age–period–cohort model to compare birth cohort effects on breast cancer incidence rates between urban and rural regions in Taiwan. We identified a notable urban–rural disparity in birth cohort effects on breast cancer incidence rates in women in Taiwan. The incidence rates in the urban regions were higher than those in the rural regions across all cohorts. However, the incidence rates rose faster in the rural regions than in the urban regions across the cohorts. The risks of breast cancer observed for women born in 1992 were approximately 22 and 11 times than those observed for women born in 1917 in rural and urban regions, respectively. The observed gap in breast cancer incidence rates between the urban and rural regions gradually disappeared across the cohorts. Accordingly, we speculate that urbanization and westernization in Taiwan may be the drivers of female breast cancer incidence rates across birth cohorts. [ABSTRACT FROM AUTHOR]

The incidence rate of cardiovascular diseases (CVDs) remains high, and their mortality rate is significantly higher than that of other diseases. Growth differentiation factor-15 (GDF-15) is a recently developed biomarker for the early diagnosis and prognostic evaluation of CVDs because its concentration in serum increases substantially after a cardiovascular injury or an inflammatory reaction. In this study, a sandwich-type immunosensor was constructed for the sensitive detection of GDF-15. Specifically, peony-like zinc gallinate (ZnGa2O4) prepared using a hydrothermal method, which exhibits excellent electrocatalytic performance, was coupled with Au nanoparticles (NPs) to obtain golden-peony-like ZnGa2O4/Au NPs. They preserved the immune activity of GDF-15 antibody molecules and further enhanced the conductivity, thereby realizing additional signal amplification. Hollow polyaniline (PANI) microtubules decorated with Pd NPs were used as the sensing platform (PANI/Pd NPs). The hollow microtubules provided abundant active sites and considerably improved the electron-transfer rate. Under optimal conditions, a linear range and remarkably low detection limit of 100 fg mL−1–10 ng mL−1 and 42.23 fg mL−1, respectively, were achieved. These experimental results indicate that the strategy reported herein can be adopted as a novel approach for the convenient and rapid detection of GDF-15. [ABSTRACT FROM AUTHOR]

As one of the most significant factors for mobile users, continuous locations have been considered in associating with destination in location-based services. In this paper, we consider the destination associated with each location in moving and design an association shifting scheme (ASS) to enhance mobile user's location privacy. Specifically, we first formalize the model of associating destination with continuous locations such that we can quantify the association. Then we evaluate the model of destination associating with some algorithms. To address this association, we design ASS, which consists of three algorithms that termed as the location shifting algorithm (LSA), the destination constraint algorithm (DCA) and the shifted destination association algorithm (SDAA). In LSA, we shift the real location into a location without association to precise destination, based on the properties of mutual information, which preserves the concealment of precise destination. In DCA, we utilize probability indistinguishable which is a feature inherited from differential privacy to constrain the shifting location, and guides this location to a fake destination with similar probabilities. In SDAA, we leverage the correlation coefficient to map the shifted destination, which helps users to choose fake destination far away from the real one. Moreover, we discuss the security properties of our scheme. We have conducted real experiments on real-world data sets. Experimental results show that our scheme out performs existing approaches in effectiveness and efficiency. [ABSTRACT FROM AUTHOR]

Fostering students' competence in applying interdisciplinary knowledge to solve problems has been recognized as an important and challenging issue globally. This is why STEM (Science, Technology, Engineering, Mathematics) education has been emphasized at all levels in schools. Meanwhile, the use of robotics has played an important role in STEM learning design. The purpose of this study was to fill a gap in the current review of research on Robotics-based STEM (R-STEM) education by systematically reviewing existing research in this area. This systematic review examined the role of robotics and research trends in STEM education. A total of 39 articles published between 2012 and 2021 were analyzed. The review indicated that R-STEM education studies were mostly conducted in the United States and mainly in K-12 schools. Learner and teacher perceptions were the most popular research focus in these studies which applied robots. LEGO was the most used tool to accomplish the learning objectives. In terms of application, Technology (programming) was the predominant robotics-based STEM discipline in the R-STEM studies. Moreover, project-based learning (PBL) was the most frequently employed learning strategy in robotics-related STEM research. In addition, STEM learning and transferable skills were the most popular educational goals when applying robotics. Based on the findings, several implications and recommendations to researchers and practitioners are proposed. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) consists of a group of hematologic tumors that are derived from the clonal proliferation of hematopoietic stem cells, featuring abnormal hematopoietic cell development and ineffective hematopoiesis. Animal models are an important scientific research platform that has been widely applied in the research of human diseases, especially tumors. Animal models with MDS can simulate characteristic human genetic variations and tumor phenotypes. They also provide a reliable platform for the exploration of the pathogenesis and diagnostic markers of MDS as well as for a drug efficacy evaluation. This paper reviews the research status of three animal models and a new spontaneous mouse model with MDS. [ABSTRACT FROM AUTHOR]

Clean and sustainable H2 production is crucial to a carbon–neutral world. H2 generation by Chlamydomonas reinhardtii is an attractive approach for solar-H2 from H2O. However, it is currently not large-scalable because of lacking desirable strains with both optimal H2 productivity and sufficient knowledge of underlying molecular mechanism. We hereby carried out extensive and in-depth investigations of H2 photoproduction of hpm91 mutant lacking PGR5 (Proton Gradient Regulation 5) toward its up-scaling and fundamental mechanism issues. We show that hpm91 is at least 100-fold scalable (up to 10 L) with continuous H2 collection of 7287 ml H2/10L-HPBR in averagely 26 days under sulfur deprivation. Also, we show that hpm91 is robust and active during sustained H2 photoproduction, most likely due to decreased intracellular ROS relative to wild type. Moreover, we obtained quantitative proteomic profiles of wild type and hpm91 at four representing time points of H2 evolution, leading to 2229 and 1350 differentially expressed proteins, respectively. Compared to wild type, major proteome alterations of hpm91 include not only core subunits of photosystems and those related to anti-oxidative responses but also essential proteins in photosynthetic antenna, C/N metabolic balance, and sulfur assimilation toward both cysteine biosynthesis and sulfation of metabolites during sulfur-deprived H2 production. These results reveal not only new insights of cellular and molecular basis of enhanced H2 production in hpm91 but also provide additional candidate gene targets and modules for further genetic modifications and/or in artificial photosynthesis mimics toward basic and applied research aiming at advancing solar-H2 technology. [ABSTRACT FROM AUTHOR]

In this work, perovskite solar cells (PSCs) with different transport layers were fabricated to understand the hysteresis phenomenon under a series of scan rates. The experimental results show that the hysteresis phenomenon would be affected by the dielectric constant of transport layers and scan rate significantly. To explain this, a modified Poisson and drift-diffusion solver coupled with a fully time-dependent ion migration model is developed to analyze how the ion migration affects the performance and hysteresis of PSCs. The modeling results show that the most crucial factor in the hysteresis behavior is the built-in electric field of the perovskite. The non-linear hysteresis curves are demonstrated under different scan rates, and the mechanism of the hysteresis behavior is explained. Additionally, other factors contributing to the degree of hysteresis are determined to be the degree of degradation in the perovskite material, the quality of the perovskite crystal, and the materials of the transport layer, which corresponds to the total ion density, carrier lifetime of perovskite, and the dielectric constant of the transport layer, respectively. Finally, it was found that the dielectric constant of the transport layer is a key factor affecting hysteresis in perovskite solar cells. [ABSTRACT FROM AUTHOR]

Monitoring and evaluating the evolution of rocky desertification timely and studying the characteristics of soil erosion under different rainfall patterns are of great scientific significance for regional soil and water conservation, rocky desertification control and ecological environment construction. Four periods of remote sensing image data from 2005 to 2020 were selected to study the evolution characteristics of rocky desertification and its impact on soil erosion in the controlled boundary area of Shibantang hydrological station of Yeji River Watershed, Guizhou Province, China. According to the 408 erosive rainfall events, the soil erosion under different rainfall patterns in the watershed was analyzed. The results showed that: erosive rainfall events in the study area were mainly pattern A, accounting for 57.4% of the total rainfall events; the second was pattern B, accounting for 28.9% of the total rainfall events; the rainfall pattern of C occurred occasionally. Among them, pattern A was the main rainfall pattern leading to soil and water loss and had the largest contribution rate to soil erosion in the watershed. From 2005 to 2020, the area of rocky desertification showed a decreasing trend, accounting for 72.2% from 87.9%. Spatially, rocky desertification has mainly concentrated in the middle south of the watershed since 2010, while the rocky desertification mainly concentrated in the middle and north before 2010. The effects of different grades of rocky desertification on soil erosion were different, and the soil erosion modulus in areas with the medium, severe and extremely severe rocky desertification was generally small. The soil erosion modulus estimated by the RUSLE (Revised Universal Soil Loss Equation) model was still much higher than that calculated by the data measured by the hydrological monitoring station. Therefore, the application of the RUSLE model in karst area needs to be further modified. These results can provide reference for rocky desertification control, soil erosion control and fragile ecosystem restoration in karst area. [ABSTRACT FROM AUTHOR]

Learning a new language is a major challenge faced by many forced migrants. Current vocabulary learning curricula are not adapted to the migrants' needs, which makes the learning process even more challenging. Today, the widespread use of smartphones among forced migrants provides us with new opportunities to collect and recommend the vocabulary they need. In this work, we propose a demographic- and content-based vocabulary recommendation approach that considers the migrant's status, migration stage, and vocabulary themes. Based on our approach, the vocabulary recommended to a forced migrant belongs to the same theme as the vocabulary that other forced migrants in the same migration stage chose to learn. The approach was evaluated with 37 Syrian refugees in Lebanon and Germany that used SCROLL, an informal language learning tool, to learn their target language. We compared the learning achievement and motivation of the participants when they learned the recommended vocabulary and the standard textbook vocabulary. Our results showed that the proposed vocabulary recommendation approach resulted in higher learning achievement for refugees in Germany and higher motivation levels for refugees in Germany and Lebanon. Tailored vocabulary recommendation approaches showed potential to improve the language learning experience of forced migrants and warrant further study. [ABSTRACT FROM AUTHOR]

Primary liver cancer is a heterogeneous disease in terms of its etiology, histology, and therapeutic response. Concurrent proteomic and genomic characterization of a large set of clinical liver cancer samples can help elucidate the molecular basis of heterogeneity and thus serve as a valuable resource for personalized liver cancer treatment. In this study, we perform proteomic profiling of ~300 proteins on 259 primary liver cancer tissues with reverse-phase protein arrays, mutational analysis using whole genome sequencing and transcriptional analysis with RNA-Seq. Patients are of Japanese ethnic background and mainly HBV or HCV positive, providing insight into this important liver cancer subtype. Unsupervised classification of tumors based on protein expression profiles reveal three proteomic subclasses R1, R2, and R3. The R1 subclass is immunologically hot and demonstrated a good prognosis. R2 contains advanced proliferative tumor with TP53 mutations, high expression of VEGF receptor 2 and the worst prognosis. R3 is enriched with CTNNB1 mutations and elevated mTOR signaling pathway activity. Twenty-two proteins, including CDK1 and CDKN2A, are identified as potential prognostic markers. The proteomic classification presented in this study can help guide therapeutic decision making for liver cancer treatment. The molecular heterogeneity of primary liver cancer remains to be characterised. Here, the authors perform multi-omics analysis of 259 primary liver cancer tissues and identify three distinct molecular subtypes. [ABSTRACT FROM AUTHOR]

Mathematical modeling is a high-leverage topic, critical for college and career readiness, participation in STEM education, and civic engagement. Mathematical modeling involves connecting real-world situations, phenomenon, and/or data with mathematical models, and in this way applies across various STEM disciplines, including mathematics, engineering, and science. Although research has begun to explore mathematical modeling instruction in the elementary grades, questions remain about how to assess student learning at the elementary level. We addressed this need by designing an assessment of mathematical modeling competencies for students in grades 3 through 5. Informed by international research, our assessment includes a hybrid structure to assess mathematical modeling competencies holistically (as students engage in the complete modeling process) and atomistically (as students engage in different components of the modeling process, including making sense of phenomena and real-world situations, setting up and operating on mathematical models, and interpreting results in relation to the real-world context). We conducted student interviews, followed by two rounds of pilot testing to inform item development and ensure acceptable psychometric properties. The final assessment included 13 items (9 multiple choice, 3 open-response, and 1 complete modeling task). We describe our assessment development process, and provide sample assessment items and detailed coding rubrics. We summarize quantitative analyses which established high reliability and low standard error for our assessment, supporting its use for grades 3 to 5. Implications of our framework and assessment for mathematical modeling instruction and future research on STEM learning are discussed. [ABSTRACT FROM AUTHOR]

After 24 h of seeding, zerumbone (5, 10, and 20 g/mL), zerumbone epoxide (5, 10, and 20 g/mL) or glucosamine (100 g/mL) were diluted with the culture medium to different concentrations and added to the cultured cells and then were incubated for another 24 h. The SW1353 chondrosarcoma cells were cultured with increasing concentrations of zerumbone, zerumbone epoxide (5, 10 or 20 g/mL), or glucosamine (100 g/mL) for 24 h, followed by AlmarBlue analysis. At 20 g/mL, zerumbone significantly reduced MMP-1 production to 2.98 ± 0.14 ng/mL ( I p i < 0.01), the 20 g/mL zerumbone epoxide reduced MMP-1 production to 3.15 ± 0.94 pg/mL compare to the IL-1 alone-treated group, respectively. The SW1353 cells were pretreated with various concentrations of zerumbone, zerumbone epoxide (5, 10, and 20 g/mL), or glucosamine (100 g/mL) for 1 h, then stimulated with or without IL-1 (10 ng/mL) for 24 h. [Extracted from the article]