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Critical thinking is important for higher education yet challenging to teach. Despite much research and conceptual analysis, the practice of teaching remains both difficult and contested. Studies often draw on the experiences of teachers, or research by teachers on student experiences. Here, we argue that student voice in critical thinking research has not received enough attention and that student perspectives can contribute to its theories of teaching and learning. The research was conducted by three undergraduate authors and examine what fellow students had to say about developing critical thinking. An empirical model emerged that showed how flexibility in learning objectives could describe critical thinking development in relation to how much space is left for students to take charge of their own learning. We conclude with the idea of focused dialogue between teachers and students, and in particular among teachers themselves, in order to organise curriculum experiences for critical thinking.

Abstract CD8+ T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8+ T cells. Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8+ T cells. T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8+ T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8+ T cells through cleavage of membrane CD122. ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8+ T cells. Intriguingly, inhibition of ADAM17 in CD8+ T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumors. Our findings reveal a critical post-translational regulation in CD8+ T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

Abstract Background Accurate segmentation of gastric tumors from CT scans provides useful image information for guiding the diagnosis and treatment of gastric cancer. However, automated gastric tumor segmentation from 3D CT images faces several challenges. The large variation of anisotropic spatial resolution limits the ability of 3D convolutional neural networks (CNNs) to learn features from different views. The background texture of gastric tumor is complex, and its size, shape and intensity distribution are highly variable, which makes it more difficult for deep learning methods to capture the boundary. In particular, while multi-center datasets increase sample size and representation ability, they suffer from inter-center heterogeneity. Methods In this study, we propose a new cross-center 3D tumor segmentation method named Hierarchical Class-Aware Domain Adaptive Network (HCA-DAN), which includes a new 3D neural network that efficiently bridges an Anisotropic neural network and a Transformer (AsTr) for extracting multi-scale context features from the CT images with anisotropic resolution, and a hierarchical class-aware domain alignment (HCADA) module for adaptively aligning multi-scale context features across two domains by integrating a class attention map with class-specific information. We evaluate the proposed method on an in-house CT image dataset collected from four medical centers and validate its segmentation performance in both in-center and cross-center test scenarios. Results Our baseline segmentation network (i.e., AsTr) achieves best results compared to other 3D segmentation models, with a mean dice similarity coefficient (DSC) of 59.26%, 55.97%, 48.83% and 67.28% in four in-center test tasks, and with a DSC of 56.42%, 55.94%, 46.54% and 60.62% in four cross-center test tasks. In addition, the proposed cross-center segmentation network (i.e., HCA-DAN) obtains excellent results compared to other unsupervised domain adaptation methods, with a DSC of 58.36%, 56.72%, 49.25%, and 62.20% in four cross-center test tasks. Conclusions Comprehensive experimental results demonstrate that the proposed method outperforms compared methods on this multi-center database and is promising for routine clinical workflows.

Abstract Background There is an unmet need for precise biomarkers for early non-invasive breast cancer detection. Here, we aimed to identify blood-based DNA methylation biomarkers that are associated with breast cancer. Methods DNA methylation profiling was performed for 524 Asian Chinese individuals, comprising 256 breast cancer patients and 268 age-matched healthy controls, using the Infinium MethylationEPIC array. Feature selection was applied to 649,688 CpG sites in the training set. Predictive models were built by training three machine learning models, with performance evaluated on an independent test set. Enrichment analysis to identify transcription factors binding to regions associated with the selected CpG sites and pathway analysis for genes located nearby were conducted. Results A methylation profile comprising 51 CpGs was identified that effectively distinguishes breast cancer patients from healthy controls achieving an AUC of 0.823 on an independent test set. Notably, it outperformed all four previously reported breast cancer-associated methylation profiles. Enrichment analysis revealed enrichment of genomic loci associated with the binding of immune modulating AP-1 transcription factors, while pathway analysis of nearby genes showed an overrepresentation of immune-related pathways. Conclusion This study has identified a breast cancer-associated methylation profile that is immune-related to potential for early cancer detection.

The construction of 14 large-scale coal bases and 89 demonstration bases for the comprehensive utilization of bulk solid waste in China marks that the utilization of bulk solid waste in mining areas has been incorporated into the national strategic development layout. The long-term high-intensity development and utilization of coal resources has caused the near depletion of shallow-buried coal seam resources in mining areas, and the large-scale solid waste accumulation and surface subsidence of coal power and chemical bases has become a problem restricting the green, low-carbon and high-quality development of mining areas. Co-operative utilization of bulk coal-based solid waste and green filling is an effective way to liberate the “three down and one up” pressed coal, extend the service life of mines, and realize the harmless, resourceful, and large-scale “three” utilization of solid waste. Based on the types and production of coal-based solid waste in Shanxi Province, the “East China Energy Granary” Anhui Lianghuai Base and Ningdong Energy and Chemical Base, it elaborates in detail the harmless disposal of coal-based solid waste through heavy metal adsorption and desorption and complexation passivation technology with coal gangue, fly ash, furnace slag, gasification slag and desulphurization gypsum as the main materials, listing the classification and application of coal-based solid waste, and the application of coal gangue, fly ash, furnace slag, gasification slag and desulphurization gypsum as the main materials. List the ways of resource utilization of coal-based solid waste classified and applied to low calorific value coal-based solid waste for power generation, preparation of building materials such as cement, bricks and tiles, etc. Comparatively analyze the ways of reclamation and backfilling of coal mining subsidence area and downhole filling and large-scale utilization of coal-based solid waste, highlighting the superiority of downhole filling of coal-based solid waste. Based on the deep coal resources of coal electrification bases, the theory and key technologies of green filling mining are proposed, including the synergistic technology of deep coal gangue source reduction and mining and filling, the technology of efficient preparation and deep underground transportation of filling materials, and the deep multi-field coupling mechanism of coal-based solid waste filling materials, and the technological principles and methods of the whole process of deep filling mining of multi-source coal-based solid waste from the source, process to the end are investigated to solve the technical problems of deep underground filling of mining areas. The technical problems of filling are solved. According to the geological conditions and filling purposes of Renjiazhuang Coal Mine in Ningdong Base, Huoerxinhe Coal Mine in Shanxi Province and Huaibei Mining Area, the key technologies of low-level filling by overdrilling, multi-separation layer stepped grouting under the conditions of atypical characteristics of key layers and synergistic utilization of coal-based solid wastes have been proposed, which comprehensively combine the advantages of disposal and utilization of solid wastes from mines, development and utilization of deep coal resources, control of subsidence of the ground surface, and ecological environment protection, and form a comprehensive plan for the disposal and utilization of bulk solid wastes from coal power and chemical bases. Coal power and chemical base bulk solid waste synergistic utilization and green mining mode, providing reference for high quality coal mining and low damage to the environment.

The Western Route of the South-to-North Water Diversion Project is the final link to be constructed for the four-horizontal three-vertical framework of China’s national water network. The adjustable water volume in the water source areas is a focal and challenging issue in the planning and demonstration of the Western Route. This study raised ten questions related to the adjustable water volume in the water source areas of the Western Route from the aspects of water resource background conditions and evolution trends, ecological and socio-economic water demands, scales of reservoirs and water conveyance projects, as well as impacts of water diversion on water resource development and utilization, aquatic ecological environment, hydropower, and navigation in the water source areas and their lower reaches. Based on a distributed hydrological model of the upper reaches of the Yangtze River, a simulation and analysis model for calculating the adjustable water volume in water source areas of the Western Route is established to quantitatively answer the ten questions raised. The main conclusions are as follows. First, under the premise of solely satisfying ecological and socio-economic water demands within and outside the river channels of the water source areas, a plan that combines upper and lower routes presents an average adjustable water volume of 1.59×1010 m³ over multiple years, while a plan for solely constructing a lower route can reach an average adjustable water volume of 1.74×1010 m³ by constructing the Gangtuo Reservoir for coordinated operation. Second, comprehensively considering the impacts of water diversion on water balance, hydropower, and navigation, as well as their acceptability in the water source areas, the adjustable water volume is between 1.22×1010 and 1.26×1010 m³. Third, in the long term, the plan should focus on connecting and integrating the water network in the southwestern region with the main framework and major streams of the national water network of China. This will reduce the impacts of water diversion by the Western Route Project, increase the overall water supply capacity of the project, and promote its adaptability to external conditions such as climate change.

Abstract Background Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels. Methods Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Result The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p

Background Autoimmune thyroiditis is closely associated with major depressive disorder (MDD) and suicide attempts. However, few studies have examined this relationship. Aims The study aimed to assess the prevalence and correlates of suicide attempts in patients with first-episode drug-naïve (FEDN) MDD and autoimmune thyroiditis. Method We recruited 1718 out-patients with FEDN MDD and assessed depressive, anxiety and psychotic symptoms with the Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety (HRSA) and Positive and Negative Syndrome Subscale positive subscale, respectively. The serum levels of free triiodothyronine, free thyroxine, thyroid stimulating hormone (TSH), antithyroglobulin, thyroid peroxidase antibody (TPOAb) and several other metabolic parameters were assessed. Patients were divided into non-autoimmune thyroiditis, autoimmune thyroiditis only and autoimmune thyroiditis with abnormal TSH groups, based on autoimmune thyroiditis severity. Multiple logistic regression model was applied to identify the correlates of suicide attempts in patients with MDD and autoimmune thyroiditis with abnormal TSH. Results Compared with the non-autoimmune thyroiditis group, the autoimmune thyroiditis with abnormal TSH group had a nearly fourfold higher likelihood of reporting a suicide attempt, whereas no difference was found between the non-autoimmune thyroiditis and autoimmune thyroiditis only groups. HRSA score, lnTPOAb and lnTSH were independently associated with suicide attempts in patients with autoimmune thyroiditis with abnormal TSH. Conclusions Patients with MDD and autoimmune thyroiditis with abnormal TSH are at higher risk for suicide attempt. TPOAb, TSH and anxiety are all independently associated with suicide attempts in this population, and regular thyroid checks are warranted.

Abstract The reduction of non‐gravitational accelerations through an onboard accelerometer is a vital part of accurately estimating gravity fields for Gravity Recovery and Climate Experiment (GRACE) Follow‐On (GRACE‐FO). Current accelerometer quality, specifically a defect on the GRACE‐D accelerometer, necessitates the use of extensive calibration techniques to optimally utilize the accelerometer measurements. This paper describes these techniques and correction algorithms as they are used for the official GRACE‐FO accelerometer products, which rest on the information present in the partially functional GRACE‐D accelerometer. First, transplanted data from GRACE‐C is used to remove common effects between the spacecraft. Then, GRACE‐D data is utilized to compute a correction to the transplanted data to account for solar radiation pressure (SRP) and albedo using a parity argument and to account for non‐common drag and thruster leaks in the attitude control system. The SRP and albedo term predominantly improves C3,0 while the drag and leaky thruster term improves the gravity field across the entire spectrum. Finally, some comments on alternative data usage, initial modifications to the algorithms to account for other spacecraft operational modes, and future outlook are provided.

Estimating the carbon sequestration potential of Moso bamboo (Phyllostachys pubescens) forests and optimizing management strategies play pivotal roles in enhancing quality and promoting sustainable development. However, there is a lack of methods to simulate changes in carbon sequestration capacity in Moso bamboo forests and to screen and optimize the best management measures based on long-term time series data from fixed-sample fine surveys. Therefore, this study utilized continuous survey data and climate data from fixed sample plots in Zhejiang Province spanning from 2004 to 2019. By comparing four different algorithms, namely random forest, support vector machine, XGBoost, and BP neural network, to construct aboveground carbon stock models for Moso bamboo forests. The ultimate goal was to identify the optimal algorithmic model. Additionally, the key driving parameters for future carbon stocks were considered and future aboveground carbon stocks were predicted in Moso bamboo forests. Then formulated an optimal management strategy based on these predictions. The results indicated that the carbon stock model constructed using the XGBoost algorithm, with an R2 of 0.9895 and root mean square error of 0.1059, achieved the best performance and was considered the optimal algorithmic model. The most influential driving parameters for vegetation carbon stocks in Moso bamboo forests were found to be mean age, mean diameter at breast height, and mean culm density. Under optimal management measures, which involve no harvesting of 1–3 du bamboo, 30% harvesting of 4 du bamboo, and 80% harvesting of bamboo aged 5 du and above. Our predictions show that aboveground carbon stocks in Moso bamboo forests in Zhejiang Province will peak at 36.25 ± 8.47 Tg C in 2046 and remain stable from 2046 to 2060. Conversely, degradation is detrimental to the long-term maintenance of carbon sequestration capacity in Moso bamboo forests, resulting in a peak aboveground carbon stock of 29.50 ± 7.49 Tg C in 2033, followed by a continuous decline. This study underscores the significant influence of estimating carbon sequestration potential and optimizing management decisions on enhancing and sustaining the carbon sequestration capacity of Moso bamboo forests.

Abstract Background Blood-based DNA methylation has shown great promise as a biomarker in a wide variety of diseases. Studies of DNA methylation in blood often utilize samples which have been cryopreserved for years or even decades. Therefore, changes in DNA methylation associated with long-term cryopreservation can introduce biases or otherwise mislead methylation analyses of cryopreserved DNA. However, previous studies have presented conflicting results with studies reporting hypomethylation, no effect, or even hypermethylation of DNA following long-term cryopreservation. These studies may have been limited by insufficient sample sizes, or by their profiling of methylation only on an aggregate global scale, or profiling of only a few CpGs. Results We analyzed two large prospective cohorts: a discovery (n = 126) and a validation (n = 136) cohort, where DNA was cryopreserved for up to four years. In both cohorts there was no detectable change in mean global methylation across increasing storage durations as DNA. However, when analysis was performed on the level of individual CpG methylation both cohorts exhibited a greater number of hypomethylated than hypermethylated CpGs at q-value

Abstract Miscanthus spp. show excellent application prospects due to its bioenergy potential and multiple ecological services. Annual N export with biomass harvest from Miscanthus, even without fertilizer supplement, do not reduce soil N levels. The question arises regarding how Miscanthus can maintain stable soil N levels. Metagenomic strategies were used to reveal soil N‐cycling‐related microbiome and their functional contributions to processes of soil N‐cycling based on the comparison among the bare land, cropland, 10‐year Miscanthus × giganteus, and 15‐year Miscanthus sacchariflorus fields. The results showed that, after long‐term cropland‐to‐Miscanthus conversion (LCMC), 16 of 21 bacterial phyla and all the archaeal phyla exhibited significant changes. Soil microbial denitrification and nitrification functions were significantly weakened, and N fixation (NF) was significantly enhanced. The biosynthesis of amino acids, especially alanine, aspartate, and glutamate metabolism, in soil N‐cycling‐related microbiome was dramatically promoted. The genus Anaeromyxobacter contributed largely to the NF process after LCMC. Variations in the soil available potassium, available N, organic C, and total N contents drove a functional shift of soil microbiome from cropland to Miscanthus pattern. We conclude that Miscanthus can recruit Anaeromyxobacter communities to enhance NF benefiting its biomass sustainability and soil N balance.

Rechargeable potassium ion batteries have long been regarded as one alternative to conventional lithium ion batteries because of their resource sustainability and cost advantages. However, the compatibility between anodes and electrolytes remains to be resolved, impeding their commercial adoption. In this work, the K-ion storage properties of Bi nanoparticles encapsulated in N-doped carbon nanocomposites have been examined in two typical electrolyte solutions, which show a significant effect on potassium insertion/removal processes. In a KFSI-based electrolyte, the N-C@Bi nanocomposites exhibit a high specific capacity of 255.2 mAh g−1 at 0.5 A g−1, which remains at 245.6 mAh g−1 after 50 cycles, corresponding to a high capacity retention rate of 96.24%. In a KPF6-based electrolyte, the N-C@Bi nanocomposites show a specific capacity of 209.0 mAh g−1, which remains at 71.5 mAh g−1 after 50 cycles, corresponding to an inferior capacity retention rate of only 34.21%. Post-investigations reveal the formation of a KF interphase derived from salt decomposition and an intact rod-like morphology after cycling in K2 electrolytes, which are responsible for better K-ion storage properties.

BackgroundAutoimmune thyroid disease (AITD) is the main cause of hypothyroidism in women of childbearing age. Bisphenol A (BPA) is an environmental factor affecting AITD. This study aims to investigate relationship between BPA and AITD in women of childbearing age, thereby contributing novel evidence for the prevention of hypothyroidism in this specific demographic.MethodsA total of 155 women of childbearing age were enrolled in this study, including the euthyroid group comprised 60 women with euthyroidism and thyroid autoantibodies negativity and the AITD group consisted of 95 women with euthyroidism and at least one thyroid autoantibody positivity. The general information, thyroid function, thyroid autoantibodies, and thyroid ultrasound results of the two groups of women of childbearing age were recorded. Urinary BPA and urinary BPA/creatinine were detected. The difference of BPA levels between the two groups was compared. logistic regression was used to analyze the correlation between BPA and AITD.ResultsThe proportion of multiparous and serum thyroid stimulating hormone levels were significantly higher in the AITD group compared to the euthyroid group. Logistic regression analysis revealed that BPA levels did not exhibit a statistically significant association with AITD. Spearman correlation analysis revealed a statistically significant correlation between BPA and urinary iodine levels (r=0.30, P < 0.05), as well as a correlation between urinary BPA and free tetraiodothyronine (FT4) levels (r=0.29, P < 0.05).ConclusionThis study revealed a correlation between urinary BPA levels and FT4 levels. However, it did not establish a relationship between BPA and AITD in women of childbearing age.

ObjectiveInsufficient thyroid hormone levels during pregnancy, especially in the first trimester, adversely affect maternal and fetal health. However, the impact of isolated hypothyroxinemia (IH) on adverse pregnancy outcomes remains controversial. Therefore, this study aimed to investigate the association between IH during the first trimester and adverse pregnancy outcomes.MethodsThis prospective cohort study included 1236 pregnant women. Thyroid-stimulating hormone and free thyroxine levels were measured before 13 weeks of gestation. Logistic regression analysis and the Cochran-Armitage trend test were used to assess the association between IH in the first trimester and adverse pregnancy outcomes.ResultsIH during the first trimester was associated with an increased risk of macrosomia. After adjusting for confounding factors, including age, body mass index, parity, abnormal pregnancy history, fasting blood glucose, and total cholesterol, multivariate logistic regression analysis showed that IH in the first trimester remained an independent risk factor for macrosomia. In addition, the risk of macrosomia increased with IH severity. However, no significant relationship was found between IH during the first trimester and gestational diabetes mellitus, hypertensive disorders of pregnancy, spontaneous abortion, premature rupture of membranes, placental abruption, oligohydramnios, premature delivery, fetal distress, or low birth weight.ConclusionIH during the first trimester did not increase the risk of adverse pregnancy outcomes, except for macrosomia.

BackgroundTo explore the association between thyroid hormones and gestational diabetes mellitus in euthyroid pregnant women, with the aim of preventing the occurrence of gestational diabetes mellitus.MethodsIn this prospective study, a total of 1222 euthyroid pregnant women in their first trimester were recruited at Peking University International Hospital between December 2017 and March 2019. These participants underwent an oral glucose tolerance test during the 24-28 weeks of gestation.ResultsDuring early pregnancy, the gestational diabetes mellitus group displayed lower levels of free thyroxine when compared to the non-gestational diabetes mellitus group. Additionally, the ratio of free triiodothyronine to free thyroxine in the gestational diabetes mellitus group during early pregnancy was significantly higher (p

Abstract Background Cancer predisposition is most often studied in the context of single cancers. However, inherited cancer predispositions can also give rise to multiple primary cancers. Yet, there is a paucity of studies on genetic predisposition in multiple primary cancers, especially those outside of well-defined cancer predisposition syndromes. This study aimed to identify germline variants associated with dual primary cancers of the breast and lung. Methods Exome sequencing was performed on germline DNA from 55 Singapore patients (52 [95%] never-smokers) with dual primaries in the breast and lung, confirmed by histopathology. Using two large control cohorts: the local SG10K_Health (n = 9770) and gnomAD non-cancer East Asians (n = 9626); and two additional local case cohorts of early-onset or familial breast cancer (n = 290), and lung cancer (n = 209), variants were assessed for pathogenicity in accordance with ACMG/AMP guidelines. In particular, comparisons were made with known pathogenic or likely pathogenic variants in the ClinVar database, pathogenicity predictions were obtained from in silico prediction software, and case–control association analyses were performed. Results Altogether, we identified 19 pathogenic or likely pathogenic variants from 16 genes, detected in 17 of 55 (31%) patients. Six of the 19 variants were identified using ClinVar, while 13 variants were classified pathogenic or likely pathogenic using ACMG/AMP guidelines. The 16 genes include well-known cancer predisposition genes such as BRCA2, TP53, and RAD51D; but also lesser known cancer genes EXT2, WWOX, GATA2, and GPC3. Most of these genes are involved in DNA damage repair, reaffirming the role of impaired DNA repair mechanisms in the development of multiple malignancies. These variants warrant further investigations in additional populations. Conclusions We have identified both known and novel variants significantly enriched in patients with primary breast and lung malignancies, expanding the body of known cancer predisposition variants for both breast and lung cancer. These variants are mostly from genes involved in DNA repair, affirming the role of impaired DNA repair in the predisposition and development of multiple cancers.

Abstract Background Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the pro-inflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL-6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels. Methods The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by gender, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously. Result The results showed that patients with TRS had higher serum IL-6 levels than patients with PRS (p = 0.002). In females, IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005). And a positive correlation tendency was observed between IL-6 levels and PANSS general sub-scores (r = 0.31, p = 0.039), although this correlation was not significant after correcting for multiple comparisons. Whereas, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124) in males. Conclusion Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.

Abstract Background For the majority of individuals with early-onset or familial breast cancer referred for genetic testing, the genetic basis of their familial breast cancer remains unexplained. To identify novel germline variants associated with breast cancer predisposition, whole-exome sequencing (WES) was performed. Methods WES on 290 BRCA1/BRCA2-negative Singaporeans with early-onset breast cancer and/or a family history of breast cancer was done. Case–control analysis against the East-Asian subpopulation (EAS) from the Genome Aggregation Database (gnomAD) identified variants enriched in cases, which were further selected by occurrence in cancer gene databases. Variants were further evaluated in repeated case–control analyses using a second case cohort from the database of Genotypes and Phenotypes (dbGaP) comprising 466 early-onset breast cancer patients from the United States, and a Singapore SG10K_Health control cohort. Results Forty-nine breast cancer-associated germline pathogenic variants in 37 genes were identified in Singapore cases versus gnomAD (EAS). Compared against SG10K_Health controls, 13 of 49 variants remain significantly enriched (False Discovery Rate (FDR)-adjusted p

Nitrous oxide (N2O) is an industrial waste gas (e.g., from the production of adipic acid), which damages the ozone layer and causes the greenhouse effect. Density functional theory calculations were employed to investigate the mechanism of direct catalytic decomposition of N2O and selective catalytic reduction (SCR) of N2O by CO over Fe-ZSM-5 zeolites. Two stable Fe-active sites with six-membered ring structures on Fe-ZSM-5 were considered. The calculations indicate that the decomposition of N2O is affected by the coordination environment around Fe and can occur through two reaction pathways. However, there is invariably a more considerable energy hurdle for the initiation of the second stage of N2O decomposition. When CO participated in the reaction, it showed good reactivity and stability, the reaction energy barriers of the rate-limiting step were reduced by roughly 20.57 kcal/mol compared to the direct catalytic decomposition of N2O. CO exhibited a superior electron-donating ability and orbital hybridization performance during the reaction, which enhanced the cyclicity of the N2O reduction catalytic process. Our calculations confirmed the significant role of CO in N2O reduction over Fe-ZSM-5 observed in previous studies. This study provides a valuable theoretical reference for exploring CO-SCR methods for N2O reduction over Fe-based zeolite catalysts.

In this study, the ultrasound-assisted extraction (UAE) conditions of flavonoids from Lactuca indica L.cv. Mengzao (LIM) leaves was optimized, and the flavonoids content and their antioxidant potential in different parts were analyzed. The optimal extraction parameters to obtain the highest total flavonoids content (TFC) were a a ratio of liquid to solid of 24.76 mL/g, ultrasonic power of 411.43 W, ethanol concentration of 58.86% and an extraction time of 30 min, the average TFC of LIM leaves could reach 48.01 mg/g. For the yield of flavonoids, the UAE method had the best extraction capacity compared with solvent extraction and microwave-assisted extraction (MAE). In general, the TFC in different parts of LIM followed the order flower > leaf > stem > root, the flowering period is the most suitable harvesting period. From ultra-high performance liquid chromatography-mass spectrometry (UPLC–MS) quantification, the flower samples showed significantly higher six flavonoids and had the highest radical scavenging capacities compared to other samples. A high positive correlation was observed between the antioxidant activity and TFC, luteolin-7-O-glucoside and rutin were significantly (p < 0.05) correlated with all antioxidant evaluations. This study provides valuable information for the development and utilization of flavonoids in Lactuca indica as ingredients in food, feed and nutritional health products.