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BackgroundIt remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM.Methods and findingsThis open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection.ConclusionsThe combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity.Trial registrationClinicalTrials.gov Identifier: NCT03493048.

As an important gas signaling molecule, hydrogen sulfide (H2S) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary, reproductive systems. In particular, H2S not only regulates female reproductive function but also holds great promise in the treatment of male reproductive diseases and disorders, such as erectile dysfunction, prostate cancer, varicocele, and infertility. In this review, we summarize the relationship between H2S and male reproductive organs, including the penis, testis, prostate, vas deferens, and epididymis. As lower urinary tract symptoms have a significant impact on penile erection disorders, we also address the potential ameliorative effects of H2S in erectile dysfunction resulting from bladder disease. Additionally, we discuss the regulatory role of H2S in cavernous smooth muscle relaxation, which involves the NO/cGMP pathway, the RhoA/Rho-kinase pathway, and K+ channel activation. Recently, various compounds that can alleviate erectile dysfunction have been reported to be at least partly dependent on H2S. Therefore, understanding the role of H2S in the male reproductive system may help develop novel strategies for the clinical treatment of male reproductive system diseases.

Methods: Our approach encompasses analyzing MAP7's expression levels across various datasets and clinical specimens, evaluating its association with patient outcomes, and probing its influence on ovarian cancer cell dynamics such as proliferation, migration, invasion, and apoptosis. Results: We have identified significant upregulation of MAP7 in ovarian cancer tissues, which correlates with advanced disease stages, higher pathological grades, and unfavorable prognoses. Functionally, the inhibition of MAP7 suppresses cancer cell proliferation, migration, and invasion while promoting apoptosis. Notably, the silencing of MAP7 attenuates the epithelial-mesenchymal transition (EMT) and disrupts Wnt/β-catenin pathway signaling—two critical processes implicated in metastasis and chemoresistance. In cisplatin-resistant A2780-DDP cells, the downregulation of MAP7 effectively reverses their resistance to cisplatin. Furthermore, the nuclear localization of MAP7 in these cells underscores its pivotal role in driving cisplatin resistance by modulating the transcriptional regulation and interaction dynamics of β-catenin. Conclusion: Our findings position MAP7 as a pivotal element in ovarian cancer advancement and cisplatin resistance, primarily through its modulation of EMT and the Wnt/β-catenin pathway. Its association with poor clinical outcomes underscores its potential as both a prognostic marker and a therapeutic target. Strategies aimed at MAP7 could represent a new frontier in combating chemotherapy resistance in ovarian cancer, emphasizing its significance in crafting complementary treatments for this disease.

IntroductionThe branched-chain amino acids (BCAAs) are essential to mammalian growth and development but aberrantly elevated in obesity and diabetes. Each BCAA has an independent and specific physio-biochemical effect on the host. However, the exact molecular mechanism of the detrimental effect of valine on metabolic health remains largely unknown.Methods and resultsThis study showed that for lean mice treated with valine, the hepatic lipid metabolism and adipogenesis were enhanced, and the villus height and crypt depth of the ileum were significantly increased. Transcriptome profiling on white and brown adipose tissues revealed that valine disturbed multiple signaling pathways (e.g., inflammation and fatty acid metabolism). Integrative cecal metagenome and metabolome analyses found that abundances of Bacteroidetes decreased, but Proteobacteria and Helicobacter increased, respectively; and 87 differential metabolites were enriched in several molecular pathways (e.g., inflammation and lipid and bile acid metabolism). Furthermore, abundances of two metabolites (stercobilin and 3-IAA), proteins (AMPK/pAMPK and SCD1), and inflammation and adipogenesis-related genes were validated.DiscussionValine treatment affects the intestinal microbiota and metabolite compositions, induces gut inflammation, and aggravates hepatic lipid deposition and adipogenesis. Our findings provide novel insights into and resources for further exploring the molecular mechanism and biological function of valine on lipid metabolism.

Selinexor, a selective inhibitor of nuclear export (SINE), is gaining recognition beyond oncology for its potential in anti-inflammatory therapy. This review elucidates Selinexor’s dual action, highlighting its anti-tumor efficacy in various cancers including hematologic malignancies and solid tumors, and its promising anti-inflammatory effects. In cancer treatment, Selinexor has demonstrated benefits as monotherapy and in combination with other therapeutics, particularly in drug-resistant cases. Its role in enhancing the effectiveness of bone marrow transplants has also been noted. Importantly, the drug’s impact on key inflammatory pathways provides a new avenue for the management of conditions like sepsis, viral infections including COVID-19, and chronic inflammatory diseases such as Duchenne Muscular Dystrophy and Parkinson’s Disease. The review emphasizes the criticality of managing Selinexor’s side effects through diligent dose optimization and patient monitoring. Given the complexities of its broader applications, extensive research is called upon to validate Selinexor’s long-term safety and effectiveness, with a keen focus on its integration into clinical practice for a diverse spectrum of disorders.

Objective To evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors.Methods In this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid tumors were enrolled. The study consisted of two distinct phases: (1) the dose escalation phase and (2) the dose expansion phase; with three dose groups in the dose escalation phase based on dose levels (5.0×109 viral particles (VP)/subject, 5.0×1010 VP/subject, and 5.0×1011 VP/subject). Subjects were administered YSCH-01 injection via intratumoral injections. The safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0, and the efficacy evaluation was performed using Response Evaluation Criteria in Solid Tumor V.1.1.Results 14 subjects were enrolled in the study, including 9 subjects in the dose escalation phase and 5 subjects in the dose expansion phase. Of the 13 subjects included in the full analysis set, 4 (30.8%) were men and 9 (69.2%) were women. The most common tumor type was lung cancer (38.5%, 5 subjects), followed by breast cancer (23.1%, 3 subjects) and melanoma (23.1%, 3 subjects). During the dose escalation phase, no subject experienced dose-limiting toxicities. The content of recombinant L-IFN adenovirus genome and recombinant L-IFN protein in blood showed no trend of significant intergroup changes. No significant change was observed in interleukin-6 and interferon-gamma. For 11 subjects evaluated for efficacy, the overall response rate with its 95% CI was 27.3% (6.02% to 60.97%) and the disease control rate with its 95% CI was 81.8% (48.22% to 97.72%). The median progression-free survival was 4.97 months, and the median overall survival was 8.62 months. In addition, a tendency of decrease in the sum of the diameters of target lesions was observed. For 13 subjects evaluated for safety, the overall incidence of adverse events (AEs) was 92.3%, the overall incidence of adverse drug reactions (ADRs) was 84.6%, and the overall incidence of >Grade 3 AEs was 7.7%, while no AEs/ADRs leading to death occurred. The most common AEs were fever (69.2%), nausea (30.8%), vomiting (30.8%), and hypophagia (23.1%).Conclusions The study shows that YSCH-01 injections were safe and well tolerated and exhibited preliminary efficacy in patients with advanced solid tumors, supporting further investigation to evaluate its efficacy and safety.Trial registration number NCT05180851.

BackgroundAccumulating evidence suggests that the autism spectrum disorder (ASD) population exhibits altered hormone levels, including androgens. However, studies on the regulation of androgens, such as testosterone and dehydroepiandrosterone (DHEA), in relation to sex differences in individuals with ASD are limited and inconsistent. We conducted the systematic review with meta-analysis to quantitatively summarise the blood, urine, or saliva androgen data between individuals with ASD and controls.MethodsA systematic search was conducted for eligible studies published before 16 January 2023 in six international and two Chinese databases. We computed summary statistics with a random-effects model. Publication bias was assessed using funnel plots and heterogeneity using I2 statistics. Subgroup analysis was performed by age, sex, sample source, and measurement method to explain the heterogeneity.Results17 case-control studies (individuals with ASD, 825; controls, 669) were assessed. Androgen levels were significantly higher in individuals with ASD than that in controls (SMD: 0.27, 95% CI: 0.06–0.48, P=0.01). Subgroup analysis showed significantly elevated levels of urinary total testosterone, urinary DHEA, and free testosterone in individuals with ASD. DHEA level was also significantly elevated in males with ASD.ConclusionAndrogen levels, especially free testosterone, may be elevated in individuals with ASD and DHEA levels may be specifically elevated in males.

Background Pelvic pain is a common complaint of discomfort in women, with an increasing incidence and seriously affecting patients’ quality of life. Its etiology involves multiple systems and disciplines, and therefore treatment modalities are diverse. Transcutaneous electrical acupoint stimulation (TEAS) therapy is a classic analgesic means, and electrical stimulation of local acupoints can achieve obvious analgesic effects. This review aims to discuss the application of TEAS for the treatment of various types of pelvic pain, the selection of optimal parameters and the renewal of equipment.Method Result TEAS for treatment of pelvic pain in women has been reported mainly for endometriosis, pelvic inflammatory disease (PID), intrauterine adhesion (IUA), pelvic stasis syndrome, interstitial cystitis, primary dysmenorrhoea and other diseases. And for parameter selection, the most used of frequency is dilatational wave, the most used stimulation intensity is 10–20 mA, and the acupoint selection should be based on the specific conditions of the patient.Conclusions The analgesic mechanism of TEAS has not been fully elucidated, but the efficacy of the treatment is remarkable and there are no significant adverse effects. The selection of the parameters for TEAS and the combination of acupoints for different pains are still the main directions of future research.

Background: The adverse effects of pulmonary arterial hypertension (PAH) on physical, emotional, and health-related quality of life (HRQoL) remain primarily unrecognized, especially in resource-limited settings. Objectives: This study aims to characterize the HRQoL of patients with PAH in this area and also identify the potential role of clinically relevant characteristics, including the 6-min walk distance test (6MWD), WHO-Functional Classification (WHO-FC), and mental health in the occurrence of lowering quality of life. Design: This was a cross-sectional observational study. Methods: Inpatients with PAH were chosen from a tertiary hospital located in Gansu province, China. All participants were interviewed face-by-face by using questionnaires, including items from the 36-Item Short Form Health Survey (SF-36), the self-rating anxiety scale, and the self-rating depression scale. Data on demographic and clinically relevant characteristics, including WHO-FC and 6MWD, were also collected by tracing medical recorders. Multiple linear regression analysis was used to determine the association between demographic, clinically relevant characteristics data, and physical component summary (PCS) or mental component summary (MCS) in SF-36. Results: Of the 152 participants, SF-36 differed significantly from Chinese norms in all eight domains, with role-physical (21.55 ± 9.87) less than one-third of the norm (88.79 ± 28.49). Multiple linear regression results showed that the factors with the greatest impact on PCS were anxiety scores (β = −0.22, p = 0.001), followed by WHO-FC (β = −0.16, p = 0.014) and 6MWD (β = 0.15, p = 0.036). The factors with the greatest impact on MCS were WHO-FC (β = −0.30, p

IntroductionWith improvements in living conditions, modern individuals exhibit a pronounced inclination towards a high-fat diet, largely because of its distinctive gustatory appeal. However, the association between high-fat diets and metabolic complications has largely been ignored, and metabolic diseases such as obesity and non-alcoholic fatty liver disease now constitute a major public health concern. Because high-fat diets increase the risk of metabolic diseases, a thorough investigation into the impact of high-fat diets on gut microbiota and metabolism is required.MethodsWe utilize 16S rRNA sequencing and untargeted metabolomics analysis to demonstrate that SD rats fed a high-fat diet exhibited marked alterations in gut microbiota and plasma, intestinal metabolism.ResultsChanges in gut microbiota included a decreased abundance at phylum level for Verrucomicrobiota, and a decreased abundance at genus level for Akkermansia, Ralstonia, Bacteroides, and Faecalibacterium. Additionally, significant changes were observed in both intestinal and plasma metabolite levels, including an upregulation of bile acid metabolism, an upregulation of glucose-lipid metabolism, and increased levels of metabolites such as norlithocholic acid, cholic acid, D-fructose, D-mannose, fructose lactate, and glycerophosphocholine. We also investigated the correlations between microbial communities and metabolites, revealing a significant negative correlation between Akkermansia bacteria and cholic acid.DiscussionOverall, our findings shed light on the relationship between symbiotic bacteria associated with high-fat diets and metabolic biomarkers, and they provide insights for identifying novel therapeutic approaches to mitigate disease risks associated with a high-fat diet.

In this article, we study the evolution of the two-qubit system with Ising spin-chain environment by choosing the Lindblad equation to describe this process. First, we expand the Hamiltonian of a two-qubit system with its eigenstates and give the Lindblad equation for the evolution of the two-qubit system with Ising spin-chain as the environment. Compared with directly calculating the differential equation between elements of density matrix, we choose a method to solve the Lindblad equation with a smaller calculation dimension. Finally, by constructing an operator solution with operators, we obtain the dynamics of the two-qubit system with Ising spin-chain environment.

During the sinking process of ultra-large onshore caisson, the structural stress of caisson will change significantly due to the changes of earth pressure, end resistance, water level in caisson and attitude of caisson. Based on the south anchoring onshore caisson project of Nanjing Longtan Yangtze River Bridge, the structural stress analyses were carried out based on the automated caisson monitoring data. The results show that the automated monitoring system can acquire the key data of caisson in real time and efficiently, and the monitoring results reflect the structural stress and displacement characteristics in different construction stages. The vertical earth pressure at the bottom four corners of the caisson is significantly greater than the other positions, indicating that there is an obvious stress concentration phenomenon at the four corners. The stress at the bottom of the horizontal earth pressure monitoring is smaller than that at the middle and bottom of caisson, which verifies the existence of stress disturbance area around the cutting. Steel shell concrete at the bottom of partition wall is the weakest position of caisson structure, and the structural safety risk is higher from the first casting to the second sinking. If the risk of tensile cracking occurs in the process of casting, each diagonal can be carried out several times to make full use of the structure's own resistance to reduce the development of tensile stress. The conclusion can be used for reference in the design and construction of similar projects.

Needle-type sensor, characterized by its slender, elongated shape, is a promising sensing method due to its rapid response, high sensitivity, and portability. Recently, the needle-type sensor technology has garnered increasing attention, leading to its accelerated development and extensive use in medical and healthcare, environmental monitoring, and geosciences. However, there remains a need for a comprehensive review of existing research. Here, we utilize scientometric analysis, which is booming recently, to conduct a comprehensive investigation of the needle-type sensor field. This analysis covers various aspects, including annual trends, journals, institutions, countries, disciplines, authors, references, and keywords of 136,667 publications from the Web of Science Core Collection (WoSCC) database spanning from January 1, 2004, to January 1, 2024. Additionally, we identify current hotspots, frontiers, and predict future trends. Eventually, three research hotspots are refined: multidisciplinary materials science, sensor miniaturization and integration, and biomedical engineering, indicating that further investigations may focus on creating biocompatible materials to enhance sensing properties, optimizing sensor structure through miniaturization and integration methods, and improving clinical applications in biomedical engineering. This work may facilitate the development of needle-type sensors.

Summary: Iron overload is closely associated with metabolic dysfunction. However, the role of iron in the hypothalamus remains unclear. Here, we find that hypothalamic iron levels are increased, particularly in agouti-related peptide (AgRP)-expressing neurons in high-fat-diet-fed mice. Using pharmacological or genetic approaches, we reduce iron overload in AgRP neurons by central deferoxamine administration or transferrin receptor 1 (Tfrc) deletion, ameliorating diet-induced obesity and related metabolic dysfunction. Conversely, Tfrc-mediated iron overload in AgRP neurons leads to overeating and adiposity. Mechanistically, the reduction of iron overload in AgRP neurons inhibits AgRP neuron activity; improves insulin and leptin sensitivity; and inhibits iron-induced oxidative stress, endoplasmic reticulum stress, nuclear factor κB signaling, and suppression of cytokine signaling 3 expression. These results highlight the critical role of hypothalamic iron in obesity development and suggest targets for treating obesity and related metabolic disorders.

The skin color of koi carp (Cyprinus carpio L.) is one of the traits that most influence their ornamental and economic values. The present study suggested the effects of temperature fluctuation on koi carp in terms of skin color and plasma carotenoids and related-metabolites. The main results were as follows. (1) The vulnerability of koi skin color to acute temperature stress was in the order of white koi> black koi> yellow koi. Both high- (25°C-30°C-25°C) and low-temperature (25°C-20°C-25°C) fluctuations tended to decrease the saturation of white koi. The temperature fluctuation had little effects on the skin color of black and yellow koi. (2) Targeted metabolomics analysis indicated that the effects of cooling stress on oxycarotenoids of all five koi varieties were reversible. The plasma oxycarotenoids in mirror koi with all colors were insensitive to acute heat stress. However, the cooling process from a high temperature (30°C-25°C) still made contributions to the increase of oxycarotenoids. (3) The principal component analysis confirmed the deviation of carotenoid-related metabolites after high temperature fluctuation and the reversibility after low temperature fluctuation. Finally, the correlation analysis revealed that koi skin brightness was negatively correlated with the plasma guanine content and that temperature fluctuations might change koi skin brightness via the L(-)-epinephrine-guanine pathway. The red hue and yellow hue were negatively correlated with the oxycarotenoids in plasma, suggesting that oxycarotenoids were favorable for enhancing koi skin color saturation. Overall, this study revealed the direct action of temperature fluctuations on the skin color and carotenoid-related metabolites of koi.

BackgroundHyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear.MethodsA secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups.ResultsA total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching (P

GaN power electronic devices, such as the lateral AlGaN/GaN Schottky barrier diode (SBD), have received significant attention in recent years. Many studies have focused on optimizing the breakdown voltage (BV) of the device, with a particular emphasis on achieving ultra-high-voltage (UHV, > 10 kV) applications. However, another important question arises: can the device maintain a BV of 10 kV while having a low turn-on voltage (Von)? In this study, the fabrication of UHV AlGaN/GaN SBDs was demonstrated on sapphire with a BV exceeding 10 kV. Moreover, by utilizing a double-barrier anode (DBA) structure consisting of platinum (Pt) and tantalum (Ta), a remarkably low Von of 0.36 V was achieved. This achievement highlights the great potential of these devices for UHV applications.

Folate receptor autoantibody (FRAA) has caught increasing attention since its discovery in biological fluids of patients with autism spectrum disorder (ASD), but quantification and understanding of its function are still in their infancy. In this study, we aimed to quantify serum binding-FRAA and explore its relation with serum folate, vitamin B12 (VB12) and ferritin. We quantitated serum binding-FRAA in 132 ASD children and 132 typically-developing (TD) children, as well as serum levels of folate, VB12 and ferritin. The results showed that serum binding-FRAA in the ASD group was significantly lower than that in the TD group (p 0.05). However, there was significant difference in boys between these two groups, not girls. Additionally, the combination of nitrite and binding-FRAA showed potential diagnostic value in patients with ASD (AUC > 0.7). Moreover, in the ASD group, the level of folate was consistent with that of binding-FRAA, whereas in the TD group, the binding-FRAA level was high when the folate level was low. Altogether, these differences revealed that the low serum FRAA in autistic children was mediated by multiple factors, which deserves more comprehensive investigation with larger population and mechanistic studies.

Abstract Background Several studies have indicated that magnetic resonance imaging radiomics can predict survival in patients with breast cancer, but the potential biological underpinning remains indistinct. Herein, we aim to develop an interpretable deep-learning-based network for classifying recurrence risk and revealing the potential biological mechanisms. Methods In this multicenter study, 1113 nonmetastatic invasive breast cancer patients were included, and were divided into the training cohort (n = 698), the validation cohort (n = 171), and the testing cohort (n = 244). The Radiomic DeepSurv Net (RDeepNet) model was constructed using the Cox proportional hazards deep neural network DeepSurv for predicting individual recurrence risk. RNA-sequencing was performed to explore the association between radiomics and tumor microenvironment. Correlation and variance analyses were conducted to examine changes of radiomics among patients with different therapeutic responses and after neoadjuvant chemotherapy. The association and quantitative relation of radiomics and epigenetic molecular characteristics were further analyzed to reveal the mechanisms of radiomics. Results The RDeepNet model showed a significant association with recurrence-free survival (RFS) (HR 0.03, 95% CI 0.02–0.06, P

Abstract Background Glioblastoma (GBM), the most common primary malignant brain tumor, has a poor prognosis, with a median survival of only 14.6 months. The Warburg effect is an abnormal energy metabolism, which is the main cause of the acidic tumor microenvironment. This study explored the role of the Warburg effect in the prognosis and immune microenvironment of GBM. Methods A prognostic risk score model of Warburg effect‐related genes (Warburg effect signature) was constructed using GBM cohort data from The Cancer Genome Atlas. Cox analysis was performed to identify independent prognostic factors. Next, the nomogram was built to predict the prognosis for GBM patients. Finally, the drug sensitivity analysis was utilized to find the drugs that specifically target Warburg effect‐related genes. Results Age, radiotherapy, chemotherapy, and WRGs score were confirmed as independent prognostic factors for GBM by Cox analyses. The C‐index (0.633 for the training set and 0.696 for the validation set) and area under curve (>0.7) indicated that the nomogram exhibited excellent performance. The calibration curve also indicates excellent consistency of the nomogram between predictions and actual observations. In addition, immune microenvironment analysis revealed that patients with high WRGs scores had high immunosuppressive scores, a high abundance of immunosuppressive cells, and a low response to immunotherapy. The Cell Counting Kit‐8 assays showed that the drugs targeting Warburg effect‐related genes could inhibit the GBM cells growth in vitro. Conclusion Our research showed that the Warburg effect is connected with the prognosis and immune microenvironment of GBM. Therefore, targeting Warburg effect‐related genes may provide novel therapeutic options.

Background: Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been demonstrated to be effective in treating patients with virus-induced acute respiratory distress syndrome (ARDS). However, whether the management of ECMO is different in treating H1N1 influenza and coronavirus disease 2019 (COVID-19)-associated ARDS patients remains unknown. Methods: This is a retrospective cohort study. We included 12 VV-ECMO-supported COVID-19 patients admitted to The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Eighth People's Hospital, and Wuhan Union Hospital West Campus between January 23 and March 31, 2020. We retrospectively included VV-ECMO-supported patients with COVID-19 and H1N1 influenza-associated ARDS. Clinical characteristics, respiratory mechanics including plateau pressure, driving pressure, mechanical power, ventilatory ratio (VR) and lung compliance, and outcomes were compared. Results: Data from 25 patients with COVID-19 (n=12) and H1N1 (n=13) associated ARDS who had received ECMO support were analyzed. COVID-19 patients were older than H1N1 influenza patients (P=0.004). The partial pressure of arterial carbon dioxide (PaCO2) and VR before ECMO initiation were significantly higher in COVID-19 patients than in H1N1 influenza patients (P

Abstract Background There is limited longitudinal evidence on the hypertensive effects of long-term exposure to ambient O3. We investigated the association between long-term O3 exposure at workplace and incident hypertension, diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), and mean arterial pressure (MAP) in general working adults. Methods We conducted a cohort study by recruiting over 30,000 medical examination attendees through multistage stratified cluster sampling. Participants completed a standard questionnaire and comprehensive medical examination. Three-year ambient O3 concentrations at each employed participant’s workplace were estimated using a two-stage machine learning model. Mixed-effects Cox proportional hazards models and linear mixed-effects models were used to examine the effect of O3 concentrations on incident hypertension and blood pressure parameters, respectively. Generalized additive mixed models were used to explore non-linear concentration-response relationships. Results A total of 16,630 hypertension-free working participants at baseline finished the follow-up. The mean (SD) O3 exposure was 45.26 (2.70) ppb. The cumulative incidence of hypertension was 7.11 (95% CI: 6.76, 7.47) per 100 person-years. Long-term O3 exposure was independently, positively and non-linearly associated with incident hypertension (Hazard ratios (95% CI) for Q2, Q3, and Q4 were 1.77 (1.34, 2.36), 2.06 (1.42, 3.00) and 3.43 (2.46, 4.79), respectively, as compared with the first quartile (Q1)), DBP (β (95% CI) was 0.65 (0.01, 1.30) for Q2, as compared to Q1), SBP (β (95% CI) was 2.88 (2.00, 3.77), 2.49 (1.36, 3.61) and 2.61 (1.64, 3.58) for Q2, Q3, and Q4, respectively), PP (β (95% CI) was 2.12 (1.36, 2.87), 2.03 (1.18, 2.87) and 2.14 (1.38, 2.90) for Q2, Q3, and Q4, respectively), and MAP (β (95% CI) was 1.39 (0.76, 2.02), 1.04 (0.24, 1.84) and 1.12 (0.43, 1.82) for Q2, Q3, and Q4, respectively). The associations were robust across sex, age, BMI, and when considering PM2.5 and NO2. Conclusions To our knowledge, this is the first cohort study in the general population that demonstrates the non-linear hypertensive effects of long-term O3 exposure. The findings are particularly relevant for policymakers and researchers involved in ambient pollution and public health, supporting the integration of reduction of ambient O3 into public health interventions.

Abstract Tephritidae pests are significant agricultural pests with a notable impact on the economy, with a wide range of species and most having broad host ranges and strong reproductive abilities. However, the wolfberry fruit fly, Neoceratitis asiatica (Becker), is a Tephritidae fly which only harms wolfberry. Here, we assembled and annotated N. asiatica genome at the chromosome level and compared it with the genomic and transcriptomic information from other Tephritidae flies. The assembled genome of N. asiatica had a size of 563.8 Mb and achieved a completeness level of 99.1%, 18,387 genes were annotated totally. All contigs were assembled into 7 linkage groups with an N50 of 93.166 Mb assisted by the Hi-C technique. The high-quality genome developed here will provide a significant resource for exploring the genetic basis of the adaptive and reproductive differences among various Tephritidae pests, and provides an important theoretical basis for the prevention and control of Tephritidae pests.

Abstract The winter upper troposphere/lower stratosphere temperature/vertical motion response over the extratropical North Pacific induced by North Atlantic changes is not well understood. Here, using robust diagnostic calculations conducted in a fully coupled high-resolution climate model, we correct the North Atlantic ocean circulation biases and show that during wintertime, the North Atlantic cold surface temperature biases lead to a warmer upper troposphere/lower stratosphere over the extratropical North Pacific. In the upper troposphere/lower stratosphere over the extratropical North Pacific, this winter warming temperature response is linked to the vertical motion response through a simple leading order thermodynamic relationship between changes in the horizontal advection and adiabatic heating. The upper troposphere/lower stratosphere vertical motion response, which is also associated with the North Atlantic induced Walker circulation response over the tropical North Pacific, can provide a rough estimation of the upper troposphere/lower stratosphere warming response over the extratropical North Pacific.

Abstract Background Despite the proven effectiveness of simulation-based learning activities, its adoption in medical education remains limited, and the influence of simulation on student motivation, particularly subjective task values, is seldom explored. This study aimed to investigate the impact of a simulation-based learning activity on student learning and subjective task values in a medical morphology-related course of Human Parasitology. Methods A quasi-experimental study was conducted with 113 Chinese undergraduate medical students who participated in a Human Parasitology course during April to May 2022. Students were divided into two groups: Simulation Group (n = 55), where students used the simulation, and Lecture Group (n = 58), where students attended an online lecture. Students’ learning was measured prior to the intervention, immediately after the intervention, and three weeks later to assess knowledge retention. The subjective task values questionnaire was administered before and after the interventions. Data were analyzed using one-way ANCOVA and MANOVA. Results Students in the Simulation Group exhibited significantly higher knowledge gain compared to the Lecture Group [F (1,110) = 23.69, p

Tomato (Solanum lycopersicum L. cv. Zhongza NO. 9) was used as the experimental material to investigate the effects of nocturnal LED supplemental light with the photosynthetic photon flux density (PPFD) of 100, 200, 300 μmol·m−2·s−1, and the light time of 1, 2 h on the seedling quality in a controlled environment, with seedlings without nocturnal supplemental lighting serving as the control. The results demonstrate that an increase in PPFD at night progressively enhances the plant height and leaf number of tomato seedlings, while stem diameter and leaf area initially increase and subsequently decrease. Although light time and light period-of-time at night did not significantly affect seedling morphology, PPFD and light time notably influenced chlorophyll content and net photosynthetic rate. An optimal lighting energy amount at night augmented photosynthetic capacity. However, excessive PPFD induced photoinhibition in the leaves. Additionally, appropriate nocturnal LED supplemental lighting significantly improved the antioxidant capacity of the seedlings, increased proline content, reduced malondialdehyde content, and bolstered the self-protection mechanisms of the seedlings against nocturnal light stress. Both the PPFD and light time at night promoted biomass accumulation in tomato seedlings. Specifically, when supplemental lighting was applied for 2 h at an intensity of 200 μmol·m−2·s−1, both the fresh and dry weights of the shoot and root significantly increased, and the seedling health index was highest. Therefore, appropriate nocturnal LED supplemental lighting positively impacts the health index and photosynthate accumulation of tomato seedlings, but controlling PPFD is essential to avoid photoinhibition.

This meta-synthesis crosses international borders by analyzing successful principalship across nine countries. With careful, detailed, systematic, and analytic synthesis, it critically explores research-informed understandings of successful principal leadership over the last 20 years. The paper is an interim report of reviews of the 85 articles and 23 chapters produced by the International Successful School Principal Project (ISSPP), the largest, longest-running international research project in this field. In that project, success is defined as the principal’s ability to grow and sustain students’ academic, personal, and social developments and achievements over time. The results add to existing knowledge of how successful school principals achieve success by examining high-quality, published case study evidence from Australia, Cyprus, Israel, New Zealand, Norway, Sweden, Spain, the UK, and the US. Results suggest common sets of core values, qualities, and practices among school principals, regardless of national contexts, conditions, or cultures. Because the research design is multi-perspective and multi-layered, the case studies also show significant, context-informed differences in timing, pace, and extent of application of improvement strategies. Thus, the findings of this synthesis paint a thorough and cohesive picture of who successful principals are and what they do over time at the global level to achieve success, as they navigate values-led school success in different contexts and improvement phases within complex internal and external ecological chrono-, macro-, exo-, meso-, and microsystems.

Arthropods play a crucial role in ecological processes and agricultural productivity. Soil physicochemical properties, indicators of soil health, are closely linked to arthropod communities. Gravel-sand mulching, commonly employed in arid farming, initially enhances water retention and temperature regulation but may contribute to land degradation with prolonged use. This study investigated how varying tillage durations affected soil properties and arthropod diversity under gravel-sand mulching. The analysis employed multiple comparison methods, covariance analysis (ANCOVA), non-metric multidimensional scaling (NMDS), and redundancy analysis (RDA). The results indicated that while soil fertility was better preserved in cultivated fields compared to in the desert grassland, arthropod diversity significantly decreased with longer cultivation periods. A total of 1099 arthropods from 79 species were sampled, by Barber trap. The highest diversity was observed in native grassland (NG), with 305 arthropods from 39 species, while tillage 21 years (GPS-21Y) exhibited the lowest diversity, with only 103 arthropods from 6 species. Dominant species included the carnivores Labidura japonica and Cataglyphis aenes. The analysis revealed low similarity in arthropod communities between GPS-21Y and other fields and high similarity in soil physicochemical properties between NG and the transition zone (STZ). RDA showed available potassium (APP) was negatively correlated with arthropod species diversity and concentration, total Nitrogen (TN) was positively correlated with arthropod species diversity but negatively correlated with species concentration, total phosphorus (TP) was negatively correlated with arthropod species diversity and concentration. This study provides insights into the relationship between maintaining soil fertility and supporting arthropod diversity in grassland agriculture. While soil fertility and arthropod diversity were correlated, continuous cropping practices negatively impacted arthropod diversity, offering valuable information for pest management and sustainable agricultural practices.

The coffee industry is developing rapidly in the world, and the use of coffee filtration nonwovens (CFNs) is becoming more and more extensive; however, there is a lack of standards and research for its production and trade, and the quality of related products on the market is uneven at present. Here, eight double-layer composite coffee filtration nonwovens (D-LCCFNs) were prepared by using 5 g/m2 and 10 g/m2 polypropylene (PP) melt-blown nonwovens (MNs), 20 g/m2 PP spunbonded nonwovens and 20 g/m2 viscose/ES fiber chemically bonded nonwovens, and the physical properties, morphology and the filtration effect of coffee and purified water for the prepared samples were tested. It was found that the surface density of the microfiber layer (MNs) in the D-LCCFNs was negatively correlated with the coffee filtration rate; when the microfiber layer in the D-LCCFNs was in direct contact with the coffee, the liquid started to drip later, and the filtration rate of the coffee was slower; the filtration rate of the samples with the viscose/ES chemically bonded nonwovens was very fast. However, the samples without viscose/ES fibers basically did not filter pure water much, but they could filter out the coffee liquid normally, and the samples’ hydrophilicity increased significantly after filtering coffee.

This study explored the effect of the coach–athlete relationship perceived by college athletes on athletic behaviour, examining the mediating effect of psychological needs. This study was conducted with 254 college athletes using questionnaires, and the research instruments included the Coach–Athlete Relationship Scale, the Psychological Needs Scale, and the Athletic Behaviour Scale. The results of the study were as follows: (1) the coach–athlete relationship perceived by student-athletes had a direct positive and significant effect on athletic behaviours (β = 0.268, p < 0.001, and direct effect = 0.0344); and (2) psychological needs had a significant mediating effect between the coach–athlete relationship and athletic behaviours (indirect effect = 0.2433), and the mediating effect percentage was 41.56%. The overall mediation effect value was 0.5854. The findings of the study emphasized that, by improving the coach–athlete relationship, it could help to improve the psychological needs of college athletes and, thus, promote their positive motor behaviours. In the coach–athlete relationship, the effect of closeness on the promotion of motor behaviour was particularly significant, in which special attention and emphasis should be given to the closeness between coaches and athletes in a practical implementation. Subsequently, coaches should focus their training on enhancing the coach–athlete relationship as a crucial part of training in order to perform well in competitions.

To achieve high-density tomato seedlings in a plant factory with artificial lighting, tomatoes (Solanum lycopersicum Mill. cv. “Zhongza NO.9”) were used as the experimental material. This study expected to analyze the effects of light intensity (150, 200, 250, and 300 μmol·m−2·s−1) and light time (12 and 14 h), as well as daily light integral (DLI, 10.80, 12.60, and 12.96 mol·m−2·d−1) and sowing density (50, 72, and 105 holes per tray), on seedling quality. The results indicated that biomass accumulation, seedling quality, and energy use efficiency of seedlings significantly improved with an increase in DLI. At a DLI of 12.96 mol·m−2·d−1, seedlings sown at a density of 72 holes per tray exhibited comparable growth characteristics and biomass accumulation to those sown at 50 holes per tray. However, under lower DLIs, seedlings at 50 holes per tray displayed superior growth morphology and seedling quality compared to those at 72 holes per tray. This indicates that increasing the DLI can partially mitigate the negative effects of higher sowing density on seedling quality. Light use efficiency (LUE) and energy use efficiency (EUE) were not significantly different between seedlings at 72 and 105 holes per tray but were higher than those at 50 holes per tray. Therefore, optimizing parameters such as DLI and sowing density can effectively enhance the seedling quality, spatial use efficiency, and light use efficiency in industrial seedling production. Based on the results of this study, a DLI of 12.96 mol·m−2·d−1 (achieved with a light intensity of 300 μmol·m−2·s−1 and a light time of 12 h) and sowing density of 72 holes per tray are recommended for cultivating high-quality tomato seedlings while reducing energy consumption.

Colletotrichum fructicola shows morphological and genetic differences in plus and minus strains. However, the mechanism of the differentiation between two types of strains is still largely unclear. Our early transcriptome analysis revealed that CfHMG expression differed in plus and minus strains. To define the functions of the CfHMG gene, we constructed gene deletion mutants by homologous recombination. We found that a CfHMG deletion mutant of the minus strain, CfHMG-M, could lead to a reduction in perithecium sizes and densities on media and sterile perithecium formation compared with the minus wild type (WT), whereas there was no effect for the plus mutant CfHMG-P. In co-cultures between CfHMG-P and minus WT, CfHMG-M and plus WT, or CfHMG-P and CfHMG-M, the quantities of perithecia were all reduced significantly. When conidial suspensions were inoculated on non-wounded apple fruit, it was found that the virulence of the minus mutant decreased significantly but not for the plus one. Further, we found that the virulence decrease in minus mutants was caused by a decrease in the conidium germination rate. Our results indicate that CfHMG of C. fructicola plays an important role in the mating line formation between the plus and minus strain for both strains and differentially regulates the perithecium size, density, fertilization, and virulence of the minus strain. The results are significant for further detecting the differentiated mechanisms between the plus and minus strains in Colletotrichum fungi.

Rooted in dynamic systems theory, convergent cross mapping (CCM) has attracted increased attention recently due to its capability in detecting linear and nonlinear causal coupling in both random and deterministic settings. One limitation with CCM is that it uses both past and future values to predict the current value, which is inconsistent with the widely accepted definition of causality, where it is assumed that the future values of one process cannot influence the past of another. To overcome this obstacle, in our previous research, we introduced the concept of causalized convergent cross mapping (cCCM), where future values are no longer used to predict the current value. In this paper, we focus on the implementation of cCCM in causality analysis. More specifically, we demonstrate the effectiveness of cCCM in identifying both linear and nonlinear causal coupling in various settings through a large number of examples, including Gaussian random variables with additive noise, sinusoidal waveforms, autoregressive models, stochastic processes with a dominant spectral component embedded in noise, deterministic chaotic maps, and systems with memory, as well as experimental fMRI data. In particular, we analyze the impact of shadow manifold construction on the performance of cCCM and provide detailed guidelines on how to configure the key parameters of cCCM in different applications. Overall, our analysis indicates that cCCM is a promising and easy-to-implement tool for causality analysis in a wide spectrum of applications.

In this study, we have developed an electrostatically suspended accelerometer (ESA) specifically designed for ground use. To ensure sufficient overload capacity and minimize noise resulting from high suspension voltage, we introduced a proof mass design featuring a hollow, thin-walled cylinder with a thin flange fixed at the center, offering the highest surface-area-to-mass ratio compared to various typical proof mass structures. Preload voltage is directly applied to the proof mass via a golden wire, effectively reducing the maximum supply voltage for suspension. The arrangement of suspension electrodes, offering five degrees of freedom and minimizing cross-talk, was designed to prioritize simplicity and maximize the utilization of electrode area for suspension purposes. The displacement detection and electrostatic suspension force were accurately modeled based on the structure. A controller incorporating an inverse winding mechanism was developed and simulated using Simulink. The simulation results unequivocally demonstrate the successful completion of the stable initial levitation process and suspension under ±1g overload.

Abstract Background To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge. Methods The clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of ΔZ value of weight at discharge

Abstract Aim To review the literature related to symptom management, clinical significance and related theoretical framework systems in adult patients with brain tumours. Background As understanding of symptoms or symptom clusters and underlying biologic mechanisms has grown, it is apparent that symptom science is moving forward. Although some progress has been made in the symptom science of solid tumours such as breast and lung neoplasms, insufficient attention has been paid to symptom management for patients suffering from brain tumours. Further research is needed to achieve effective symptom management for these patients. Design A literature review with a systematic search of symptom management in adult brain tumours. Methods Electronic data bases were searched to obtain relevant published literature on symptom management in adults with brain tumours. This was then analysed and a synthesis of relevant findings is presented. Findings Four significant general themes relating to symptom management of brain tumours in adults were identified: (1) The potential theoretical foundation related to symptom management was revealed. (2) Widely accepted validated scales or questionnaires for the assessment of single symptoms or symptom clusters were recommended. (3) Several symptom clusters and the underlying biologic mechanisms have been reported. (4) Specific symptom interventions for adults with brain tumours were collected and classified as evidence‐based or insufficient evidence. Conclusion There are still many challenges in the effective management of symptoms in adults with brain tumours. The guiding role of theoretical frameworks or models related to symptom management should be utilized in future research. Using the concept of symptom clustering for research into symptoms found in patients with brain tumours, exploring common biological mechanisms for specific symptom clusters and making full use of modern big data resources to build a strong evidence base for an effective intervention or management program may inform the management of symptoms among these patients leading to better results. No Patient or Public Contribution This is a literature review. Implications for Symptom Management The ultimate goal is obviously not only improving the survival rate of patients with brain tumours, but also enhancing their quality of life. Several important findings from our review include the theoretical foundations, validated assessment tools, the assessment of symptom clusters and the underlying biologic mechanism, and the identification of the evidence base for symptom interventions. These are of relevance for managers, researchers and practitioners and may function as a reference to help the effective symptom management for adults with brain tumours.

Abstract Background Due to the class imbalance issue faced when Alzheimer’s disease (AD) develops from normal cognition (NC) to mild cognitive impairment (MCI), present clinical practice is met with challenges regarding the auxiliary diagnosis of AD using machine learning (ML). This leads to low diagnosis performance. We aimed to construct an interpretable framework, extreme gradient boosting-Shapley additive explanations (XGBoost-SHAP), to handle the imbalance among different AD progression statuses at the algorithmic level. We also sought to achieve multiclassification of NC, MCI, and AD. Methods We obtained patient data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, including clinical information, neuropsychological test results, neuroimaging-derived biomarkers, and APOE-ε4 gene statuses. First, three feature selection algorithms were applied, and they were then included in the XGBoost algorithm. Due to the imbalance among the three classes, we changed the sample weight distribution to achieve multiclassification of NC, MCI, and AD. Then, the SHAP method was linked to XGBoost to form an interpretable framework. This framework utilized attribution ideas that quantified the impacts of model predictions into numerical values and analysed them based on their directions and sizes. Subsequently, the top 10 features (optimal subset) were used to simplify the clinical decision-making process, and their performance was compared with that of a random forest (RF), Bagging, AdaBoost, and a naive Bayes (NB) classifier. Finally, the National Alzheimer’s Coordinating Center (NACC) dataset was employed to assess the impact path consistency of the features within the optimal subset. Results Compared to the RF, Bagging, AdaBoost, NB and XGBoost (unweighted), the interpretable framework had higher classification performance with accuracy improvements of 0.74%, 0.74%, 1.46%, 13.18%, and 0.83%, respectively. The framework achieved high sensitivity (81.21%/74.85%), specificity (92.18%/89.86%), accuracy (87.57%/80.52%), area under the receiver operating characteristic curve (AUC) (0.91/0.88), positive clinical utility index (0.71/0.56), and negative clinical utility index (0.75/0.68) on the ADNI and NACC datasets, respectively. In the ADNI dataset, the top 10 features were found to have varying associations with the risk of AD onset based on their SHAP values. Specifically, the higher SHAP values of CDRSB, ADAS13, ADAS11, ventricle volume, ADASQ4, and FAQ were associated with higher risks of AD onset. Conversely, the higher SHAP values of LDELTOTAL, mPACCdigit, RAVLT_immediate, and MMSE were associated with lower risks of AD onset. Similar results were found for the NACC dataset. Conclusions The proposed interpretable framework contributes to achieving excellent performance in imbalanced AD multiclassification tasks and provides scientific guidance (optimal subset) for clinical decision-making, thereby facilitating disease management and offering new research ideas for optimizing AD prevention and treatment programs.

Abstract Avalanche and surge robustness involve fundamental carrier dynamics under high electric field and current density. They are also prerequisites of any power device to survive common overvoltage and overcurrent stresses in power electronics applications such as electric vehicles, electricity grids, and renewable energy processing. Despite tremendous efforts to develop the next-generation power devices using emerging ultra-wide bandgap semiconductors, the lack of effective bipolar doping has been a daunting obstacle for achieving the necessary robustness in these devices. Here we report avalanche and surge robustness in a heterojunction formed between the ultra-wide bandgap n-type gallium oxide and the wide-bandgap p-type nickel oxide. Under 1500 V reverse bias, impact ionization initiates in gallium oxide, and the staggered band alignment favors efficient hole removal, enabling a high avalanche current over 50 A. Under forward bias, bipolar conductivity modulation enables the junction to survive over 50 A surge current. Moreover, the asymmetric carrier lifetime makes the high-level carrier injection dominant in nickel oxide, enabling a fast reverse recovery within 15 ns. This heterojunction breaks the fundamental trade-off between robustness and switching speed in conventional homojunctions and removes a key hurdle to advance ultra-wide bandgap semiconductor devices for power industrial applications.

Abstract Background Venous thromboembolism (VTE) is a substantial contributor to the global burden of disease. Observational studies have suggested that leisure sedentary behaviours (LSB) are related to the risk of VTE; however, the causal role of LSB in VTE remains unclear. Methods Using data obtained from genome-wide association studies in the UK Biobank (N = 422,218), we identified 84, 21, and 4 single nucleotide polymorphisms (SNPs) related to sedentary television (TV) watching, computer use, and driving, respectively. These SNPs were employed as instrumental variables. Summary statistics for SNP-VTE associations was obtained from the FinnGen study (5,403 cases and 130,235 controls). Two-sample Mendelian randomisation (MR) analyses were performed using inverse-variance weighted (IVW), MR-Egger,weighted median, and weighted mode approaches. Sensitivity analyses were conducted to ensure robustness of the results. Results The main IVW approach demonstrated a positive association between the genetically predicted sedentary TV watching and the risk of VTE [odds ratio (OR):1.35, 95% confidence interval (CI):1.02—1.80, P = 0.039]. However, no significant association was observed for genetically predicted sedentary computer use or driving and VTE risk. The results from our series of sensitivity analyses, including Cochran’s Q test, MR-Egger intercept test, and MR-Pleiotropy RESidual Sum and Outlier method, further supported these findings. Conclusion This study provides evidence of an association between genetically predicted sedentary TV watching and the risk of VTE. Further studies are required to elucidate the underlying causal mechanisms.

Abstract Non-polar m-plane GaN terahertz quantum cascade laser (THz-QCL) structures have been studied. One is traditional three-well resonant-phonon (RP) design scheme. The other is two-well phonon scattering injection (PSI) design scheme. The peak gains of 41.8 and 44.2 cm−1 have been obtained at 8.2 and 7.7 THz respectively at 300 K according to the self-consistent non-equilibrium Green’s function calculation. Different from the usual GaAs two-well design, the upper and lower lasing levels are both ground states in the GaN quantum wells for the PSI scheme, mitigating the severe broadening effect for the excited states in GaN. To guide the fabrication of such devices, the doping effect on the peak gain has been analyzed. The two designs have demonstrated distinct doping density dependence and it is mainly attributed to the very different doping dependent broadening behaviors. The results reveal the possibility of GaN based THz-QCL lasing at room temperature.

Abstract Solid polymer electrolytes (SPEs) and hydrogel electrolytes were developed as electrolytes for zinc ion batteries (ZIBs). Hydrogels can retain water molecules and provide high ionic conductivities; however, they contain many free water molecules, inevitably causing side reactions on the zinc anode. SPEs can enhance the stability of anodes, but they typically possess low ionic conductivities and result in high impedance. Here, we develop a lean water hydrogel electrolyte, aiming to balance ion transfer, anode stability, electrochemical stability window and resistance. This hydrogel is equipped with a molecular lubrication mechanism to ensure fast ion transportation. Additionally, this design leads to a widened electrochemical stability window and highly reversible zinc plating/ stripping. The full cell shows excellent cycling stability and capacity retentions at high and low current rates, respectively. Moreover, superior adhesion ability can be achieved, meeting the needs of flexible devices.

Abstract Background As a practice-oriented discipline, strict adherence to reporting guidelines is particularly important in randomized controlled trial (RCT) abstracts of the nursing area. However, whether abstract reports after 2010 have complied with the Consolidated Standards of Reporting Trials for Abstracts (CONSORT-A) guideline is unclear. This study aimed to evaluate whether the publication of CONSORT-A has improved abstract reporting in nursing and explores the factors associated with better adherence to the guidelines. Methods We searched the Web of Science for 200 RCTs randomly selected from ten nursing journals. We used a data extraction form based on CONSORT-A, including 16 items, to analyze the reporting adherence to the guidelines, and the reporting rate of each item and the total score for each abstract were used to indicate adherence and overall quality score (OQS, range 0–16). A comparison of the total mean score between the two periods was made, and affecting factors were analyzed. Results In the studies we included, 48 abstracts were published pre-CONSORT-A whereas 152 post-CONSORT-A. The overall mean score for reporting adherence to 16 items was 7.41 ± 2.78 and 9.16 ± 2.76 for pre- and post-CONSORT-A, respectively (total score: 16). The most poorly reported items are “harms (0%),” “outcomes in method (8.5%),” “randomization (25%),” and “blinding (6.5%).” Items including the year of publication, impact factor, multiple center trial, word count, and structured abstract are significantly associated with higher adherence. Conclusions The adherence to abstract reporting in nursing literature has improved since the CONSORT-A era, but the overall completeness of RCT abstracts remained low. A joint effort by authors, editors, and journals is necessary to improve reporting quality of RCT abstracts.

Abstract Aim To explore the genetic effects of CYP2C8, CYP2C9, CYP2J2, and EPHX2, the key genes involved in epoxyeicosatrienoic acid processing and degradation pathways in gestational diabetes mellitus (GDM) and metabolic traits in Chinese pregnant women. Methods A total of 2548 unrelated pregnant women were included, of which 938 had GDM and 1610 were considered as controls. Common variants were genotyped using the Infinium Asian Screening Array. Association studies of single nucleotide polymorphisms (SNPs) with GDM and related traits were performed using logistic regression and multivariable linear regression analyses. A genetic risk score (GRS) model based on 12 independent target SNPs associated with GDM was constructed. Logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders including age, pre-pregnancy body mass index, history of polycystic ovarian syndrome, history of GDM, and family history of diabetes, with GRS entered both as a continuous variable and categorized groups. The relationship between GRS and quantitative traits was also evaluated. Results The 12 SNPs in CYP2C8, CYP2C9, CYP2J2, and EPHX2 were significantly associated with GDM after adjusting for covariates (all P

Given a large number of applications and complex processing procedures, how to efficiently shift and schedule tax officers to provide good services to taxpayers is now receiving more attention from tax authorities. The availability of historical application data makes it possible for tax managers to shift and schedule staff with data support, but it is unclear how to properly leverage the historical data. To investigate the problem, this study adopts a user-centered design approach. We first collect user requirements by conducting interviews with tax managers and characterize their requirements of shifting and scheduling into time series prediction and resource scheduling problems. Then, we propose Tax-Scheduler, an interactive visualization system with a time-series prediction algorithm and genetic algorithm to support staff shifting and scheduling in the tax scenarios. To evaluate the effectiveness of the system and understand how non-technical tax managers react to the system with advanced algorithms and visualizations, we conduct user interviews with tax managers and distill several implications for future system design.

Abstract Currently, the optimal lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8 + T cell (Neo-T) therapy has yet to be determined. We report a single-arm, open-label and non-randomized phase 1 study (NCT02959905) of Neo-T therapy with lymphodepletion at various dose intensity in patients with locally advanced or metastatic solid tumors that are refractory to standard therapies. The primary end point is safety and the secondary end points are disease control rate (DCR), progression-free survival (PFS), overall survival (OS). Results show that the treatment is well tolerated with lymphopenia being the most common adverse event in the highest-intensity lymphodepletion groups. Neo-T infusion-related adverse events are only grade 1–2 in the no lymphodepletion group. The median PFS is 7.1 months (95% CI:3.7-9.8), the median OS is 16.8 months (95% CI: 11.9-31.7), and the DCR is 66.7% (6/9) among all groups. Three patients achieve partial response, two of them are in the no lymphodepletion group. In the group without lymphodepletion pretreatment, one patient refractory to prior anti-PD1 therapy shows partial response to Neo-T therapy. Neoantigen specific TCRs are examined in two patients and show delayed expansion after lymphodepletion treatment. In summary, Neo-T therapy without lymphodepletion could be a safe and promising regimen for advanced solid tumors.

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTβ1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dβ1 was replaced with BTβ1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dβ1 were replaced with the wildtype BTβ1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

We investigate the magnetic and electronic properties of Co films on Fe3O4(001) achieved through epitaxial growth using magnetron sputtering. X-ray magnetic circularly dichroism measurements characterize the atomic magnetism. Compared to Co films on the MgO substrate, Co on Fe3O4 exhibits a 96% enhancement in orbital magnetic moment (from 0.25 to 0.49 µB/atom) and an increase in spin magnetic moment (from 1.37 to 1.53 µB/atom), resulting in an increased mratio(ml/ms) from 0.18 to 0.32. This enhancement of the orbital moment emerges as a consequence of the interface interaction between Co and Fe3O4. Density functional theory calculations attribute this heightened orbital magnetic moment to the robust electronic exchange interactions. Our findings not only offer insights into the modulation of magnetic and electronic characteristics in Co-based magnetic heterostructures but also provide valuable implications for the potential application of magnetic oxide/ferromagnetic heterostructures in future spintronic devices.