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Abstract Background F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). Methods This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. Results The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. Conclusions A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. Trial registration ClinicalTrials.gov: NCT04174599, on 22/11/2019.

Abstract Background Ectoine as an amino acid derivative is widely applied in many fields, such as the food industry, cosmetic manufacturing, biologics, and therapeutic agent. Large-scale production of ectoine is mainly restricted by the cost of fermentation substrates (e.g., carbon sources) and sterilization. Results In this study, Halomonas cupida J9 was shown to be capable of synthesizing ectoine using xylose as the sole carbon source. A pathway was proposed in H. cupida J9 that synergistically utilizes both WBG xylose metabolism and EMP glucose metabolism for the synthesis of ectoine. Transcriptome analysis indicated that expression of ectoine biosynthesis module was enhanced under salt stress. Ectoine production by H. cupida J9 was enhanced by improving the expression of ectoine biosynthesis module, increasing the intracellular supply of the precursor oxaloacetate, and utilizing urea as the nitrogen source. The constructed J9U-P8EC achieved a record ectoine production of 4.12 g/L after 60 h of xylose fermentation. Finally, unsterile production of ectoine by J9U-P8EC from either a glucose-xylose mixture or corn straw hydrolysate was demonstrated, with an output of 8.55 g/L and 1.30 g/L of ectoine, respectively. Conclusions This study created a promising H. cupida J9-based cell factory for low-cost production of ectoine. Our results highlight the potential of J9U-P8EC to utilize lignocellulose-rich agriculture waste for open production of ectoine.

A suitable irrigation pattern is of great significance for reducing greenhouse gas emissions. In this study, field experiments and a denitrification-decomposition (DNDC) model were used to study the global warming potential based on CH4, N2O and CO2 fluxes under flooding irrigation and controlled irrigation in paddy fields in the Erhai Lake basin. The results showed that the average value of CH4 flux under controlled irrigation was lower than that under flooding irrigation, with a reduction range of 43.21% to 48.88%, however, the average value of the N2O and CO2 fluxes from paddy field under controlled irrigation were higher than those under flooding irrigation. Controlled irrigation patterns can significantly reduce the global warming potential in paddy fields based on CH4, N2O and CO2 fluxes. Controlled irrigation can effectively reduce the global warming potential per unit yield. For water management in the Erhai Lake basin, it is recommended the controlled irrigation treatment of soil moisture with an upper limit of 100% and a lower limit of 75-85% with irrigation, and a maximum surface water depth of 150-200 mm lasting for five days after precipitation from the jointing-booting stage to the milk stage.

Abstract This study conducted a comparison of the nutritional content and lipid composition of five different varieties of quinoa (QL-1, SJ-1, SJ-2, KL-1, and KL-2) from Qinghai Province, China. Each of the five varieties exhibited varying levels of essential nutrients, including crude protein, dietary fiber, and crude fat. The QL-1 variety has the highest concentration of phytic acid, measuring 1.66 g/100 g. A non-targeted lipomics analysis discovered a total of 16 lipid categories and 383 individual lipids in quinoa. Out of the several substances, glyceride had the highest concentration, exceeding 70%, with phospholipids coming next. The percentage of fatty acids and fatty acid esters was between 5 and 11%. The glycerides in all five kinds exhibited a similar composition, with unsaturated glycerides constituting over 99% of the total glycerides. Phospholipids constituted over 11% of the overall lipid content, with lecithin comprising more than 80% and cephalin ranging from 16.70 to 18.61%. The results establish a solid basis for the utilization of quinoa in processing, particularly in lipid processing. Graphical Abstract

An enduring contribution of Richards Sparks' work has been his exploration of the relationship between a learner's first language (L1) and a language that he or she learns subsequently (L2). The present paper considers that relationship from the perspective of learners and teachers of a 'foreign' language in classroom settings. The paper first sets the broader context by looking briefly at the recently developed concept of 'translanguaging' and the more established notion of 'multilingual competence'. It then moves into the domain of the foreign language classroom. It outlines studies of how much, and why, foreign language teachers have been observed to use their students' L1 (often, in the teachers' own view, excessively). It argues that attempts to exclude the students' L1 have been not only impracticable but also misguided. It proposes a framework within which teachers can avoid the dangers of using the L1 excessively but also build on its potential as a support for learning.

Abstract The development of cost-effective and eco-friendly fertilizers is crucial for enhancing iron (Fe) uptake in crops and can help alleviate dietary Fe deficiencies, especially in populations with limited access to meat. This study focused on the application of MgFe-layered double hydroxide nanoparticles (MgFe-LDHs) as a potential solution. We successfully synthesized and characterized MgFe-LDHs and observed that 1–10 mg/L MgFe-LDHs improved cucumber seed germination and water uptake. Notably, the application of 10 mg/L MgFe-LDHs to roots significantly increased the seedling emergence rate and growth under low-temperature stress. The application of 10 mg/L MgFe-LDHs during sowing increased the root length, lateral root number, root fresh weight, aboveground fresh weight, and hypocotyl length under low-temperature stress. A comprehensive analysis integrating plant physiology, nutrition, and transcriptomics suggested that MgFe-LDHs improve cold tolerance by upregulating SA to stimulate CsFAD3 expression, elevating GA3 levels for enhanced nitrogen metabolism and protein synthesis, and reducing levels of ABA and JA to support seedling emergence rate and growth, along with increasing the expression and activity of peroxidase genes. SEM and FTIR further confirmed the adsorption of MgFe-LDHs onto the root hairs in the mature zone of the root apex. Remarkably, MgFe-LDHs application led to a 46% increase (p

ObjectiveThis study aimed to assess the knowledge, attitudes, and practices (KAP) among family caregivers of patients with cerebral infarction toward home-based care.MethodsThis web-based cross-sectional study was conducted between October 2023 and February 2024 at Yancheng Third People’s Hospital. A self-designed questionnaire was developed to collect demographic information, and assess the KAP among family caregivers of patients with cerebral infarction toward home-based care.ResultsA total of 761 questionnaires were included in the study. Among the participants, 453 (59.53%) were female, and 548 (72.01%) lived with the patients. The mean knowledge, attitudes and practices scores were 6.67 ± 1.73 (possible range: 0–9), 32.95 ± 2.46 (possible range: 9–45), and 28.64 ± 4.39 (possible range: 8–40), respectively. Path analysis showed the direct effect of knowledge on both attitudes (β = 0.885, p

This study explores the reduction of carbamates (CAs) and pyrethroids (PYs) − commonly used pesticides − in lettuce using various immersion solutions and ultrasonic processing. It also examines the role of machine learning and molecular docking in understanding the mechanisms of pesticide reduction. The results revealed that the highest reduction of both CAs and PYs exceeded 80 % on lettuce leaves. In most samples, the reduction increased with the power of ultrasonic processing and processing time. The results of machine learning models (XGBoost and SHAP) showed that during the immersion cleaning of CAs and PYs, as well as during both immersion cleaning and ultrasonic processing of CAs + PYs, the reduction was most influenced by the initial pesticide levels and immersion time. Gas Chromatography-Mass Spectrometry (GC–MS) analysis of lettuce’s wax layer identified 24 compounds, including fatty alcohols, fatty acids, fatty acid esters, and triterpenoids. Despite the absence of active sites, the lipophilic nature of long-chain aliphatic compounds aids in pesticide binding, while triterpenoids form strong hydrogen bonds with pesticides, indicating a robust adsorption on the lettuce surface. This study aims to offer insights into the efficient removal of chemical pesticide residues from fruits and vegetables, addressing critical concerns for food safety and human health.

Objectives: Effective exclusion of low-risk symptomatic outpatient cases for colorectal cancer (CRC) remains diagnostic challenges. We aimed to develop a self-reported symptom-based decision-making model for application in outpatient scenarios. Methods: In total, 8233 symptomatic cases at risk for CRC, as judged by outpatient physicians, were involved in this study at seven medical centers. A decision-making model was constructed using 60 self-reported symptom parameters collected from the questionnaire. Further internal and external validation cohorts were built to evaluate the discriminatory power of the CRC model. The discriminatory power of the CRC model was assessed by the C-index and calibration plot. After that, the clinical utility and user experience of the CRC model were evaluated. Results: Nine symptom parameters were identified as valuable predictors used for modeling. Internal and external validation cohorts verified the adequate discriminatory power of the CRC model. In the clinical application step, all 17 physicians found the model easy to grasp, 99.9 % of the patients were satisfied with the survey form. Application of this model detected all CRC cases. The total consistency ratio of outpatient cases undergoing colonoscopy was 81.4 %. None of the low-risk patients defined by the CRC model had been diagnosed with CRC. Conclusion: This multicenter study developed and validated a simple and user-friendly decision-making model covering self-reported information. The CRC model has been demonstrated to perform well in terms of rapid outpatient decision-making scenarios and clinical utility, particularly because it can better rule out low-risk outpatient cases.

Bi(Te, Se)-based compounds have attracted lots of attention for nearly two centuries as one of the most successful commercial thermoelectric (TE) materials due to their high performance at near room temperature. Compared with 3D bulks, 2D thin films are more compatible with modern semiconductor technology and have unique advantages in the construction of micro- and nano-devices. For device applications, high average TE performance over the entire operating temperature range is critical. Herein, highly c-axis-oriented N-type Bi(Te, Se) epitaxial thin films have been successfully prepared using the pulsed laser deposition technology by adjusting the deposition temperature. The film deposited at ∼260 °C demonstrate a remarkable average power factor (PFave) of ∼24.4 μW·cm−1·K−2 over the temperature range of 305–470 K, higher than most of the state-of-the-art Bi(Te, Se)-based films. Moreover, the estimated average zT value of the film is as high as ∼0.81. We then constructed thin-film TE devices by using the above oriented Bi(Te, Se) films, and the maximum output power density of the device can reach up to ∼30.1 W/m2 under the temperature difference of 40 K. Predictably, the outstanding average TE performance of the highly oriented Bi(Te, Se) thin films will have an excellent panorama of applications in semiconductor cooling and power generation.

Abstract Background To investigate the knowledge, attitude, and practice (KAP) of healthcare professionals regarding cognitive dysfunction and cognitive rehabilitation in Parkinson’s disease (PD). Methods This multicenter, cross-sectional survey enrolled physicians and nurses in 10 hospitals between October 2022 and November 2022. A self-administered questionnaire was developed to collect the demographic information of the participants and their knowledge, attitude, and practice toward cognitive dysfunction in PD and cognitive rehabilitation. Results This study enrolled 224 physicians and 229 nurses. The knowledge, attitude, and practice scores were 12.57 ± 3.76 (total score: 22), 29.10 ± 3.71 (total score: 32), and 21.07 ± 8.03 (total score: 28) among physicians, and 9.97 ± 4.70 (total score: 22), 25.27 ± 8.96 (total score: 32), and 25.27 ± 8.96 (total score: 28) among nurses. Among physicians, the knowledge scores (OR = 4.23, 95%CI: 2.36–7.58, P

Our previous study showed that magnetic field pretreatment promoted germination and phenolic enrichment in quinoa. In this study, we further investigated the effects of NaCl stress on the growth and phenolic synthesis of germinated quinoa after magnetic field pretreatment (MGQ). The results showed that NaCl stress inhibited the growth of MGQ, reduced the moisture content and weight of a single plant, but increased the fresh/dry weight. The higher the NaCl concentration, the more obvious the inhibition effect. In addition, NaCl stress inhibited the hydrolysis of MGQ starch, protein, and fat but increased the ash content. Moreover, lower concentrations (50 and 100 mM) of NaCl stress increased the content of MGQ flavonoids and other phenolic compounds. This was due to the fact that NaCl stress further increased the enzyme activities of PAL, C4H, 4CL, CHS, CHI, and CHR and up-regulated the gene expression of the above enzymes. NaCl stress at 50 and 100 mM increased the DPPH and ABTS scavenging capacity of MGQ and increased the activities of antioxidant enzymes, including SOD, POD, CAT, APX, and GSH-Px, further enhancing the antioxidant system. Furthermore, principal component analysis showed that NaCl stress at 100 mM had the greatest combined effect on MGQ. Taken together, NaCl stress inhibited the growth of MGQ, but appropriate concentrations of NaCl stress, especially 100 mM, helped to further increase the phenolic content of MGQ and enhance its antioxidant system.

ABSTRACT Malignant central airway stenosis is treated with airway stent placement, but post-placement microbial characteristics remain unclear. We studied microbial features in 60 patients post-stent placement, focusing on changes during granulation tissue proliferation. Samples were collected before stent (N = 29), after stent on day 3 (N = 20), and after granulation tissue formation (AS-GTF, N = 43). Metagenomic sequencing showed significant respiratory tract microbiota changes with granulation tissue. The microbiota composition, dominated by Actinobacteria, Firmicutes, and Proteobacteria, was similar among the groups. At the species level, the AS-GTF group exhibited significant differences, with Peptostreptococcus stomatis and Achromobacter xylosoxidans enriched. Analysis based on tracheoesophageal fistula presence identified Tannerella forsythia and Stenotrophomonas maltophilia as the main differential species, enriched in the fistula subgroup. Viral and fungal detection showed Human gammaherpesvirus 4 and Candida albicans as the main species, respectively. These findings highlight microbiota changes after stent placement, potentially associated with granulation tissue proliferation, informing stent placement therapy and anti-infective treatment optimization.IMPORTANCEMalignant central airway stenosis is a life-threatening condition that can be effectively treated with airway stent placement. However, despite its clinical importance, the microbial characteristics of the respiratory tract following stent insertion remain poorly understood. This study addresses this gap by investigating the microbial features in patients with malignant central airway stenosis after stent placement, with a specific focus on microbial changes during granulation tissue proliferation. The findings reveal significant alterations in the diversity and structure of the respiratory tract microbiota following the placement of malignant central airway stents. Notably, certain bacterial species, including Peptostreptococcus stomatis and Achromobacter xylosoxidans, exhibit distinct patterns in the after-stent granulation tissue formation group. Additionally, the presence of tracheoesophageal fistula further influences the microbial composition. These insights provide valuable references for optimizing stent placement therapy and enhancing clinical anti-infective strategies.

Abstract Objectives Several clinical trials have evaluated the efficacy and safety of baricitinib in COVID-19 patients. Recently, there have been reports on critical patients, which are different from previous research results. The meta-analysis was performed to investigate the effects of baricitinib in COVID-19, by pooling data from all clinically randomized controlled trials (RCTs) available to increase power to testify. Methods Studies were searched in PubMed, Embase, and Cochrane Library databases on January 31, 2023. We performed a meta-analysis to estimate the efficacy and safety of baricitinib for the treatment of hospitalized adults with COVID-19. This study is registered with INPLASY, number 202310086. Results A total of 3010 patients were included in our analyses. All included studies were randomized controlled trials or prospective study. There was no difference in 14-day mortality between the two groups [OR 0.23 (95% CI 0.03–1.84), I 2 = 72%, P = 0.17]. In subgroup analyses we found that baricitinib did not seem to improve significantly in 24-day mortality critically ill patients [OR 0.60 (95% CI 0.35–1.02), I 2 = 0%, P = 0.06]. Fortunately, baricitinib have led to faster recovery and shorter hospital stays for COVID-19 patients. There were no difference in infections and infestations, major adverse cardiovascular events, deep vein thrombosis and pulmonary embolism. Conclusions Baricitinib did not increase the incidence of adverse reactions. At the same time, we can find that it reduces the mortality of COVID-19 patients, not including the critically ill.

In order to address the increasingly prominent issues of water resource protection and agricultural non-point source pollution in the Erhai Lake Basin, this study conducted a two-year field experiment in Gusheng Village, located in the Erhai Lake Basin. In 2022, two irrigation treatments were set up: conventional flooding irrigation (CK) and controlled irrigation (C), with three replicates for each treatment. In 2023, aiming to enhance the utilization rate of rainwater resources and reduce the direct discharge of dry-farming tailwater from upstream into Erhai Lake. The paddy field was used as an ecological storage basin, and the water storage depth of the paddy field was increased compared to the depth of 2022. Combined with the deep storage of rainwater, the dry-farming tailwater was recharged into the paddy field to reduce the drainage. In 2023, two water treatments, flooding irrigation with deep storage and controlled drainage (CKCD) and water-saving irrigation with deep storage and controlled drainage (CCD) were set up, and each treatment was set up with three replicates. The growth and physiological index of rice at various stages were observed. Nitrogen leaching of paddy field in surface water, soil water, and groundwater under different water treatments after tillering fertilizer were observed. The research results show that the combined application of organic and inorganic fertilizers under organic planting can provide more reasonable nutrient supply for rice, promote dry matter accumulation and other indices, and also reduce the concentration of NH4+-N in surface water. Compared with CK, the yield, 1000-grain weight, root-to-shoot ratio, and leaf area index of C are increased by 4.8%, 4.1%, 20.9%, and 9.7%, respectively. Compared with CKCD, the yield, 1000-grain weight, root-to-shoot ratio, and leaf area index of CCD are increased by 6.5%, 3.8%, 19.6%, and 21.9%, respectively. The yield in 2023 is 19% higher than that in 2022. Treatment C can increase the growth indicators and reduce the net photosynthetic rate to a certain extent, while CCD rain-flood storage can alleviate the inhibition of low irrigation lower limit on the net photosynthetic rate of rice. Both C and CCD can reduce nitrogen loss and irrigation amount in paddy fields. CCD can reduce the tailwater in the Gusheng area of the Erhai Lake Basin to Erhai Lake, and also can make full use of N, P, and other nutrients in the tailwater to promote the formation and development of rice. In conclusion, the paddy field rain-flood storage methodology in the Erhai Lake Basin can promote various growth and physiological indicators of rice, improve water resource utilization efficiency, reduce direct discharge of tailwater into Erhai Lake, and decrease the risk of agricultural non-point source pollution.

Ganoderma lingzhi, a species of white rot fungus, possesses the highest abundance of lignocellulose-degrading enzymes among these fungi, as well as a relatively high carbon conversion rate. Corn straw, as an important sustainable resource, is used as a substrate for the liquid culture of G. lingzhi. However, little is known about the genes encoding the lignocellulose degradation and polysaccharide and triterpenoid biosynthetic pathways involved in this process. This paper employs transcriptomics to uncover the key genes involved in lignocellulose degradation and the synthesis of polysaccharides and triterpenoids during the liquid fermentation of G. lingzhi using corn straw as the substrate, as well as their associations. Carbohydrate-Active enzymes analysis of differential genes in the sequencing results was used to analyze the genes related to lignocellulose degradation. Among these, 43 core genes encoding CAZymes were obtained after 0 to 5 days of fermentation, and 25 core genes encoding CAZymes were obtained after 5 to 12 days of fermentation. The differential expression levels of DN3690_c0_g1 (EGL), DN3627_c0_g2 (XYN), DN4778_c0_g1 (XYN), DN2037_c0_g1 (LACC), and DN277_c2_g1 (MnP) were used to identify the key genes. The polysaccharide synthesis metabolic pathway favored mannitol synthesis, and the expression of triterpene precursor-metabolizing enzyme genes revealed higher expression levels of key enzyme genes such as ACAT, HMGS, and MPK. A correlation clustering analysis of genes related to lignocellulose degradation, polysaccharide, and triterpene anabolism during liquid fermentation showed that lignocellulose degradation genes mainly influenced arabinose and mannitol anabolism, as well as the synthesis of triterpene precursors.

Abstract We previously confirmed that a strain of Lactobacillus oris isolated from the fecal samples of healthy Hainan centenarian having potent lipid-lowering ability in HepG2 cells; and this study was to investigate the effect of the stain on non-alcoholic fatty liver in mice in vivio. The Lactobacillus oris strain isolated from Hainan centenarian fecal samples were frozen stored in our laboratory. Thirty ob/ob mice (10 in each group) were orally gavaged with Lactobacillus oris (Lactobacillus, 5 × 109 cfu), mixed probiotics (Mixed, 5 × 109 cfu, a mixture with known lipid-lowering ability), or culture medium (Control) respectively. Lactobacillus oris isolated from fecal samples of Hainan centenarians showed significantly in vivo lipid lowering ability compared with the controls, and the ability was comparable with mixed probiotics strains in mice The possible mechanisms of lipid-lowering of probiotics and Lactobacillus oris may be associated with HMGR inhibition to suppress the synthesis of endogenous cholesterol; bile acids reabsorption, and intestinal FXR-FGF15 signaling pathways promoting the cholesterol conversion into bile acids secretion.

Abstract The conversion of lignocellulosic feedstocks to fermentable sugar for biofuel production is inefficient, and most strategies to enhance efficiency directly target lignin biosynthesis, with associated negative growth impacts. Here we demonstrate, for both laboratory- and field-grown plants, that expression of Pag-miR408 in poplar (Populus alba × P. glandulosa) significantly enhances saccharification, with no requirement for acid-pretreatment, while promoting plant growth. The overexpression plants show increased accessibility of cell walls to cellulase and scaffoldin cellulose-binding modules. Conversely, Pag-miR408 loss-of-function poplar shows decreased cell wall accessibility. Overexpression of Pag-miR408 targets three Pag-LACCASES, delays lignification, and modestly reduces lignin content, S/G ratio and degree of lignin polymerization. Meanwhile, the LACCASE loss of function mutants exhibit significantly increased growth and cell wall accessibility in xylem. Our study shows how Pag-miR408 regulates lignification and secondary growth, and suggest an effective approach towards enhancing biomass yield and saccharification efficiency in a major bioenergy crop.

Abstract Passivating contactsin heterojunction (HJ) solar cells have shown great potential in reducing recombination losses, and thereby achieving high power conversion efficiencies in photovoltaic devices. In this direction, carbon nanomaterials have emerged as a promising option for carbon/silicon (C/Si) HJsolar cells due to their tunable band structure, wide spectral absorption, high carrier mobility, and properties such as multiple exciton generation. However, the current limitations in efficiency and active area have hindered the industrialization of these devices. In this review, they examine the progress made in overcoming these constraints and discuss the prospect of achieving high power conversion efficiency (PCE) C/Si HJ devices. A C/Si HJ solar cell is also designed by introducing an innovative interface passivation strategy to further boost the PCE and accelerate the large area preparationof C/Si devices. The physical principle, device design scheme, and performanceoptimization approaches of this passivated C/Si HJ cells are discussed. Additionally, they outline potential future pathways and directions for C/Si HJ devices, including a reduction in their cost to manufacture and their incorporation intotandem solar cells. As such, this review aims to facilitate a deeperunderstanding of C/Si HJ solar cells and provide guidance for their further development.

Background: Sex differences in health status and life expectancy are widely accepted to exist. The mechanisms underlying it are still poorly understood. In this study, we aimed to clarify the influences and contributions of sex on the gut microbiome in healthy centenarians and to explore the different roles played by the gut microbiome in healthy aging between the sexes. Results: Taking covariates of different dimensions into account (social demographics, anthropometry, the activities of daily living, dietary structure, mental state, blood tests, lifestyle and disease history), our data showed that sex was one of the most significant covariates affecting the gut microbiome of healthy centenarians at both the species and Kyoto Encyclopedia of Genes and Genomes Orthology (KO) levels. The beta diversity between the sexes were significantly different (Adonis test: p = 0.011, R2 = 0.031), and the male centenarians had a greater alpha diversity than the females (Simpson and Shannon test: P

Conducting functional assessments remotely can help alleviate the burden of in-person assessment on patients with Duchenne muscular dystrophy and their caregivers. The objective of this study was to evaluate whether scores from remote functional assessment of patients with Duchenne muscular dystrophy correspond to in-person scores on the same functional assessments. Remote live stream versus in-person scores on the North Star Ambulatory Assessment (including time [seconds] to complete the 10-meter walk/run and time to rise from the floor [supine to stand]) were assessed using statistical analyses, including intraclass correlation coefficient, and Pearson, Spearman, and Bland-Altman analyses. The remote and in-clinic assessments had to occur within 2 weeks of one another to be considered for this analysis. This analysis included patients with Duchenne muscular dystrophy, aged 4 to 7 years. Participants in this analysis received delandistrogene moxeparvovec (as part of SRP-9001-101 [Study 101; NCT03375164] or SRP-9001-102 [Study 102; NCT03769116]) or were randomized to receive placebo (in Part 1 of Study 102). This study evaluates score reproducibility between live stream remote scoring versus in-person functional assessments as determined by intraclass correlation coefficient, and Pearson, Spearman, and Bland-Altman analyses. The results showed that scores from remote functional assessment of patients with Duchenne muscular dystrophy strongly correlated with those obtained in person. These findings demonstrate congruence between live stream remote and in-person functional assessment and suggest that remote assessment has the potential to reduce the burden on a family by supplementing in-clinic visits.

Background: The novel biologic agent ustekinumab (UST), a monoclonal antibody against the p40 subunit of interleukin-12 and interleukin-23, has been applied in the treatment of Crohn’s disease (CD). With the development of relevant research, the clinical treatment and favorable prognosis of UST in CD have garnered considerable attention. However, there is a lack of reports that present the current status of UST-related studies in a comprehensive and objective manner. Consequently, this study aims to visually analyze the current status and clinical trends of UST-related research, identify leading researchers, and recognize deficiencies using bibliometrics and knowledge mapping, which might assist in understanding future research priorities in that specific field.Methods: Published articles containing the use of UST in CD were retrieved from the Web of Science core collection database between 2008 and 2022. Then, the bibliometric analysis was performed, and a knowledge map was generated and visualized using the CiteSpace software.Results: A total of 479 articles published between 2008 and 2022 were included in the bibliometric analysis. These publications were authored by 185 scholars from 51 countries or regions, among which the United States (38.3%), Canada (16.9%) and England (10.0%) were predominant in publishing. The keyword analysis indicated that UST has long been a popular biologic agent, and its clinical efficacy, safety, and indication for vulnerable populations in CD are popular research topics. The phrase “fecal calprotectin,” a biomarker reflecting the degree of disease activity and monitoring the therapeutic response, began to gain traction in 2020 and has continued to this day. Looking for UST-related biomarkers was gaining clinical attention.Conclusion: The number of clinical studies involving the outcome of UST treatment in CD patients has increased, with the current research focusing on efficacy, safety, indications for vulnerable populations, therapeutic drug monitoring, and biomarkers. As an alternative drug after the failure of traditional immunosuppressive therapies or TNF-α antagonist therapy, UST is an effective and safe therapy in real-world refractory CD patients. UST will remain an active candidate for research in the treatment of CD.

Abstract Single-cell RNA sequencing methods focusing on the 5′-end of transcripts can reveal promoter and enhancer activity and efficiently profile immune receptor repertoire. However, ultra-high-throughput 5′-end single-cell RNA sequencing methods have not been described. We introduce FIPRESCI, 5′-end single-cell combinatorial indexing RNA-Seq, enabling massive sample multiplexing and increasing the throughput of the droplet microfluidics system by over tenfold. We demonstrate FIPRESCI enables the generation of approximately 100,000 single-cell transcriptomes from E10.5 whole mouse embryos in a single-channel experiment, and simultaneous identification of subpopulation differences and T cell receptor signatures of peripheral blood T cells from 12 cancer patients.

Iron ore tailings from iron ore mines pose environmental challenges. However, their reuse could provide significant environmental benefits. This study focused on producing clean concrete using iron ore tailings as crushed stone aggregate (IOTA) and calcium carbonate whiskers (CWs) as reinforcement. Five mixture groups were prepared: normal concrete (NAC) with natural crushed stone aggregate (NA), iron ore tailings concrete (TAC) with IOTA, and CW (10%, 20%, and 30%)-reinforced TAC (TAC-CW). Mechanical properties like the compressive strength (fcu) and splitting tensile strength (fst), as well as sulfate freeze–thaw (F-T) cycle resistance, were thoroughly investigated. Additionally, pore structure and microstructure were characterized using nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM) techniques. The results showed that IOTA’s complete replacement of NA decreased concrete mechanical properties and frost resistance, but incorporating CWs effectively compensated for these losses. Specifically, the fcu and fst of TAC-CW20 with 20% CWs increased by 23.26% and 49.6% compared to TAC and were higher than those of NAC. With increasing F-T cycles, concrete internal pore structure significantly deteriorated, and corrosive products increased significantly, which was further confirmed by SEM. TAC-CW20 significantly optimized pore structure. Overall, the successful application of iron ore tailings as eco-friendly materials enhanced concrete performance and reduced the environmental impact of construction activities.

The aim of this research is to investigate which CALL glossing modes (text only, text plus audio, and text plus video clips) are effective for learners' idiom acquisition. Ninety-nine intermediate-level first-year students from a university in China were divided into three groups. In order to determine if CALL glossing had any effect on students' idiom learning, pre- and post-idiom tests were administered. In addition, all the participants completed a questionnaire and five participants from each group completed face-to-face interviews to understand learners' perceptions of different CALL glosses. The results indicated that all three glossing modes promoted idiom acquisition; specifically, text with video glossing mode was more effective than text plus audio glosses and text only glossing mode. These results offer pedagogical implications for idiom teaching and learning, and also provide valuable insights for education in the future.

Abstract Objective To explore the factors correlated with excessive daytime sleepiness (EDS) in patients with Parkinson's disease (PD). Methods A total of 239 PD patients were divided into two groups based on the presence of EDS (Epworth Sleepiness Scale score≥10) (PD‐EDS vs. PD‐non‐EDS). Participants underwent an extensive assessment to determine demographic features, disease severity, polysomnography characteristics, and nonmotor symptoms. Results Of the 239 patients, 56 patients (23.4%) were classified as having PD combined with EDS. Binary logistic regression analysis showed that fatigue (Fatigue Severity Scale [FSS] score ≥4) (odds ratio [OR] [95% CI] = 4.897 [2.376–10.095], p

Xuanfeibaidu Formula (XFBD) is a Chinese medicine used in the clinical treatment of coronavirus disease 2019 (COVID-19) patients. Although XFBD has exhibited significant therapeutic efficacy in clinical practice, its underlying pharmacological mechanism remains unclear. Here, we combine a comprehensive research approach that includes network pharmacology, transcriptomics, and bioassays in multiple model systems to investigate the pharmacological mechanism of XFBD and its bioactive substances. High-resolution mass spectrometry was combined with molecular networking to profile the major active substances in XFBD. A total of 104 compounds were identified or tentatively characterized, including flavonoids, terpenes, carboxylic acids, and other types of constituents. Based on the chemical composition of XFBD, a network pharmacology-based analysis identified inflammation-related pathways as primary targets. Thus, we examined the anti-inflammation activity of XFBD in a lipopolysaccharide-induced acute inflammation mice model. XFBD significantly alleviated pulmonary inflammation and decreased the level of serum proinflammatory cytokines. Transcriptomic profiling suggested that genes related to macrophage function were differently expressed after XFBD treatment. Consequently, the effects of XFBD on macrophage activation and mobilization were investigated in a macrophage cell line and a zebrafish wounding model. XFBD exerts strong inhibitory effects on both macrophage activation and migration. Moreover, through multimodal screening, we further identified the major components and compounds from the different herbs of XFBD that mediate its anti-inflammation function. Active components from XFBD, including Polygoni cuspidati Rhizoma, Phragmitis Rhizoma, and Citri grandis Exocarpium rubrum, were then found to strongly downregulate macrophage activation, and polydatin, isoliquiritin, and acteoside were identified as active compounds. Components of Artemisiae annuae Herba and Ephedrae Herba were found to substantially inhibit endogenous macrophage migration, while the presence of ephedrine, atractylenolide I, and kaempferol was attributed to these effects. In summary, our study explores the pharmacological mechanism and effective components of XFBD in inflammation regulation via multimodal approaches, and thereby provides a biological illustration of the clinical efficacy of XFBD.

Carbon/silicon heterojunctions provide a new perspective for silicon solar cells and in particular those made from carbon nanotubes (CNTs) have already achieved industrial‐level power conversion efficiency and device size when using organic passivation and a back‐junction design. However, the current state of the art device geometry for silicon photovoltaics is the interdigitated back contact (IBC) cell and this has yet to be demonstrated for CNT/Si solar cells due to the complexity of fabricating the required patterns. Herein, IBC‐CNT solar cells are demonstrated via the simple spin coating of a conductive hole‐selective passivating film and the evaporation of buried silicon oxide/magnesium electron‐selective contacts for both polarities. The CNT coverage area fraction (fCNT) and the gap between the two polarities are optimized to minimize electrical shading loss and ensure high photocarrier collection. Large‐area (4.76 cm2) highly efficient (17.53%) IBC‐CNT solar cells with a Voc of 651 mV and Jsc of 40.56 mA cm−2 are demonstrated and are prepared with one alignment step for the CNT/Si contact, and photolithographic‐free and room‐temperature processes. These performance parameters are among the best for solution‐processed dopant‐free IBC schemes and indicate the feasibility of using low‐dimensional carbon materials in IBC solar cells.

Small-diameter vascular grafts (SDVGs) are urgently required for clinical applications. Constructing vascular grafts mimicking the defining features of native arteries is a promising strategy. Here, we constructed a tri-layered vascular graft with a native artery decellularized extracellular matrix (dECM) mimicking the component of arteries. The porcine thoracic aorta was decellularized and milled into dECM powders from the differential layers. The intima and media dECM powders were blended with poly (L-lactide-co-caprolactone) (PLCL) as the inner and middle layers of electrospun vascular grafts, respectively. Pure PLCL was electrospun as a strengthening sheath for the outer layer. Salidroside was loaded into the inner layer of vascular grafts to inhibit thrombus formation. In vitro studies demonstrated that dECM provided a bioactive milieu for human umbilical vein endothelial cell (HUVEC) extension adhesion, proliferation, migration, and tube-forming. The in vivo studies showed that the addition of dECM could promote endothelialization, smooth muscle regeneration, and extracellular matrix deposition. The salidroside could inhibit thrombosis. Our study mimicked the component of the native artery and combined it with the advantages of synthetic polymer and dECM which provided a promising strategy for the design and construction of SDVGs.

Introduction: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy designed for targeted expression of SRP-9001 dystrophin protein, a shortened dystrophin retaining key functional domains of the wild-type protein.Methods: This Phase 2, double-blind, two-part (48 weeks per part) crossover study (SRP-9001-102 [Study 102]; NCT03769116) evaluated delandistrogene moxeparvovec in patients, aged ≥4 to

In recent years, quinoa, as a nutritious and sustainable food material, has gained increasing popularity worldwide. To investigate the diversity of nutritional characteristics among different quinoa cultivars and explore their potential health benefits, metabolites of five quinoa cultivars (QL-1, SJ-1, SJ-2, KL-1 and KL-2) were compared by non-targeted metabolomics analysis based on UPLC-ZenoTOF-MS/MS in this study. A total of 248 metabolites across 13 categories were identified. Although the metabolite compositions were generally similar among the different quinoa cultivars, significant variations existed in their respective metabolite contents. Among the identified metabolites, amino acids/peptides, nucleosides, saponins and phenolic acids were the most abundant. Notably, SJ-1 exhibited the most distinct metabolite profile when compared to the other cultivars. Amino acids/peptides and nucleosides were found to be crucial factors contributing to the unique metabolite profile of SJ-1. Collectively, these aforementioned metabolites accounted for a substantial 60% of the total metabolites observed in each quinoa variety. Additionally, a correlation between the DPPH radical scavenging activity and the free phenolic content of quinoa was observed. Variations in phenolic content resulted in different antioxidant capacities among the quinoa cultivars, and SJ-1 exhibited lower phenolic levels and weaker antioxidant activity than the others. These results can provide important information for the development of quinoa resources.

The two-dimensional electron gas (2DEG) generated at the LaAlO3/SrTiO3 interface has been in the focus of oxides research since its first discovery. Although oxygen vacancies play an important role in the generation of the insulator-to-metal transition of the SrTiO3 bare surface, their contribution at the LaAlO3/SrTiO3 interface remains unclear. In this work, we investigated a LaAlO3/SrTiO3 heterostructure with regional distribution of defect-based localized polar sites at the interface. Using static and time-resolved threshold photoemission electron microscopy, we prove that oxygen vacancies are induced near those polar sites, resulting in the increase of carrier density of the 2DEG states. In addition, oxygen-related surface states were uncovered, which we attributed to the release of lattice oxygen during the formation of oxygen vacancies. Such effects are mainly found spatially located around the defect sites at the buried interface, while other regions remain unaffected. Our results confirm that the itinerant electrons induced by oxygen vacancies can coexist with the charge transfer mechanism in the LaAlO3/SrTiO3 heterostructure, together leading to the formation of the metallic interface. These observations provide fundamental insights into the nature of LaAlO3/SrTiO3 interface based 2DEG and unique perspectives for potential applications.

Background As life expectancy increases, the number of elderly patients with osteoporosis rises as well. Many factors affect the development of osteoporosis, and good physical fitness may contribute to having better social adaptability in older people. So it is very important to pay attention to osteoporosis and ensure physical fitness in this group. Objective To explore the factors associated with osteoporosis, and analyze physical fitness in elderly men, providing a theoretical basis for preventing osteoporosis, improving physical fitness and developing health management programs for this group. Methods This study was conducted from January 2018 to December 2020. A total of 250 elderly men who underwent bone mineral density (BMD) examination were selected from Health Management Center, Inner Mongolia People's Hospital, and divided into normal BMD, osteopenia and osteoporosis groups by BMD examination results. Data were collected, including baseline information, laboratory results, physical fitness test results〔 including muscular strength (number of elbow bending within 30 seconds, 30-second sit-to-stand test results) , flexibility (shoulder and arm stretches, sitting flexion test) , balance (stand on one foot with eyes closed) , aerobic capacity (2-minute step test) , agility/mobility (timed up go test with a minimal space of 2.5 meters) 〕. Results Of the 250 subjects, 76 (30.4%) had normal BMD, 123 (49.2%) had osteopenia, and 51 (20.4%) had osteoporosis. Multivariate Logistic regression analysis demonstrated that abdomen circumference〔OR=0.710, 95%CI (0.566, 0.891) 〕, body mass index 〔OR=0.685, 95%CI (0.474, 0.990) 〕, high-density lipoprotein cholesterol〔OR=74.182, 95%CI (3.738, 1 472.125) 〕, 25 (OH) D3〔OR=0.745, 95%CI (0.619, 0.897) 〕, and estradiol〔OR=0.784, 95%CI (0.665, 0.924) 〕were associated with osteoporosis in elderly men (P0.05) . Conclusion In elderly men, abdomen circumference, body mass index, high-density lipoprotein cholesterol, 25 (OH) D3, and estradiol may independently associated with osteoporosis. Physical fitness indices varied significantly by BMD, especially flexibility, balance, aerobic capacity and agility/mobility.

Abstract The gut microbes play important roles in human longevity and the gut microbiota profile of centenarians shows some unique features from young adults. Nowadays, most microbial studies on longevity are commonly based on metagenomic sequencing which may lose information about the functional microbes with extremely low abundance. Here, we combined in-depth metagenomic sequencing and large-scale culturomics to reveal the unique gut microbial structure of a Chinese longevity population, and to explore the possible relationship between intestinal microbes and longevity. Twenty-five healthy Hainan natives were enrolled in the study, including 12 centenarians and 13 senior neighbors. An average of 51.1 Gb raw sequencing data were obtained from individual fecal sample. We assembled 1778 non-redundant metagenomic assembled genomes (MAGs), 33.46% of which cannot be classified into known species. Comparison with the ordinary people in Hainan province, the longevous cohort displayed significantly decreased abundance of butyrate-producing bacteria and largely increased proportion of Escherichia coli, Desulfovibrio piger and Methanobrevibacter smithii. These species showed a constant change with aging. We also isolated 8,030 strains from these samples by large-scale culturomics, most of which belonged to 203 known species as identified by MALDI-TOF. Surprisingly, only 42.17% of the isolated species were also detected by metagenomics, indicating obvious complementarity between these two approaches. Combination of two complement methods, in-depth metagenomic sequencing and culturomics, provides deeper insights into the longevity-related gut microbiota. The uniquely enriched gut microbes in Hainan extreme decades population may help to promote health and longevity.

Abstract Background AdpA is a global regulator of morphological differentiation and secondary metabolism in Streptomyces, but the regulatory roles of the Streptomyces AdpA family on the biosynthesis of the natural product ε-poly-l-lysine (ε-PL) remain unidentified, and few studies have focused on increasing the production of ε-PL by manipulating transcription factors in Streptomyces. Results In this study, we revealed the regulatory roles of different AdpA homologs in ε-PL biosynthesis and morphological differentiation and effectively promoted ε-PL production and sporulation in Streptomyces albulus NK660 by heterologously expressing adpA from S. neyagawaensis NRRLB-3092 (adpA Sn ). First, we identified a novel AdpA homolog named AdpA Sa in S. albulus NK660 and characterized its function as an activator of ε-PL biosynthesis and morphological differentiation. Subsequently, four heterologous AdpA homologs were selected to investigate their phylogenetic relationships and regulatory roles in S. albulus, and AdpA Sn was demonstrated to have the strongest ability to promote both ε-PL production and sporulation among these five AdpA proteins. The ε-PL yield of S. albulus heterologously expressing adpA Sn was approximately 3.6-fold higher than that of the control strain. Finally, we clarified the mechanism of AdpA Sn in enhancing ε-PL biosynthesis and its effect on ε-PL polymerization degree using real-time quantitative PCR, microscale thermophoresis and MALDI-TOF–MS. AdpA Sn was purified, and its seven direct targets, zwf, tal, pyk2, pta, ack, pepc and a transketolase gene (DC74_2409), were identified, suggesting that AdpA Sn may cause the redistribution of metabolic flux in central metabolism pathways, which subsequently provides more carbon skeletons and ATP for ε-PL biosynthesis in S. albulus. Conclusions Here, we characterized the positive regulatory roles of Streptomyces AdpA homologs in ε-PL biosynthesis and their effects on morphological differentiation and reported for the first time that AdpA Sn promotes ε-PL biosynthesis by affecting the transcription of its target genes in central metabolism pathways. These findings supply valuable insights into the regulatory roles of the Streptomyces AdpA family on ε-PL biosynthesis and morphological differentiation and suggest that AdpA Sn may be an effective global regulator for enhanced production of ε-PL and other valuable secondary metabolites in Streptomyces.

Emodin, derived from Rheum officinale and aloe, is known for its diverse benefits such as antiinflammatory, antioxidant, and antibacterial properties. Currently, the impact of emodin on urosepsis is unclear. This study aims to investigate the mechanism of action of emodin in urosepsis. Peripheral blood mononuclear cells (PBMCs) were purchased from Cloud-Clone Animal Inc. and treated with emodin. Cell viability and the lactate dehydrogenase (LDH) level were then assessed. In a separate experiment, a urosepsis model was established in Sprague Dawley rats which were subsequently treated with emodin. The levels of oxidative stress-related factors, serum complements and inflammatory factors were measured using commercial kits. Blood urea nitrogen and serum creatinine levels were determined using a fully automatic biochemical analyzer. The levels of pro-inflammatory proteins and AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) pathway-related proteins were evaluated via Western blot. PBMCs were unaffected by emodin concentrations below 60 μg/mL, and minimal LDH levels were detected in the cells. Emodin attenuated the effects of Escherichia coli and diminished the production of serum complements, oxidative stress-related proteins, and inflammatory factors in PBMCs. Notably, the effects of emodin were lessened by an AMPK pathway inhibitor. Additionally, emodin alleviated oxidative stress, complement system activation, inflammation, and kidney injury in urosepsis rats through the AMPK/SIRT1 signaling pathway. Emodin improved kidney damage in urosepsis rats by activating the AMPK/SIRT1 signaling pathway, which reduced oxidative stress, inflammation, and complement system activation. [ABSTRACT FROM AUTHOR]

The 1 sun-heating temperatures of photothermal materials can be generally elevated from ~90 °C to ~300 °C by hybridizing with infrared insulating materials, capable of driving methanol reforming to 310 mmol g−1 h−1 over CuOx/ZnO/Al2O3 nanosheets.

The main hurdle to the upgradation of photovoltaic industry is the large performance losses that the tunnel oxide passivated contact (TOPCon) and silicon heterojunction (SHJ) cells have during the cutting and separating process for the assembly of shingle solar panels. Here, an organic solution with the passivation effect is prepared in situ by a non‐vacuum spraying process, which effectively compensates the cutting loss caused by laser slicing technology. Both the open‐circuit voltage (Voc) and power conversion efficiency (PCE) are improved. For example, after edge passivation, the Voc and PCE of the 3 × 3 cm2 SHJ (K = 1.186%) cell increase by up to 8 mV and a 1–2% in absolute efficiency, respectively. This passivation‐solution based method can be easily integrated into the current production line and thus solve the issue of cutting loss in separated silicon solar cells. This study provides a new passivation technology to compensate the recombination loss on the edge surface caused by the cutting process in shingle solar panels.

Diverse defects in copper indium gallium diselenide solar cells cause nonradiative recombination losses and impair device performance. Here, an organic passivation scheme for surface and grain boundary defects is reported, which employs an organic passivation agent to infiltrate the copper indium gallium diselenide thin films. A transparent conductive passivating (TCP) film is then developed by incorporating metal nanowires into the organic polymer and used in solar cells. The TCP films have a transmittance of more than 90% in the visible and nearinfrared spectra and a sheet resistance of ~10.5 Ω/sq. This leads to improvements in the open-circuit voltage and the efficiency of the organic passivated solar cells compared with control cells and paves the way for novel approaches to copper indium gallium diselenide defect passivation and possibly other compound solar cells.

Background and objective The curative potential of various bronchoscopic treatments such as electric snare, carbon dioxide freezing, argon plasma coagulation (APC), Neudymium-dopted Yttrium Aluminium Garnet (Nd:YAG) laser and photodynamic therapy (PDT) for the treatment of intraluminal tumor has been administered previously, but this regimen is not common in the treatment of typical carcinoid. The aim of this study is to investigate the curative effects both in short-term and long-term of interventional bronchoscopy in the treatment of typical carcinoid. Methods We retrospectively reviewed the clinical data of typical carcinoid patients who were treated with interventional bronchoscopy for tumor suppression and they were hospitalized in the Emergency General Hospital from December 2010 to December 2020, and Wilcoxon rank sum test and chi-square test were used for analysis. Results A total of 32 patients were included, including 18 cases of preoperative bronchial artery embolization (embolization rate 56%, 95%CI: 31%-79%). The grade score of dyspnea decreased from before treatment to after treatment, and the difference was statistically significant [(1.44±1.03) score vs (0.25±0.58) score, P=0.003]; The degree of bronchial stenosis decreased from pre-treatment to post-treatment, and the difference was statistically significant [(87.50%±13.90%) vs (17.50%±6.83%), P