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This study investigates the relationship between text-to-speech (TTS) usage and item-by-item performance in the 2017 eighth-grade National Assessment of Educational Progress (NAEP) math assessment, focusing on students with disabilities (SWDs), English language learners (ELLs), and their general education (GE) peers. Results indicate that all students use TTS more for longer and more difficult math items as well as for multiple-choice or short-response formats. Among SWDs and GE students, lower math proficiency and higher perceived time pressure are linked to higher TTS usage. Moreover, among GE students, factors such as male gender, minority status, lower math persistence, and higher math interest and effort during testing contribute to higher TTS usage. TTS usage is positively associated with item performance for SWDs and ELLs who received extended time accommodations but not for those who did not receive such accommodations or for general education students. The study suggests that the time constraints of speeded digital assessments may limit the potential benefits of TTS for SWDs and ELLs in math problem-solving.

This study analyzed performance, process, and survey data of eighth graders with learning disabilities (LDs) who took the 2017 National Assessment of Educational Progress (NAEP) digital math test. Compared with students with LDs who did not receive extended time accommodations (ETAs), students with LDs who received and used ETA scored significantly higher on the test, whereas students with LDs who received but did not use ETA scored significantly lower on the test. In addition, students with LDs in the two ETA groups reported a lower level of perceived time pressure and a higher level of math interest and enjoyment than their peers who did not receive ETA. For students with LDs who received ETA, optimal performance was achieved with 50% additional time, while their peers who did not receive ETA typically performed best when utilizing most of their allotted time. The analysis of process data revealed that students with LDs who used ETA performed more actions, had a higher number of revisits, used universal design digital tools more frequently, and performed better on time-consuming items than their peers who did not receive ETA at the same level of math performance.

Abstract Background Postoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD. Methods Herein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1. Results Based on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-α and IL-1β in the serum, increased levels of TNF-α and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-α in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-α, IL-1β and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus. Conclusions Our findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD.

Background In recent years, physical impairment (PI) combined with cognitive impairment (CI) is a common comorbidity in the elderly. An early detection of PI combined with CI in the elderly and timely interventions may help to improve the quality of life of the elderly and reduce the burden on their families and society. However, relevant studies on the comorbidity of PI and CI in the elderly and its influencing factors have been rarely reported. Objective To observe the clinical characteristics of the comorbidity of PI and CI in the elderly and the influencing factors. Methods Elderly patients hospitalized in Peking University People's Hospital from September 2018 to November 2019 were selected. A total of eligible 244 subjects meeting the inclusion criteria were surveyed for the physical function and cognitive function using the Short Physical Performance Battery (SPPB) and the Mini-mental State Examination (MMSE), respectively. PI was diagnosed with lower than 10 points of the SPPB, and CI was diagnosed with lower than 27 points of the MMSE. Patients were divided into non-PI+non-CI, PI+non-CI, non-PI+CI, PI+CI. Social demographic, anthropometric, laboratory examination and other indicators of patients were collected, and Logistic regression analysis was used to explore the influencing factors for PI combined with CI in the elderly. Results Among the 244 patients, there were 102 (41.80%), 64 (26.23%), 26 (10.66%) and 52 (21.31%) cases of non-PI+non-CI, PI+non-CI, non-PI+CI and PI+CI, respectively. Multivariate binary Logistic regression analysis showed that compared with non-PI+non-CI cases, age (P

Background: Benign prostate hyperplasia (BPH) occurs in elder men globally with high prevalence. Human diet and lifestyle aroused great attention in the prevalence of BPH. Prostate enlargement (PE) is a major symptom of BPH. Objectives: To elaborate the effect of total diet quality for adults from the United States, we investigated the association between Health Eating Index (HEI)-2015 and the risk of PE in adults from the National Health and Nutrition Examination Survey (NHANES). Methods: This cross-sectional study was conducted based on NHANES 2001–2008. Participants who reported a PE history were included. We conducted a logistic regression analysis to investigate the association between HEI-2015 and PE. Results: A total of 4,866 male participants aged 40 and above were enrolled. Compared with Q1 of HEI-2015, no significant differences were found in adjusted models. Higher vegetables intake (Odds ratio [OR] = 1.073; 95% confidence interval [95%CI] 1.015 to 1.134, P = 0.02) and higher total dairy intake (OR = 1.034; 95%CI 1.009 to 1.061, P = 0.01) were significantly related with higher risk of PE. Conclusions: There was no significant difference between HEI-2015 and PE after full adjustment. Total vegetables and dairy product might be associated with higher risk of PE and needed further validation.

Abstract Intrahepatic cholangiocarcinoma (iCCA) presents a challenging diagnosis due to its nonspecific early clinical manifestations, often resulting in late-stage detection and high mortality. Diagnosing iCCA is further complicated by its limited accuracy, often necessitating multiple invasive procedures for precise identification. Despite carbohydrate antigen 19–9 (CA19-9) having been investigated and employed for iCCA diagnosis, it demonstrates modest diagnostic performance. Consequently, the identification of novel biomarkers with improved sensitivity and specificity remains an imperative yet formidable task. Autoantibodies, as early indicators of the immune response against cancer, offer a promising avenue for enhancing diagnostic accuracy. Our study aimed to identify non-invasive blood-based autoantibody biomarkers capable of distinguishing iCCA patients from healthy individuals (CTRs). We profiled autoantibodies in 26 serum samples (16 iCCAs and 10 CTRs) using protein microarrays containing 1622 functional proteins. Leveraging machine learning techniques, we identified a signature composed of three autoantibody biomarkers (NDE1, PYCR1, and VIM) in conjunction with CA19-9 for iCCA detection. This combined signature demonstrated superior diagnostic performance with an AUC of 96.9%, outperforming CA19-9 alone (AUC: 83.8%). These results suggest the potential of autoantibody biomarkers to develop a complementary non-invasive diagnostic utility for routine iCCA screening.

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare cause of heart attack, which may not receive sufficient attention from patients during post-discharge treatment, especially among those with normal coronary angiography results. Case presentation We present the case of a 65-year-old woman who was readmitted to the hospital with ventricular septal rupture (VSR) complicated by ventricular aneurysm, occurring 2 weeks after myocardial infarction. During the initial admission, coronary angiography revealed normal coronary arteries, leading to a diagnosis of MINOCA. Epicardial coronary vasospasm or coronary embolism was considered as potential causes; however, the patient did not adhere to standardized treatment upon initial discharge. The delayed VSR led to a decline in cardiac function but did not result in severe hemodynamic impairment. Following correction of heart failure with medications, the patient underwent percutaneous VSR repair 19 days after diagnosis and was discharged with a favorable recovery. Conclusions The occurrence of delayed VSR complicated with ventricular aneurysm in patients with MINOCA is rare, highlighting the possibility of serious complications in MINOCA cases. Both cardioprotective therapies and cause-targeted therapies are essential in the management of patients with MINOCA.

Abstract Cyanobacteria are important primary producers, contributing to 25% of the global carbon fixation through photosynthesis. They serve as model organisms to study the photosynthesis, and are important cell factories for synthetic biology. To enable efficient genetic dissection and metabolic engineering in cyanobacteria, effective and accurate genetic manipulation tools are required. However, genetic manipulation in cyanobacteria by the conventional homologous recombination-based method and the recently developed CRISPR-Cas gene editing system require complicated cloning steps, especially during multi-site editing and single base mutation. This restricts the extensive research on cyanobacteria and reduces its application potential. In this study, a highly efficient and convenient cytosine base editing system was developed which allows rapid and precise C → T point mutation and gene inactivation in the genomes of Synechocystis and Anabaena. This base editing system also enables efficient multiplex editing and can be easily cured after editing by sucrose counter-selection. This work will expand the knowledge base regarding the engineering of cyanobacteria. The findings of this study will encourage the biotechnological applications of cyanobacteria.

In order to improve the yield of jackfruit peel pectin (JFPP) and obtain high-purity pectin with good functional properties, this study optimized the extraction process of pectin by ultrasound-assisted cellulase enzyme method through response surface experiments. The extracted pectin was preliminarily purified, including degreasing, deproteinization, decolorization, and dialysis concentration process. The purified pectin was then enzymatically esterified and modified by de-esterification to obtain de-esterified jackfruit peel pectin (DE-JFPP), and a comparative analysis was conducted on the basic composition, molecular weight, monosaccharide composition, functional group characteristics, thermal stability, and microstructure of the pectin before and after modification. The results showed that the optimal conditions for the extraction process were enzyme dosage of 0.7%, the enzymatic hydrolysis temperature of 30.4 ℃, and the pH of 4.6. It was observed that the yield of JFPP was 15.26%±0.07% under the specified conditions. The galacturonic acid content in the modified pectin increased from 79.10% to 83.24%, with a decrease in total sugar content from 43.42% to 41.90%, a decrease in esterification degree from 84.25% to 32.36%, and a decrease in weight-average molecular weight from 29.24 ku to 28.49 ku. Both JFPP and DE-JFPP contained eleven monosaccharides and belonged to the RG-I pectin with a decrease in the degree of branching in DE-JFPP. Fourier transform infrared (FTIR) spectroscopy demonstrated that both the pectin before and after modification had characteristic absorption peaks of pectin, and the peak area corresponding to the esterified carboxyl acid group decreased after modification. The JFPP and DE-JFPP demonstrated high thermal stability, with solubilization temperatures of 160.22 ℃ and 123.28 ℃, and degradation temperatures of 255.11 ℃ and 230.56 ℃, respectively. Scanning electron micrographs (SEM) showed that JFPP had a smooth surface and a compact structure, and DE-JFPP had a rough surface and a loose structure. This study optimized the extraction process of jackfruit peel pectin, improving its yield. Results demonstrated that the esterified pectin had favorable physicochemical properties and microstructure, meeting requirements for gel carrier systems in various fields and expanding the utilization space of jackfruit peel pectin.

Abstract Objective To test the glycemic susceptibility in three urological cancers and eight urological/reproductive diseases using the Mendelian randomization (MR) method. Materials and methods Two-sample MR was applied to investigate the causal role of three glycemic traits (type II diabetes, fasting glucose and glycated hemoglobin (HbA1c)) in eleven urological/reproductive diseases (kidney cancer, bladder cancer, prostate cancer, kidney/ureter stone, urinary incontinence, benign prostatic hyperplasia, erectile dysfunction, female infertility, male infertility, abnormal spermatozoa and polycystic ovary syndrome). Further multivariate MR (MVMR) and mediating analysis were performed to investigate the associations. Results Among all the 11 diseases, type II diabetes was positively associated with erectile dysfunction, which was stable across both cohorts [odds ratio (OR): 1.59, 95% confidence interval (CI): 1.15–2.20, P = 0.005 for FinnGen Biobank and OR: 1.14, 95% CI: 1.08–1.21, P

Abstract Immunotherapy exhibits considerable promise for sustained tumor reduction. However, current cancer immunotherapy methods elicit limited responses due to the inadequate immunogenicity exhibited by cancer cells. This obstacle may be addressed using nanoplatforms that can activate synergistic therapies (photodynamic therapy and ferroptosis) in response to the acidic pH of the tumor microenvironment. We previously developed an amphiphilic photosensitizer, SR780, which displays satisfactory photodynamic effects. This photosensitizer is inactivated when bound to Fe3+ (SR780Fe) but is activated upon release in mildly acidic conditions. In this study, M1 macrophage-derived extracellular vesicles (EVs) were fused with REV and SR780Fe–loaded liposomes (REV@SR780Fe@Lip) to form REV@SR780Fe@LEV hybrid nanovesicles. Further modification with the RS17 peptide for tumor targeting enabled a combination of photodynamic therapy, ferroptosis, and cGAS-STING pathway activation, resulting in enhanced antitumor efficacy through a synergistic effect. Upon laser irradiation, REV@SR780Fe@LEV-RS17 demonstrated antitumor effects in 4T1 breast cancer models, including the inhibition of lung and liver metastasis, as well as prevention of tumor recurrence. Graphical Abstract

In BCR-ABL1 lymphoblastic leukemia, treatment heterogeneity to tyrosine kinase inhibitors (TKIs), especially in the absence of kinase domain mutations in BCR-ABL1, is poorly understood. Through deep molecular profiling, we uncovered three transcriptomic subtypes of BCR-ABL1 lymphoblastic leukemia, each representing a maturation arrest at a stage of B-cell progenitor differentiation. An earlier arrest was associated with lineage promiscuity, treatment refractoriness and poor patient outcomes. A later arrest was associated with lineage fidelity, durable leukemia remissions and improved patient outcomes. Each maturation arrest was marked by specific genomic events that control different transition points in B-cell development. Interestingly, these events were absent in BCR-ABL1+ preleukemic stem cells isolated from patients regardless of subtype, which supports that transcriptomic phenotypes are determined downstream of the leukemia-initialing event. Overall, our data indicate that treatment response and TKI efficacy are unexpected outcomes of the differentiation stage at which this leukemia transforms.

Background: The senescence of endothelial cells is of great importance involving in atherosclerosis (AS) development. Recent studies have proved the protective role of mesenchymal stem cell-derived extracellular vesicles in AS, herein, we further desired to unvei their potential regulatory mechanisms in endothelial cell senescence. Methods: Senescence induced by H2O2 in primary mouse aortic endothelial cells (MAECs) was evaluated by SA-β-gal staining. Targeted molecule expression was detected by qRT-PCR and Western blotting. The biological functions of MAECs were determined by CCK-8, flow cytometry, transwell, and tube formation assays. Oxidative injury was assessed by LDH, total and lipid ROS, LPO and MDA levels. The proliferation of adipose-derived mesenchymal stem cell (ADSCs) was analyzed by EdU assay. Effect of ADSCs-derived extracellular vesicles (ADSC-EVs) on AS was investigated in HFD-fed ApoE−/− mice. Results: miR-674-5p was up-regulated, while C1q/TNF-related protein 9 (CTRP9) was down-regulated in H2O2-induced senescent MAECs. CTRP9 was demonstrated as a target gene of miR-674-5p. miR-674-5p inhibition restrained senescence, oxidative stress, promoted proliferation, migration, and angiogenesis of H2O2-stimulated MAECs via enhancing CTRP9 expression. Moreover, treatment with ADSC-EVs inhibited H2O2-induced senescence and dysfunction of MAECs through regulating miR-674-5p/CTRP9 axis. In the in vivo AS mouse model, ADSC-EVs combination with miR-674-5p silencing slowed down AS progression via up-regulation of CTRP9. Conclusion: ADSC-EVs repressed endothelial cell senescence and improved dysfunction via promotion of CTRP9 expression upon miR-674-5p deficiency during AS progression, which might provide vital evidence for ADSC-EVs as a promising therapy for AS.

Verticillium dahliae causes significant losses in cotton production. To reveal the mechanism of the defense response to V. dahliae in cotton, transcriptomic analyses were performed using cotton cultivars M138 (V. dahliae-resistant) and P2 (V. dahliae-susceptible). The results revealed 11,076 and 6,640 differentially expressed genes (DEGs) in response to V. dahliae, respectively. The weighted gene co-expression network analysis of 4,633 transcription factors (TFs) indicated a “MEblue” module containing 654 TFs that strongly correlate with resistance to V. dahliae. Among these TFs, the ethylene response factor Ghi_A05G10166 (GhERF91) was identified as a putative hub gene with a defense response against V. dahliae. A virus-induced gene silencing assay and exogenous application of ethephon showed that GhERF91 is activated by ethylene and positively regulates the response to V. dahliae exposure in cotton. This study provides fundamental transcriptome data and a putative causal gene (GhERF91) associated with resistance to V. dahliae, as well as genetic resources for breeding V. dahliae-resistant cotton.