Characteristics of Speech Auditory Brainstem Response in Preschool Children With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: This study aimed to investigate the characteristics of auditory processing (AP) in preschool children with attention-deficit/hyperactivity disorder (ADHD) using the speech auditory brainstem response (speech-ABR), which provides insights into the AP of speech signals in the central auditory nervous system (CANS). METHOD: A total of 84 preschool children diagnosed with ADHD, aged 4-6 years, were matched with 84 typically developing (TD) children based on gender and age. All children underwent speech-ABR testing, cognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition or the Wechsler Intelligence Scale for Children-Fourth Edition, and a continuous performance test. RESULTS: Children with ADHD exhibited significantly longer latencies of speech-ABR waveforms V, A, and D compared to TD children. Multiple linear regression analysis showed that the latencies of speech-ABR waves V, A, and D were affected by the presence of ADHD, but not by the full-scale intelligence quotient. CONCLUSIONS: This study revealed that preschool children with ADHD exhibited abnormal AP of speech signals in their CANS. The findings suggest that speech-ABR can be utilized as a reliable measure to evaluate AP ability in this population, as it remains unaffected by cognitive or attentional factors. The transient response (V, A) of speech-ABR was found to be a significant predictor of ADHD in a clinical setting. Early assessment of AP abnormalities via speech-ABR is recommended in preschool-age children to develop targeted interventions for ADHD. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26376502.

The potential use of microalgae for nutrient supply and health enhancement in isolated and confined environments.

Exploring isolated and confined environments (IACEs), such as deep-sea ecosystems, polar regions, and outer space, presents multiple challenges. Among these challenges, ensuring sustainable food supply over long timescales and maintaining the health of personnel are fundamental issues that must be addressed. Microalgae, as a novel food resource, possess favorable physiological and nutritional characteristics, demonstrating potential as nutritional support in IACEs. In this review, we discuss the potential of microalgae as a nutritional supplement in IACEs from four perspectives. The first section provides a theoretical foundation by reviewing the environmental adaptability and previous studies in IACEs. Subsequently, the typical nutritional components of microalgae and their bioavailability are comprehensively elucidated. And then focus on the impact of these ingredients on health enhancement and elucidate its mechanisms in IACEs. Combining the outstanding stress resistance, rich active ingredients, the potential to alleviate osteoporosis, regulate metabolism, and promote mental well-being, microalgae demonstrate significant value for food applications. Furthermore, the development of novel microalgae biomatrices enhances health safeguards. Nevertheless, the widespread application of microalgae in IACEs still requires extensive studies and more fundamental data, necessitating further exploration into improving bioavailability, high biomass cultivation methods, and enhancing palatability.

Clinicopathological features and prognosis of IgA vasculitis nephritis with nephrotic-range proteinuria in children.

BACKGROUND: To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children. METHODS: A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed. RESULTS: A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury. CONCLUSIONS: Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients.

Association between neural prosody discrimination and language abilities in toddlers: a functional near-infrared spectroscopy study.

BACKGROUND: Language delay affects near- and long-term social communication and learning in toddlers, and, an increasing number of experts pay attention to it. The development of prosody discrimination is one of the earliest stages of language development in which key skills for later stages are mastered. Therefore, analyzing the relationship between brain discrimination of speech prosody and language abilities may provide an objective basis for the diagnosis and intervention of language delay. METHODS: In this study, all cases(n = 241) were enrolled from a tertiary women's hospital, from 2021 to 2022. We used functional near-infrared spectroscopy (fNIRS) to assess children's neural prosody discrimination abilities, and a Chinese communicative development inventory (CCDI) were used to evaluate their language abilities. RESULTS: Ninety-eight full-term and 108 preterm toddlers were included in the final analysis in phase I and II studies, respectively. The total CCDI screening abnormality rate was 9.2% for full-term and 34.3% for preterm toddlers. Full-term toddlers showed prosody discrimination ability in all channels except channel 5, while preterm toddlers showed prosody discrimination ability in channel 6 only. Multifactorial logistic regression analyses showed that prosody discrimination of the right angular gyrus (channel 3) had a statistically significant effect on language delay (odd ratio = 0.301, P < 0.05) in full-term toddlers. Random forest (RF) regression model presented that prosody discrimination reflected by channels and brain regions based on fNIRS data was an important parameter for predicting language delay in preterm toddlers, among which the prosody discrimination reflected by the right angular gyrus (channel 4) was the most important parameter. The area under the model Receiver operating characteristic (ROC) curve was 0.687. CONCLUSIONS: Neural prosody discrimination ability is positively associated with language development, assessment of brain prosody discrimination abilities through fNIRS could be used as an objective indicator for early identification of children with language delay in the future clinical application.

A Full-Length Transcriptome and Analysis of the NHL-1 Gene Family in Neocaridina denticulata sinensis.

Neocaridina denticulata sinensis has emerged as a promising model organism for basic studies in Decapod. However, the current transcriptome information on this species is based on next-generation sequencing technologies, which are limited by a short read length. Therefore, the present study aimed to generate a full-length transcriptome assembly of N. denticulata sinensis utilizing the PacBio Sequel Ⅱ platform. The resulting transcriptome assembly comprised 5831 transcripts with an N50 value of 3697 bp. Remarkably, 90.5% of these transcripts represented novel isoforms of known genes. The transcripts were further searched against the NR, SwissProt, KEGG, KOG, GO, NT, and Pfam databases. A total of 24.8% of the transcripts can be annotated across all seven databases. Additionally, 1236 alternative splicing events, 344 transcription factors, and 124 long non-coding RNAs (LncRNAs) were predicted. Based on the alternative splicing annotation results, a RING finger protein NHL-1 gene from N. denticulata sinensis (NdNHL-1) was identified. There are 15 transcripts in NdNHL-1. The longest transcript is 4995 bp in length and encodes a putative protein of 1665 amino acids. A phylogenetic analysis showed its close relationship with NHL-1 from other crustacean species. This report represents the full-length transcriptome of N. denticulata sinensis and will facilitate research on functional genomics and environmental adaptation in this species.

Comparative transcriptomic analysis primarily explores the molecular mechanism of compound eye formation in Neocaridina denticulata sinensis.

Compound eyes formation in decapod crustaceans occurs after the nauplius stage. However, the key genes and regulatory mechanisms of compound eye development during crustacean embryonic development have not yet been clarified. In this study, RNA-seq was used to investigate the gene expression profiles of Neocaridina denticulata sinensis from nauplius to zoea stage. Based on RNA-seq data analysis, the phototransduction and insect hormone biosynthesis pathways were enriched, and molting-related neuropeptides were highly expressed. There was strong cell proliferation in the embryo prior to compound eye development. The formation of the visual system and the hormonal regulation of hatching were the dominant biological events during compound eye development. The functional analysis of DEGs across all four developmental stages showed that cuticle formation, muscle growth and the establishment of immune system occurred from nauplius to zoea stage. Key genes related to eye development were discovered, including those involved in the determination and differentiation of the eye field, eye-color formation, and visual signal transduction. In conclusion, the results increase the understanding of the molecular mechanism of eye formation in crustacean embryonic stage.

Membrane-bound trehalase enhances cadmium tolerance by regulating cell apoptosis in Neocaridina denticulata sinensis.

Trehalase gene is mainly expressed in the digestive circulatory system for regulating energy metabolism and chitin synthesis in insects, but it is significantly expressed in gill for immunomodulation in shrimp. However, its function in regulating immunity, particularly metal resistance in crustaceans has yet to be elucidated. In this study, one Tre2 gene (NdTre2) was isolated from Neocaridina denticulata sinensis. It could bind to Cd2+ and inhibit its toxicity. Spatiotemporal expression analysis showed that the expression of NdTre2 was highest in the gill and significantly reduced at 12 h after Cd2+ stimulation. The transcriptomic analysis of the gill after NdTre2 knockdown showed that the expression of genes synthetizing 20E was up-regulated and the increased 20E could further induce apoptosis by activating the intrinsic mitochondrial pathway, exogenous death receptor-ligand pathway, and MAPK pathway. In vitro, overexpressing NdTre2 enhanced the tolerance of E. coli in Cd2+ environment. In summary, these results indicate that NdTre2 plays an essential role in regulating immunity and chitin metabolism in N. denticulata sinensis.

Risk of secondary autoimmune diseases with alemtuzumab treatment for multiple sclerosis: a systematic review and meta-analysis.

Background and purpose: The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis. Methods: PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test. Results: The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02). Conclusion: The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment. Systematic review registration: inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.

Liquid crystalline elastomer self-oscillating fiber actuators fabricated from soft tubular molds.

The self-oscillation of objects that perform continuous and periodic motions upon unchanging and constant stimuli is highly important for intelligent actuators, advanced robotics, and biomedical machines. Liquid crystalline elastomer (LCE) materials are superior to traditional stimuli-responsive polymeric materials in the development of self-oscillators because of their reversible, large and anisotropic shape-changing ability, fast response ability and versatile structural design. In addition, fiber-shaped oscillators have attracted much interest due to their agility, flexibility and diverse oscillation modes. Herein, we present a strategy for fabricating fiber-shaped LCE self-oscillators using soft tubes as molds. Through the settlement of different configuration states of the soft tubes, the prepared fiber-shaped LCE oscillators can perform continuous rotational self-oscillation or up-and-down shifting self-oscillation under constant light stimuli, which are realized by photoinduced repetitive self-winding motion and self-waving motion, respectively. The mechanism of self-oscillating movements is attributed to the local temperature oscillation of LCE fibers caused by repetitive self-shadowing effects. LCE self-oscillators can operate stably over many oscillating cycles without obvious performance attenuation, revealing good robustness. Our work offers a versatile way by which LCE self-oscillators can be conveniently designed and fabricated in bulk and at low cost, and broadens the road for developing self-oscillating materials for biological robotics and health care machines.

Risk of secondary immune thrombocytopenia following alemtuzumab treatment for multiple sclerosis: a systematic review and meta-analysis.

Object: The purpose of this study was to evaluate the risk of secondary immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab through a meta-analysis. Methods: We searched databases including PubMed, Web of Science, OVID and EMBASE for studies reporting changes in platelet levels in MS patients treated with alemtuzumab from their inception until May 2023 and performed a meta-analysis. Information and data were screened and extracted by two researchers. The inclusion and exclusion criteria were established according to the PICOS principle. The obtained data were analyzed using the R software meta package and the quality assessment was conducted using Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger test. Results: A total of 15 studies were included, encompassing 1,729 multiple sclerosis patients. Meta-analysis of overall secondary ITP in the included studies yielded a pooled rate of 0.0243. The overall incidence of secondary autoimmune events was 0.2589. In addition, subgroup analysis was applied using study regions and study types. The results showed that the incidence rate of secondary ITP in Europe was about 0.0207, while the incidence of autoimmune events (AEs) was 0.2158. The incidence rate of secondary ITP and AEs in North America was significantly higher than in Europe, being 0.0352 and 0.2622. And the analysis showed that the incidence rates of secondary ITP and AEs in prospective studies were 0.0391 and 0.1771. Retrospective studies had an incidence rate of secondary ITP at 2.16, and an incidence rate of AEs at 0.2743. Conclusion: This study found that there was a certain incidence of Immune thrombocytopenia in multiple sclerosis patients after treatment with alemtuzumab. Alemtuzumab may have some interference with platelet levels, and the mechanism may be associated with Treg cells. But due to the absence of a control group in the included literature, we cannot determine the specific impact of Alemtuzumab on platelet levels in patients with MS. Therefore, clinical physicians should perform a comprehensive assessment of the patient's benefit-to-risk ratio before initiating alemtuzumab. Systematic Review Registration: Inplasy website, DOI number is 10.37766/inplasy2024.3.0007.

Bladder MRI with deep learning-based reconstruction: a prospective evaluation of muscle invasiveness using VI-RADS.

PURPOSE: To investigate the influence of deep learning reconstruction (DLR) on bladder MRI, specifically examination time, image quality, and diagnostic performance of vesical imaging reporting and data system (VI-RADS) within a prospective clinical cohort. METHODS: Seventy participants with bladder cancer who underwent MRI between August 2022 and February 2023 with a protocol containing standard T2-weighted imaging (T2WIS), standard diffusion-weighted imaging (DWIS), fast T2WI with DLR (T2WIDL), and fast DWI with DLR (DWIDL) were enrolled in this prospective study. Imaging quality was evaluated by measuring signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and qualitative image quality scoring. Additionally, the apparent diffusion coefficient (ADC) of bladder lesions derived from DWIS and DWIDL was measured and VI-RADS scoring was performed. Paired t-test or paired Wilcoxon signed-rank test were performed to compare image quality score, SNR, CNR, and ADC between standard sequences and fast sequences with DLR. The diagnostic performance for VI-RADS was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Compared to T2WIS and DWIS, T2WIDL and DWIDL reduced the acquisition time from 5:57 min to 3:13 min and showed significantly higher SNR, CNR, qualitative image quality score of overall image quality, image sharpness, and lesion conspicuity. There were no significant differences in ADC and AUC of VI-RADS between standard sequences and fast sequences with DLR. CONCLUSIONS: The application of DLR to T2WI and DWI reduced examination time and significantly improved image quality, maintaining ADC and the diagnostic performance of VI-RADS for evaluating muscle invasion in bladder cancer.

Comparative efficacy and safety between endoscopic submucosal dissection, surgery and definitive chemoradiotherapy in patients with cT1N0M0 esophageal cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) and surgical resection are the standard of care for cT1N0M0 esophageal cancer (EC), whereas definitive chemoradiotherapy (d-CRT) is a treatment option. Nevertheless, the comparative efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC remain unclear. AIM: To compare the efficiency and safety of ESD, surgery and d-CRT for cT1N0M0 EC. METHODS: We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th, 2022. We analyzed demographic, medical recorded, histopathologic characteristics, imaging and endoscopic, and follow-up data. The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments. Inverse probability of treatment weighting (IPTW) was used to minimize potential confounding factors. RESULTS: We retrospectively analyzed patients who underwent ESD (n = 99) or surgery (n = 220) or d-CRT (n = 16) at the Sun Yat-sen University Cancer Center from 2017 to 2019. The median follow-up time for the ESD group, the surgery group, and the d-CRT group was 42.0 mo (95%CI: 35.0-60.2), 45.0 mo (95%CI: 34.0-61.75) and 32.5 mo (95%CI: 28.3-40.0), respectively. After adjusting for background factors using IPTW, the highest 3-year overall survival (OS) rate and 3-year recurrence-free survival (RFS) rate were observed in the ESD group (3-year OS: 99.7% and 94.7% and 79.1%; and 3-year RFS: 98.3%, 87.4% and 79.1%, in the ESD, surgical, and d-CRT groups, respectively). There was no difference of severe complications occurring between the three groups (P ≥ 0.05). Multivariate analysis showed that treatment method, histology and depth of infiltration were independently associated with OS and RFS. CONCLUSION: For cT1N0M0 EC, ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery, with a similar rate of severe complications occurring.

[Association between auditory processing and problem behaviors in preschool children: the mediating role of executive function]. / å¬å¤„ç†ä¸Žå­¦é¾„å‰å„¿ç«¥é—®é¢˜è¡Œä¸ºçš„å ³ç³»ï¼šæ‰§è¡ŒåŠŸèƒ½çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To investigate the association between auditory processing and problem behaviors in preschool children, as well as the mediating role of executive function. METHODS: A total of 2 342 preschool children were selected from 7 kindergartens in Nanjing, China from June to August 2021. They were evaluated using Preschool Auditory Processing Assessment Scale, Conners Parent Symptom Questionnaire, and Behavior Rating Inventory of Executive Functioning-Preschool version. Children with different demographic features were compared in the scores and the abnormality rates of auditory processing, problem behaviors, and executive function. The influencing factors of the total scores of auditory processing, problem behaviors, and executive function were evaluated using multiple linear regression analysis. Whether executive function was a mediating factor between auditory processing and executive function was examined. RESULTS: Sex and grade were the main influencing factors for the total score of auditory processing (P<0.05), and sex, grade, parental education level, and family economic status were the main influencing factors for the total scores of problem behaviors and executive function (P<0.05). The auditory processing score (rs=0.458, P<0.05) and problem behavior score (rs=0.185, P<0.05) were significantly positively correlated with the executive function score, and the auditory processing score was significantly positively correlated with the problem behavior score (rs=0.423, P<0.05). Executive function played a partial mediating role between auditory processing and problem behaviors, and the mediating effect accounted for 33.44% of the total effect. CONCLUSIONS: Auditory processing can directly affect the problem behaviors of preschool children and indirectly affect problem behaviors through executive function.

An innovative lab-scale production for a novel therapeutic DNA vaccine candidate against rheumatoid arthritis.

BACKGROUND: Recent therapeutic-plasmid DNA vaccine strategies for rheumatoid arthritis (RA) have significantly improved. Our pcDNA-CCOL2A1 vaccine is the most prominent and the first antigen-specific tolerising DNA vaccine with potent therapeutic and prophylactic effects compared with methotrexate (MTX), the current "gold standard" treatment for collagen-induced arthritis (CIA). This study developed a highly efficient, cost-effective, and easy-to-operate system for the lab-scale production of endotoxin-free supercoiled plasmids with high quality and high yield. Based on optimised fermentation culture, we obtained a high yield of pcDNA-CCOL2A1 vaccine by PEG/MgCl2 precipitation and TRION-114. We then established a method for quality control of the pcDNA-CCOL2A1 vaccine. Collagen-induced arthritis (CIA) model rats were subjected to intramuscular injection of the pcDNA-CCOL2A1 vaccine (300 µg/kg) to test its biological activity. RESULTS: An average yield of 11.81 ± 1.03 mg purified supercoiled plasmid was obtained from 1 L of fermentation broth at 670.6 ± 57.42 mg/L, which was significantly higher than that obtained using anion exchange column chromatography and a commercial purification kit. Our supercoiled plasmid had high purity, biological activity, and yield, conforming to the international guidelines for DNA vaccines. CONCLUSION: The proposed innovative downstream process for the pcDNA-CCOL2A1 vaccine can not only provide a large-scale high-quality supercoiled plasmid DNA for preclinical research but also facilitate further pilot-scale and even industrial-scale production of pcDNA-CCOL2A1 vaccine.

Multi-omics analysis of disulfidptosis regulators and therapeutic potential reveals glycogen synthase 1 as a disulfidptosis triggering target for triple-negative breast cancer.

Disruption of disulfide homeostasis during biological processes can have fatal consequences. Excess disulfides induce cell death in a novel manner, termed as "disulfidptosis." However, the specific mechanism of disulfidptosis has not yet been elucidated. To determine the cancer types sensitive to disulfidptosis and outline the corresponding treatment strategies, we firstly investigated the crucial functions of disulfidptosis regulators pan-cancer at multi-omics levels. We found that different tumor types expressed dysregulated levels of disulfidptosis regulators, most of which had an impact on tumor prognosis. Moreover, we calculated the disulfidptosis activity score in tumors and validated it using multiple independent datasets. Additionally, we found that disulfidptosis activity was correlated with classic biological processes and pathways in various cancers. Disulfidptosis activity was also associated with tumor immune characteristics and could predict immunotherapy outcomes. Notably, the disulfidptosis regulator, glycogen synthase 1 (GYS1), was identified as a promising target for triple-negative breast cancer and validated via in vitro and in vivo experiments. In conclusion, our study elucidated the complex molecular phenotypes and clinicopathological correlations of disulfidptosis regulators in tumors, laying a solid foundation for the development of disulfidptosis-targeting strategies for cancer treatment.

PIWI-interacting RNA-YBX1 inhibits proliferation and metastasis by the MAPK signaling pathway via YBX1 in triple-negative breast cancer.

Breast cancer is the second leading cause of death in women worldwide, with triple-negative breast cancer (TNBC) having the worst prognosis. Although there are numerous studies on TNBC, there is no effective treatment for it, and it is still a major problem today. Studies on PIWI-interacting RNAs (piRNAs) are increasing and investigating the mechanism of piRNAs in the proliferation and metastasis of TNBC may lead to new potential treatment targets. Here, we identified a novel piRNA, piR-YBX1, which was downregulated in TNBC compared to matched normal breast tissue. Overexpression of piR-YBX1 significantly inhibited the proliferation, migration, invasion ability of TNBC cells both in vivo and in vitro. Mechanistically, piR-YBX1 could bind directly to mRNA of Y-box binding protein 1 (YBX1) and overexpression of piR-YBX1 downregulated YBX1 in both mRNA and protein levels, while the function of piR-YBX1 could be partly rescued by overexpression of YBX1. In addition, YBX1 could bind to RAF1 which is the key molecule in the MAPK signaling pathway, and overexpression of piR-YBX1 inhibited the p-MEK and p-ERK1/2, which can be reverted by YBX1. In conclusion, our findings discovered that the piR-YBX1/YBX1/MAPK axis suppresses the proliferation and metastasis of TNBC and therefore piR-YBX1 has the potential to be an effective therapeutic agent for breast cancer.

Transformed Salmonella typhimurium SL7207/pcDNA-CCOL2A1 as an orally administered DNA vaccine.

The use of attenuated bacteria for oral delivery of DNA vaccines is a recent innovation. We designed and constructed the naked plasmid DNA vaccine pcDNA-CCOL2A1, which effectively prevented and treated a rheumatoid arthritis model by inducing immunotolerance. We aimed to ensure a reliable, controllable dosage of this oral DNA vaccine preparation and establish its stability. We transformed pcDNA-CCOL2A1 via electroporation into attenuated Salmonella typhimurium SL7207. A resistant plate assay confirmed the successful construction of the transformed strain of the SL7207/pcDNA-CCOL2A1 oral DNA vaccine. We verified its identification and stability in vitro and in vivo. Significant differences were observed in the characteristics of the transformed and blank SL7207 strains. No electrophoretic restriction patterns or direct sequencing signals were observed in the original extract of the transformed strain. However, target gene bands and sequence signals were successfully detected after PCR amplification. CCOL2A1 expression was detected in the ilea of BALB/c mice that were orally administered SL7207/pcDNA-CCOL2A1. The pcDNA-CCOL2A1 plasmid of the transformed strain was retained under the resistant condition, and the transformed strain remained stable at 4 °C for 100 days. The concentration of the strain harboring the pcDNA-CCOL2A1 plasmid was stable at 109 CFU/mL after 6-8 h of incubation. The results demonstrated that the transformed strain SL7207/pcDNA-CCOL2A1 can be expressed in vivo, has good stability, and may be used to prepare the oral DNA vaccine pcDNA-CCOL2A1 with a stable, controllable dosage and the capacity to provide oral immunization. This vehicle can effectively combine both oral immunotolerance and DNA vaccination.

Does environmental regulation affect analyst forecast bias? Evidence from China's Low-Carbon Pilot Policy.

This study investigates the impact of China's Low-Carbon Pilot Policy on analyst forecast behaviors. Using a staggered difference-in-difference approach, we find that the program reduced analyst forecast errors and divergence, as mandatory sustainability disclosures enable analysts to incorporate new information to improve forecast quality. The effect is concentrated in state-owned firms and manufacturing-oriented cities. Additional tests explore accounting information quality and investor attention as plausible channels. Overall, exploiting a major Chinese environmental regulation, we provide novel evidence that green policies can enhance transparency and capital market efficiency. The findings offer implications for regulators, investors, and managers as countries pursue climate change mitigation strategies.