Ultrasound-Based Grading of Carpal Tunnel Syndrome: A Comparative Study of Cross-Sectional Area and Shear Wave Elastography at Different Wrist Joint Angles.

OBJECTIVE: Carpal Tunnel Syndrome (CTS) is a prevalent neuropathy where accurate diagnosis is crucial for effective treatment planning. This study introduces a novel approach for CTS grading using ultrasound, specifically through the analysis of the cross-sectional area (CSA) and shear wave elastography (SWE) of the median nerve in various wrist positions. METHODS: Our research involved subjects from outpatient clinics, diagnosed with CTS through Nerve Conduction Studies (NCS), and a control group of healthy individuals. High-frequency ultrasound and SWE measurements were conducted in three wrist positions: straight, 45° extension, and 45° flexion. RESULTS: The key findings revealed significant differences in median nerve CSA and SWE values between the CTS and control groups across all wrist positions, with notable variances in SWE values correlating with wrist positioning. SWE demonstrated enhanced sensitivity and specificity in distinguishing between mild, moderate, and severe CTS, especially at 45° wrist flexion. In contrast, CSA measurements were limited in differentiating between the varying severity stages of CTS. CONCLUSIONS: The study concludes that SWE, particularly at 45° wrist flexion, provides a more precise diagnostic benchmark for CTS severity grading than CSA. This advancement in non-invasive diagnostic methodology not only aids in accurate CTS grading but also has significant implications in formulating tailored treatment strategies, potentially reducing the reliance on more invasive diagnostic methods like NCS. ADVANCEMENT IN KNOWLEDGE: This study marks a significant advancement in the ultrasound diagnosis of CTS. It particularly highlights the importance of applying SWE technology across various wrist joint angles, offering a new diagnostic benchmark. This discovery provides data support and additional insights for achieving an early consensus on ultrasound-based grading diagnosis of CTS.

Molecularly imprinted polymer gel with superior recognition and adsorption capacity for amphenicol antibiotics in food matrices.

A molecular-imprinted polymer (MIP) gel with high effective recognition of amphenicol antibiotics was synthesized for the first time based on layered double hydroxide (LDH) as the support and initiator, and functionalized ß-cyclodextrin (ß-CD) as the functional monomer. The synergistic effect of molecular imprinting recognition and ß-CD host-guest affinity enabled MIP gel to exhibit excellent selectivity (imprinted factors: 3.9-9.4) and high adsorption capacity (28.9-75.4 mg g-1) for amphenicol antibiotics. Different adsorption isotherms and kinetics models were followed, suggesting heterogeneous single-layer recognition and chemical adsorption. After 5 cycles of adsorption and desorption, the adsorption capacity of MIP gel retained above 83.6 %, demonstrating favorable reproducibility and stability. Under optimal conditions, the method validation showed a satisfactory limit of detection (5-10 µg L-1), good correlation (r2 > 0.9967), and respectable recovery (82.6-105.3 %). The MIP gel was applied to extract amphenicol antibiotics from food matrices, achieving recoveries in the range of 78.3-104.5 %. Importantly, the recognition mechanism was studied in detail using density functional theory. Therefore, the established method demonstrates high sensitivity and can be applied as a new tactic for detecting amphenicol antibiotics in food matrices.

Examining the effect of nudging on college students' behavioral engagement and willingness to participate in online courses.

Nudging is a subtle behavioral intervention that has been successful in various domains such as healthy eating and energy conservation, yet its application in mental health remains underexplored. This study examines the effect of nudging to increase engagement with online mental health resources in a university setting. We assigned 2539 first-year undergraduate and graduate students in China to either a nudging group, which received course information augmented with behavioral cues (including framing effects and social norms), or a control group, which received only basic course information. Outcomes measured included self-reported willingness to enroll, willingness to recommend enrollment, and actual enrollment actions. Results indicated that students in the nudging group demonstrated significantly higher engagement levels than those in the control group across all metrics. These findings suggest the potential of nudging strategies to effectively enhance college students' participation in online mental health education.

A pan-allelic human SIRPα-blocking antibody, ES004-B5, promotes tumor killing by enhancing macrophage phagocytosis and subsequently inducing an effective T-cell response.

As a major immune cell type in the tumor microenvironment, tumor-associated macrophages secrete suppressive factors that can inhibit antitumor immunity and promote tumor progression. One approach trying to utilize macrophages for immunotherapy has been to block the CD47-SIRPα axis, which mediates inhibitory signaling, to promote phagocytosis of tumor cells. Many CD47-targeted agents, namely, anti-CD47 antibodies and SIRPα fusion proteins, were associated with a diverse spectrum of toxicities that limit their use in clinical settings. Universal expression of CD47 also leads to a severe "antigen sink" effect of CD47-targeted agents. Given that the CD47 receptor, SIRPα, has a more restricted expression profile and may have CD47-independent functions, targeting SIRPα is considered to have distinct advantages in improving clinical efficacy with a better safety profile. We have developed ES004-B5, a potentially best-in-class pan-allelic human SIRPα-blocking antibody using hybridoma technology. ES004-B5 binds to major human SIRPα variants through a unique epitope with high affinity. By blocking CD47-induced inhibitory "don't-eat-me" signaling, ES004-B5 exerts superior antitumor activity in combination with anti-tumor-associated antigen antibodies in vitro and in vivo. Unlike CD47-targeted agents, ES004-B5 exhibits an excellent safety profile in nonhuman primates. ES004-B5 has potential to be an important backbone for SIRPα-based combination therapy and/or bispecific antibodies, which will likely overcome the limitations of CD47-targeted agents encountered in clinical settings.

Extracellular vesicles-derived long noncoding RNAs participated in benzene hematotoxicity by mediating apoptosis and autophagy.

Benzene is a common contaminant in the workplace and wider environment, which induces hematotoxicity. Our previous study has implicated that lncRNAs mediated apoptosis and autophagy induced by benzene. Nevertheless, the roles of extracellular vesicle(EVs)-derived lncRNAs in benzene toxicity are unknown. However, the role of EVs and EVs-derived lncRNAs in benzene-induced toxicity remains unclear. In this research, we explored the function of EVs and EVs-derived lncRNAs in cell-cell communication through benzene-induced apoptosis and autophagy. Our findings demonstrated that EVs derived from 1,4-BQ-treated cells treated cells and coculture with 1,4-BQ-treated cells enhanced apoptosis and autophagy via regulating the pathways of PI3K-AKT-mTOR and chaperone-mediated autophagy. Treating with GW4869 in 1,4-BQ-treated cells significantly inhibited EV secretion, which reduced apoptosis and autophagy. Furthermore, we identified a set of differentially expressed autophagy- and apoptosis-related lncRNAs using EVs-derived lncRNA sequencing. Among them, 8 candidate lncRNAs were upregulated in EVs derived from 1,4-BQ-treated cells, as determined by lncRNA sequencing and qRT-PCR. Importantly, these lncRNAs were also increased in the serum EVs of benzene-exposed workers. 1,4-BQ-treated cells released EVs that transfer differentially expressed lncRNAs, thereby inducing apoptosis and autophagy in the recipient cells. The above results support the hypothesis that EVs-derived lncRNAs participate in intercellular communication during benzene-induced hematotoxicity and function as potential biomarkers for risk assessment of benzene-exposed workers.

Membrane-anchored intracellular insulin receptor or insulin-like growth factor-1 receptor elicits ligand-independent downstream signaling.

Neurodegenerative diseases including glaucoma affect insulin signaling, and insulin treatment has been shown to reverse the neurodegenerative loss of dendritic complexity in retinal ganglion cells. Therefore, strategies for enhancing or maintaining insulin signaling are worth pursuing to establish new therapies for these diseases. In the present study, we generated constitutively active insulin receptor (F-iIR) and insulin-like growth factor-1 receptor (F-iIGF1R) using a system that forces membrane localization of the intracellular domains of these receptors by farnesylation. Immunohistochemistry and Western blot analysis revealed that F-iIR and F-iIGF1R caused the activation of ERK and AKT in the absence of ligands in vitro. Our results suggest that in vivo effects of F-iIR and F-iIGF1R on the progression of neurodegenerative diseases should be investigated in the future.

Baseline Performance of Ultrasound-Based Strategies in Breast Cancer Screening Among Chinese Women.

RATIONALE AND OBJECTIVE: There is a notable absence of robust evidence on the efficacy of ultrasound-based breast cancer screening strategies, particularly in populations with a high prevalence of dense breasts. Our study addresses this gap by evaluating the effectiveness of such strategies in Chinese women, thereby enriching the evidence base for identifying the most efficacious screening approaches for women with dense breast tissue. METHODS: Conducted from October 2018 to August 2022 in Central China, this prospective cohort study enrolled 8996 women aged 35-64 years, divided into two age groups (35-44 and 45-64 years). Participants were screened for breast cancer using hand-held ultrasound (HHUS) and automated breast ultrasound system (ABUS), with the older age group also receiving full-field digital mammography (FFDM). The Breast Imaging Reporting and Data System (BI-RADS) was employed for image interpretation, with abnormal results indicated by BI-RADS 4/5, necessitating a biopsy; BI-RADS 3 required follow-up within 6-12 months by primary screening strategies; and BI-RADS 1/2 were classified as negative. RESULTS: Among the screened women, 29 cases of breast cancer were identified, with 4 (1.3‰) in the 35-44 years age group and 25 (4.2‰) in the 45-64 years age group. In the younger age group, HHUS and ABUS performed equally well, with no significant difference in their AUC values (0.8678 vs. 0.8679, P > 0.05). For the older age group, ABUS as a standalone strategy (AUC 0.9935) and both supplemental screening methods (HHUS with FFDM, AUC 0.9920; ABUS with FFDM, AUC 0.9928) outperformed FFDM alone (AUC 0.8983, P < 0.05). However, there was no significant difference between HHUS alone and FFDM alone (AUC 0.9529 vs. 0.8983, P > 0.05). CONCLUSION: The findings indicate that both HHUS and ABUS exhibit strong performance as independent breast cancer screening strategies, with ABUS demonstrating superior potential. However, the integration of FFDM with these ultrasound techniques did not confer a substantial improvement in the overall effectiveness of the screening process.

Follicular fluid lipidomics analysis reveals altered lipid signatures in patients with polycystic ovary syndrome.

BACKGROUND: This research investigates the metabolic profiles of follicular fluid (FF) samples from patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilisation and aims to identify diagnostic and therapeutic biomarkers for PCOS through lipidomic analysis. METHODS: We performed non-targeted lipid analysis of FF samples from women with PCOS (n = 6) and normal controls (n = 6) using ultra-high-performance liquid chromatography-tandem mass spectrometry. Differential lipids between the two groups were screened using multidimensional statistical analysis, followed by fold change analysis and t-tests to identify potential PCOS biomarkers. RESULTS: Multivariate statistical analysis revealed significant differences in FF lipid levels between the PCOS and control groups. Five different lipids were selected as standards, with p < .05. Phosphatidylcholine (PC), the main differentially expressed lipid, was significantly increased in the FF of the POCS group and was closely related to other lipids. CONCLUSIONS: Using ultra-high-performance liquid chromatography-tandem mass spectrometry, we investigated lipid biomarkers based on FF lipidomics to provide useful information for the discovery of diagnostic markers for PCOS. Our study identified five distinct lipids as potential markers of PCOS, with PC being the primary aberrant lipid found in the FF of patients with PCOS.

Follicular fluid (FF) is a complex microenvironment involved in oocyte growth, follicular maturation and germ cell­somatic cell communication. All metabolites during oocyte growth are collected from the FF. This study used lipidomic analysis to identify differences in FF lipids between normal women and those diagnosed with polycystic ovary syndrome (PCOS). The pathogenesis of PCOS is associated with abnormal metabolism of glyceroglycolipids and sphingomyelin. Here, we found that phosphatidylcholine is the main abnormal lipid in FF in patients with PCOS. Our study informs the future research into the development of diagnostic markers for PCOS to be used in clinical practice.

Biportal Endoscopic Spinal Cord Stimulation Paddle Lead Implantation: Technical Note and Preliminary Clinical Results.

OBJECTIVE: This study aims to elucidate a novel, minimally invasive surgical technique using a biportal endoscope for the implantation of spinal cord stimulation (SCS) paddle leads and to report the preliminary results of its clinical application. MATERIALS AND METHODS: The perioperative data of patients who underwent the biportal endoscopic SCS paddle lead implantation in our department were collected; the surgical procedure was delineated, and the clinical outcomes were assessed. RESULTS: From February 2022 to December 2023, six patients underwent biportal endoscopic SCS paddle lead implantation. The median follow-up time was nine months (range one to three months). The median intraoperative blood loss was 30 mL (range 25-50 mL), and the median operative time was 87.5 minutes (range 75-110 minutes). One patient experienced severe neck pain during the operation, whereas the other five patients experienced no surgical complications. One patient was found to have a slight lead migration three months after surgery, which did not affect the therapeutic effect. The median visual analogue scale (VAS) of the surgical area was 0.5 (range 0-2), 2.5 (range 1-4), and 0.5 (range 0-1) during the operation and one day and one week after the operation, respectively. The median VAS of the six patients' primary disease was 8 (range 7-9) before surgery and 2.5 (range 1-4) at the last postoperative follow-up (pain reduction ≥50%). CONCLUSION: Paddle lead systems for SCS can be implanted successfully using a biportal endoscopic technique.

Soybean ethylene response factors GmENS1 and GmENS2 promote nodule senescence.

The final phase in root nodule development is nodule senescence. The mechanism underlying the initiation of nodule senescence requires further elucidation. In this study, we investigate the intrinsic signals governing soybean (Glycine max L. Merr.) nodule senescence, uncovering ethylene as a key signal in this intricate mechanism. Two AP2/ethylene response factor (ERF) transcription factor (TF) genes, GmENS1 and GmENS2 (Ethylene-responsive transcription factors required for Nodule Senescence), exhibit heightened expression levels in both aged nodules and nodules treated with ethylene. An overexpression of either GmENS1 or GmENS2 accelerates senescence in soybean nodules, whereas the knockout or knockdown of both genes delays senescence and enhances nitrogenase activity. Furthermore, our findings indicate that GmENS1 and GmENS2 directly bind to the promoters of GmNAC039, GmNAC018, and GmNAC030, encoding 3 NAC (NAM, ATAF1/2, and CUC2) TFs essential for activating soybean nodule senescence. Notably, the nodule senescence process mediated by GmENS1 or GmENS2 overexpression is suppressed in the soybean nac039/018/030 triple mutant compared with the wild-type control. These data indicate GmENS1 and GmENS2 as pivotal TFs mediating ethylene-induced nodule senescence through the direct activation of GmNAC039/GmNAC018/GmNAC030 expression in soybean.

Discovery and analysis of microplastics in human bone marrow.

The health implications of human exposure to microplastics (MPs) have raised significant concerns. While evidence indicates MPs can accumulate in closed human organs like the heart, placenta, and blood, there is no available data on MP exposure specifically within the human bone marrow. To fill the research gap, this study detected the concentration of microplastics (MPs) in bone marrow samples by pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) and assessed the size range and morphological characteristics of MPs by Laser Direct Infrared Spectroscopy (LD-IR) and scanning electron microscopy (SEM). Our study shows that MPs were present in all 16 bone marrow samples, with an average concentration of 51.29 µg/g ranging from 15.37 µg/g to 92.05 µg/g. Five polymer types-polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), polyadiohexylenediamine 66 (PA66), and polypropylene (PP), were identified. PE was the most frequent polymer detected in the bone marrow, with an average concentration of 30.02 µg/g ranging from 14.77 µg/g to 52.57 µg/g, with a detection rate of 93.75 %. PS had the highest detection rate at 100 % of bone marrow samples, while PVC and PA66 were found in 75 % of samples each. LD-IR analysis revealed the identification of 25 polymer types, with an average abundance of 19.72 particles/g. Of these, 89.82 % of the MPs were smaller than 100 µm. In summary, this study has, for the first time, demonstrated the presence of MPs are deeply embedded within human bone marrow, providing a basis for future investigations into their potential toxicological effects and underlying mechanisms affecting the hematopoietic system.

Rhamnolipids-based bio-supramolecular solvents as green and sustainable media for extraction of pyrethroid insecticides in water and food matrices.

A novel bio-supramolecular solvent (bio-SUPRAS) based on rhamnolipids (RLs) was designed for efficient extraction of pyrethroid insecticides in water and food matrices. Benefiting from RLs as amphiphiles equipped with the attractive properties of bio-degradable, low toxicity and high stability, bio-SUPRAS was spontaneously generated through salt induced coagulation. The bio-SUPRAS was characterized by cryo-scanning electron microscope and main factors influencing the extraction performance were investigated in detail. Under the optimized conditions, the method was found to have desirable limits of detection (5∼10 µg l-1), good precision (RSDs<16.9 %) and satisfactory recovery (75.2 %∼94.3 %). More importantly, the extraction mechanism was studied by density functional theory systematically. Following greenness assessment, the technique was successfully used for enrichment of pyrethroid pesticides in real samples before HPLC-UV analysis. Thus, the method showed the outstanding merits of eco-efficient, green, time-saving, and had favorable application prospect to remove trace analytes from intricate sample matrices.

Endophyte-mediated enhancement of salt resistance in Arachis hypogaea L. by regulation of osmotic stress and plant defense-related genes.

Introduction: Soil salinization poses a significant environmental challenge affecting plant growth and agricultural sustainability. This study explores the potential of salt-tolerant endophytes to mitigate the adverse effects of soil salinization, emphasizing their impact on the development and resistance of Arachis hypogaea L. (peanuts). Methods: The diversity of culturable plant endophytic bacteria associated with Miscanthus lutarioriparius was investigated. The study focused on the effects of Bacillus tequilensis, Staphylococcus epidermidis, and Bacillus siamensis on the development and germination of A. hypogaea seeds in pots subjected to high NaCl concentrations (200 mM L-1). Results: Under elevated NaCl concentrations, the inoculation of endophytes significantly (p < 0.05) enhanced seedling germination and increased the activities of enzymes such as Superoxide dismutase, catalase, and polyphenol oxidase, while reducing malondialdehyde and peroxidase levels. Additionally, endophyte inoculation resulted in increased root surface area, plant height, biomass contents, and leaf surface area of peanuts under NaCl stress. Transcriptome data revealed an augmented defense and resistance response induced by the applied endophyte (B. tequilensis, S. epidermidis, and B. siamensis) strain, including upregulation of abiotic stress related mechanisms such as fat metabolism, hormones, and glycosyl inositol phosphorylceramide (Na+ receptor). Na+ receptor under salt stress gate Ca2+ influx channels in plants. Notably, the synthesis of secondary metabolites, especially genes related to terpene and phenylpropanoid pathways, was highly regulated. Conclusion: The inoculated endophytes played a possible role in enhancing salt tolerance in peanuts. Future investigations should explore protein-protein interactions between plants and endophytes to unravel the mechanisms underlying endophyte-mediated salt resistance in plants.

Dynamic modulation of nodulation factor receptor levels by phosphorylation-mediated functional switch of a RING-type E3 ligase during legume nodulation.

The precise control of receptor levels is crucial for initiating cellular signaling transduction in response to specific ligands; however, such mechanisms regulating nodulation factor (NF) receptor (NFR)-mediated perception of NFs to establish symbiosis remain unclear. In this study, we unveil the pivotal role of the NFR-interacting RING-type E3 ligase 1 (NIRE1) in regulating NFR1/NFR5 homeostasis to optimize rhizobial infection and nodule development in Lotus japonicus. We demonstrated that NIRE1 has a dual function in this regulatory process. It associates with both NFR1 and NFR5, facilitating their degradation through K48-linked polyubiquitination before rhizobial inoculation. However, following rhizobial inoculation, NFR1 phosphorylates NIRE1 at a conserved residue, Tyr-109, inducing a functional switch in NIRE1, which enables NIRE1 to mediate K63-linked polyubiquitination, thereby stabilizing NFR1/NFR5 in infected root cells. The introduction of phospho-dead NIRE1Y109F leads to delayed nodule development, underscoring the significance of phosphorylation at Tyr-109 in orchestrating symbiotic processes. Conversely, expression of the phospho-mimic NIRE1Y109E results in the formation of spontaneous nodules in L. japonicus, further emphasizing the critical role of the phosphorylation-dependent functional switch in NIRE1. In summary, these findings uncover a fine-tuned symbiotic mechanism that a single E3 ligase could undergo a phosphorylation-dependent functional switch to dynamically and precisely regulate NF receptor protein levels.

Designing green and recyclable switchable supramolecular deep eutectic solvents for efficient extraction of flavonoids from Scutellariae Radix and mechanism exploration.

A green and recyclable switchable supramolecular deep eutectic solvent (SS-DES) was designed and prepared for effective extraction of flavonoids from Scutellariae Radix. The novel SS-DES has both excellent extraction performance of DES and the host guest inclusion of cyclodextrin, thereby showing superior extraction efficiency and selectivity. The characteristic of polarity switching can endow the SS-DES with achieving homogeneous extraction and rapid two-phase separation, shorting per-treatment time largely. Parameters affecting the extraction performance were investigated by the response surface methodology. The results indicated that the SS-DES showed better extraction yield of total flavonoids (157.95 mg/g) compared with pure DES (135 mg/g) and traditional organic solvent (60 % ethanol, 104.87 mg/g). Moreover, the switching mechanism of SS-DES was characterized by FT-IR and 1H NMR, and the extraction mechanism was studied by density functional theory and molecular docking analysis. After evaluating the ecological impact of the method, the cytotoxicity of SS-DES was investigated and the result displayed that its toxicity was very low or even negligible with the EC50>2000 mg/L. After being adsorbed by macroporous AB-8 resin, the regenerated SS-DES was recycled 5 times and the extraction efficiency still remained above 90 %, indicating the desirable reusability. Therefore, the proposed method was efficient and sustainable, and revealed favorable application prospect for the extraction of bio-active compounds from plant materials.

Mechanisms of hepatic steatosis in chickens: integrated analysis of the host genome, molecular phenomics and gut microbiome.

Hepatic steatosis is the initial manifestation of abnormal liver functions and often leads to liver diseases such as nonalcoholic fatty liver disease in humans and fatty liver syndrome in animals. In this study, we conducted a comprehensive analysis of a large chicken population consisting of 705 adult hens by combining host genome resequencing; liver transcriptome, proteome, and metabolome analysis; and microbial 16S ribosomal RNA gene sequencing of each gut segment. The results showed the heritability (h2 = 0.25) and duodenal microbiability (m2 = 0.26) of hepatic steatosis were relatively high, indicating a large effect of host genetics and duodenal microbiota on chicken hepatic steatosis. Individuals with hepatic steatosis had low microbiota diversity and a decreased genetic potential to process triglyceride output from hepatocytes, fatty acid ß-oxidation activity, and resistance to fatty acid peroxidation. Furthermore, we revealed a molecular network linking host genomic variants (GGA6: 5.59-5.69 Mb), hepatic gene/protein expression (PEMT, phosphatidyl-ethanolamine N-methyltransferase), metabolite abundances (folate, S-adenosylmethionine, homocysteine, phosphatidyl-ethanolamine, and phosphatidylcholine), and duodenal microbes (genus Lactobacillus) to hepatic steatosis, which could provide new insights into the regulatory mechanism of fatty liver development.